|
1
|
Pan Y, Yang Y, Peng Z, Wang W, Zhang J, Sun G, Wang F, Zhu Z, Cao H, Lyu Y, Zhang Z, Yang W. Gut microbiota may modify the association between dietary polyphenol intake and serum concentrations of hippuric acid: results from a 1-year longitudinal study in China. Am J Clin Nutr 2025:S0002-9165(25)00018-8. [PMID: 39837385 DOI: 10.1016/j.ajcnut.2025.01.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 01/06/2025] [Accepted: 01/15/2025] [Indexed: 01/23/2025] Open
Abstract
BACKGROUND Hippuric acid (HA), a host-microbe cometabolite, normally derives from gut microbial catabolism of dietary polyphenols. OBJECTIVES We investigated the potential interplay between dietary polyphenols and gut microbiota on circulating HA concentrations and examined the associations between serum concentrations of HA and cardiometabolic risk markers. METHODS In a 1-y cohort of 754 community-dwelling adults, serum HA and its precursor [benzoic acid (BA)], and fecal microbiota were assayed using liquid chromatography-tandem mass spectrometry and 16S ribosomal RNA sequencing, respectively. Diet, blood pressure, blood glucose, and lipid concentrations were measured twice, 1 y apart. Arterial stiffness [indicated by brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index] and liver fat accumulation [indicated by controlled attenuation parameter (CAP)] were measured after 1 y. RESULTS We identified 27 microbial genera whose relative abundance was positively associated with serum HA concentrations (PFDR < 0.05) and constructed a microbial score to reflect the overall HA-producing potential. In multivariate-adjusted linear models, dietary intake of catechins and chlorogenic acids was positively associated with serum HA concentrations among participants with a higher microbial score (β = 0.26, P = 0.03) but not among those with a lower score (β = -0.13, P = 0.30, Pinteraction = 0.03). Participants with higher intake of dietary catechins and chlorogenic acids had lower triglyceride concentrations (Percentage change = -5.9%, P < 0.05). Each 1 μmol/L increase in serum HA, but not in BA, was associated with 5.7%, 1.5%, 1.7%, 1.7%, and 1.7% decrease in triglyceride, systolic blood pressure, diastolic blood pressure, baPWV, and CAP, respectively (all P < 0.05). CONCLUSIONS The gut microbial genera that predicted circulating HA concentrations might modify the association between dietary polyphenol intake and circulating HA concentrations, and elevated serum HA concentrations are favorably associated with multiple cardiometabolic risk markers.
Collapse
Affiliation(s)
- Yutong Pan
- Department of Nutrition, Center for Big Data and Population Health of IHM, The Second Affiliated Hospital of Anhui Medical University, School of Public Health, Anhui Medical University, Hefei, China
| | - Yang Yang
- Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Zhaohong Peng
- Department of Interventional Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Wuqi Wang
- Department of Nutrition, Center for Big Data and Population Health of IHM, The Second Affiliated Hospital of Anhui Medical University, School of Public Health, Anhui Medical University, Hefei, China
| | - Junyi Zhang
- Department of Nutrition, Center for Big Data and Population Health of IHM, The Second Affiliated Hospital of Anhui Medical University, School of Public Health, Anhui Medical University, Hefei, China
| | - Guobing Sun
- Department of Nutrition, Center for Big Data and Population Health of IHM, The Second Affiliated Hospital of Anhui Medical University, School of Public Health, Anhui Medical University, Hefei, China
| | - Fuyu Wang
- Department of Nutrition, Center for Big Data and Population Health of IHM, The Second Affiliated Hospital of Anhui Medical University, School of Public Health, Anhui Medical University, Hefei, China
| | - Zixuan Zhu
- Department of Nutrition, Center for Big Data and Population Health of IHM, The Second Affiliated Hospital of Anhui Medical University, School of Public Health, Anhui Medical University, Hefei, China
| | - Hongjuan Cao
- Department of Chronic Non-communicable Diseases Prevention and Control, Lu'an Municipal Center for Disease Control and Prevention, Lu'an, China
| | - Young Lyu
- Department of Chronic Non-communicable Diseases Prevention and Control, Lu'an Municipal Center for Disease Control and Prevention, Lu'an, China
| | - Zhuang Zhang
- Department of Nutrition, Center for Big Data and Population Health of IHM, The Second Affiliated Hospital of Anhui Medical University, School of Public Health, Anhui Medical University, Hefei, China
| | - Wanshui Yang
- Department of Nutrition, Center for Big Data and Population Health of IHM, The Second Affiliated Hospital of Anhui Medical University, School of Public Health, Anhui Medical University, Hefei, China.
| |
Collapse
|
|
2
|
Li W, Dong H, Niu K, Wang HY, Cheng W, Song H, Ying AK, Zhai X, Li K, Yu H, Guo DS, Wang Y. Analyzing urinary hippuric acid as a metabolic health biomarker through a supramolecular architecture. Talanta 2024; 278:126480. [PMID: 38972275 DOI: 10.1016/j.talanta.2024.126480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 06/10/2024] [Accepted: 06/25/2024] [Indexed: 07/09/2024]
Abstract
The prevalence of metabolic disorders has been found to increase concomitantly with alternations in habitual diet and lifestyle, indicating the importance of metabolic health monitoring for early warning of high-risk status and suggesting effective intervention strategies. Hippuric acid (HA), as one of the most abundant metabolites from the gut microbiota, holds potential as a regulator of metabolic health. Accordingly, it is imperative to establish an efficient, sensitive, and affordable method for large-scale population monitoring, revealing the association between HA level and metabolic disorders. Upon systematic screening of macrocycle•dye reporter pair, a supramolecular architecture (guanidinomethyl-modified calix[5]arene, GMC5A) was employed to sense urinary HA by employing fluorescein (Fl), whose complexation behavior was demonstrated by theoretical calculations, accomplishing quantification of HA in urine from 249 volunteers in the range of 0.10 mM and 10.93 mM. Excitedly, by restricted cubic spline, urinary HA concentration was found to have a significantly negative correlation with the risk of metabolic disorders when it exceeded 0.76 mM, suggesting the importance of dietary habits, especially the consumption of fruits, coffee, and tea, which was unveiled from a simple questionnaire survey. In this study, we accomplished a high throughput and sensitive detection of urinary HA based on supramolecular sensing with the GMC5A•Fl reporter pair, which sheds light on the rapid quantification of urinary HA as an indicator of metabolic health status and early intervention by balancing the daily diet.
Collapse
Affiliation(s)
- Wenhui Li
- National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Hua Dong
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300193, China
| | - Kejing Niu
- National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Huan-Yu Wang
- College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), Frontiers Science Center for New Organic Matter, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin, 300071, China
| | - Wenqian Cheng
- National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Hualong Song
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300193, China
| | - An-Kang Ying
- College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), Frontiers Science Center for New Organic Matter, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin, 300071, China
| | - Xiaobing Zhai
- Faculty of Applied Sciences, Macao Polytechnic University, Macau, China
| | - Kefeng Li
- Faculty of Applied Sciences, Macao Polytechnic University, Macau, China
| | - Huijuan Yu
- National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China.
| | - Dong-Sheng Guo
- College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), Frontiers Science Center for New Organic Matter, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin, 300071, China.
| | - Yuefei Wang
- National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China.
| |
Collapse
|
|
3
|
Li J, O’Toole PW. Disease-associated microbiome signature species in the gut. PNAS NEXUS 2024; 3:pgae352. [PMID: 39228810 PMCID: PMC11370893 DOI: 10.1093/pnasnexus/pgae352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 08/12/2024] [Indexed: 09/05/2024]
Abstract
There is an accumulation of evidence that the human gut microbiota plays a role in maintaining health, and that an altered gut microbiota (sometimes called dysbiosis) associates with risk for many noncommunicable diseases. However, the dynamics of disease-linked bacteria in the gut and other body sites remain unclear. If microbiome alterations prove causative in particular diseases, therapeutic intervention may be possible. Furthermore, microbial signature taxa have been established for the diagnosis of some diseases like colon cancer. We identified 163 disease-enriched and 98 disease-depleted gut microbiome signature taxa at species-level resolution (signature species) from 10 meta-analyses of multiple diseases such as colorectal cancer, ulcerative colitis, Crohn's disease, irritable bowel syndrome, pancreatic cancer, and COVID-19 infection. Eight signature species were enriched and nine were depleted across at least half of the diseases studied. Compared with signature species depleted in diseases, a significantly higher proportion of disease-enriched signature species were identified as extra-intestinal (primarily oral) inhabitants, had been reported in bacteremia cases from the literature, and were aerotolerant anaerobes. These findings highlight the potential involvement of oral microbes, bacteremia isolates, and aerotolerant anaerobes in disease-associated gut microbiome alterations, and they have implications for patient care and disease management.
Collapse
Affiliation(s)
- Junhui Li
- APC Microbiome Ireland, University College Cork, Cork T12 K8AF, Ireland
- School of Microbiology, University College Cork, Cork T12 K8AF, Ireland
| | - Paul W O’Toole
- APC Microbiome Ireland, University College Cork, Cork T12 K8AF, Ireland
- School of Microbiology, University College Cork, Cork T12 K8AF, Ireland
| |
Collapse
|
|
4
|
Punzo A, Silla A, Fogacci F, Perillo M, Cicero AFG, Caliceti C. Bile Acids and Bilirubin Role in Oxidative Stress and Inflammation in Cardiovascular Diseases. Diseases 2024; 12:103. [PMID: 38785758 PMCID: PMC11119340 DOI: 10.3390/diseases12050103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 05/10/2024] [Accepted: 05/11/2024] [Indexed: 05/25/2024] Open
Abstract
Bile acids (BAs) and bilirubin, primarily known for their role in lipid metabolism and as heme catabolite, respectively, have been found to have diverse effects on various physiological processes, including oxidative stress and inflammation. Indeed, accumulating evidence showed that the interplay between BAs and bilirubin in these processes involves intricate regulatory mechanisms mediated by specific receptors and signaling pathways under certain conditions and in specific contexts. Oxidative stress plays a significant role in the development and progression of cardiovascular diseases (CVDs) due to its role in inflammation, endothelial dysfunction, hypertension, and other risk factors. In the cardiovascular (CV) system, recent studies have suggested that BAs and bilirubin have some opposite effects related to oxidative and inflammatory mechanisms, but this area of research is still under investigation. This review aims to introduce BAs and bilirubin from a biochemical and physiological point of view, emphasizing their potential protective or detrimental effects on CVDs. Moreover, clinical studies that have assessed the association between BAs/bilirubin and CVD were examined in depth to better interpret the possible link between them.
Collapse
Affiliation(s)
- Angela Punzo
- Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (A.P.); (M.P.); (C.C.)
- Biostructures and Biosystems National Institute (INBB), 00136 Rome, Italy
| | - Alessia Silla
- Department for Life Quality Studies, Alma Mater Studiorum, University of Bologna, 47921 Rimini, Italy;
| | - Federica Fogacci
- Hypertension and Cardiovascular Risk Research Center, Medical and Surgery Sciences Dept., Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy;
| | - Matteo Perillo
- Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (A.P.); (M.P.); (C.C.)
| | - Arrigo F. G. Cicero
- Hypertension and Cardiovascular Risk Research Center, Medical and Surgery Sciences Dept., Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy;
- Cardiovascular Medicine Unit, IRCCS AOU di Bologna, 40138 Bologna, Italy
| | - Cristiana Caliceti
- Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (A.P.); (M.P.); (C.C.)
- Biostructures and Biosystems National Institute (INBB), 00136 Rome, Italy
- Interdepartmental Centre for Industrial Agrofood Research—CIRI Agrofood, University of Bologna, 47521 Cesena, Italy
| |
Collapse
|
|
5
|
Lee NR, Kwon TJ, Chung EC, Bae J, Soung SH, Tak HJ, Choi JY, Lee YE, Won Hwang N, Lee JS, Shin KJ, Lee CH, Kim K, Kim S. Combination of Lacticaseibacillus paracasei BEPC22 and Lactiplantibacillus plantarum BELP53 attenuates fat accumulation and alters the metabolome and gut microbiota in mice with high-fat diet-induced obesity. Food Funct 2024; 15:647-662. [PMID: 38099933 DOI: 10.1039/d3fo03557c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2024]
Abstract
This study evaluated the effects of formulations with Lacticaseibacillus paracasei BEPC22 and Lactiplantibacillus plantarum BELP53 on adiposity, the alteration of microbiota, and the metabolome in high-fat diet-fed mice. The strains were selected based on their fat and glucose absorption inhibitory activities and potential metabolic interactions. The optimal ratio of the two strains in the probiotic formulation was determined based on their adipocyte differentiation inhibitory activities. Treatment of formulations with BEPC22 and BELP53 for 10 weeks decreased body weight gain at 6 weeks; it also decreased the food efficiency ratio, white adipose tissue volume, and adipocyte size. Moreover, it decreased the expression of the lipogenic gene Ppar-γ in the liver, while significantly increasing the expression of the fat oxidation gene Ppar-α in the white adipose tissue. Notably, treatment with a combination of the two strains significantly reduced the plasma levels of the obesity hormone leptin and altered the microbiota and metabolome. The omics data also indicated the alteration of anti-obesity microbes and metabolites such as Akkermansia and indolelactic acid, respectively. These findings suggest that treatment with a combination of BEPC22 and BELP53 exerts synergistic beneficial effects against obesity.
Collapse
Affiliation(s)
- Na-Rae Lee
- Research Institute for Bioactive-Metabolome Network, Konkuk University, Seoul 05029, Republic of Korea
| | - Tae-Jun Kwon
- Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI Hub), Daegu 41061, Republic of Korea.
| | - Eui-Chun Chung
- R&D Center, Hecto Healthcare Co., Ltd, Seoul 06142, Republic of Korea.
| | - Jaewoong Bae
- R&D Center, Hecto Healthcare Co., Ltd, Seoul 06142, Republic of Korea.
| | - Song-Hui Soung
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 05209, Republic of Korea
| | - Hyun-Ji Tak
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 05209, Republic of Korea
| | - Jun-Young Choi
- Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI Hub), Daegu 41061, Republic of Korea.
| | - Young-Eun Lee
- Cognitive Science Research Group, Korea Brain Research Institute, Daegu 41062, Republic of Korea
| | - Nak Won Hwang
- R&D Center, Hecto Healthcare Co., Ltd, Seoul 06142, Republic of Korea.
| | - Jong Seo Lee
- R&D Center, Hecto Healthcare Co., Ltd, Seoul 06142, Republic of Korea.
| | - Kum-Joo Shin
- R&D Center, Hecto Healthcare Co., Ltd, Seoul 06142, Republic of Korea.
| | - Choong Hwan Lee
- Research Institute for Bioactive-Metabolome Network, Konkuk University, Seoul 05029, Republic of Korea
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 05209, Republic of Korea
| | - KilSoo Kim
- Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI Hub), Daegu 41061, Republic of Korea.
- College of Veterinary Medicine, Kyungpook National University, 80 Daehakro, Buk-gu, Daegu 41566, Korea
| | - Seokjin Kim
- R&D Center, Hecto Healthcare Co., Ltd, Seoul 06142, Republic of Korea.
| |
Collapse
|
|
6
|
Li Y, Hu W, Lin B, Ma T, Zhang Z, Hu W, Zhou R, Kwok LY, Sun Z, Zhu C, Zhang H. Omic characterizing and targeting gut dysbiosis in children with autism spectrum disorder: symptom alleviation through combined probiotic and medium-carbohydrate diet intervention - a pilot study. Gut Microbes 2024; 16:2434675. [PMID: 39632378 PMCID: PMC11622613 DOI: 10.1080/19490976.2024.2434675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 10/22/2024] [Accepted: 11/11/2024] [Indexed: 12/07/2024] Open
Abstract
Autism spectrum disorder (ASD) currently lacks effective diagnostic and therapeutic approaches. Disruptions in the gut ecosystem have been observed in individuals with ASD, suggesting that targeting gut microbiota through probiotic and dietary supplementation may serve as a potential treatment strategy. This two-phase study aimed to characterize the fecal metagenome of children with ASD and investigate the beneficial effects of a combined probiotic and medium-carbohydrate intervention in ASD. Fecal metagenomes of children with ASD were compared to those of typically developing children, revealing intestinal dysbiosis in ASD, characterized by reduced levels of Prevotella sp. Dialister invisus, and Bacteroides sp. along with increased predicted abundances of inosine, glutamate, xanthine, and methylxanthine. The gut bacteriome and phageome exhibited high cooperativity. In a 3-month pilot study, Bifidobacterium animalis subsp. lactis Probio-M8 (Probio-M8) was administered alongside a medium-carbohydrate diet to Chinese children with ASD. The primary endpoint was the Childhood Autism Rating Scale (CARS), while the secondary endpoint was the Gastrointestinal Symptom Rating Scale (GSRS). A total of 72 autistic children were initially recruited for the intervention study, but only 53 completed the intervention. Probio-M8, in combination with dietary intervention, significantly improved CARS and GSRS scores, increased fecal levels of Bifidobacterium animalis, Akkermansia muciniphila, Fusicatenibacter saccharivorans, and Sutterella sp. while also reducing Blautia obeum (Benjamini-Hochberg corrected p ≤ 0.05 for all cases). The intervention also modulated fecal metabolites associated with the metabolism of amino acids (lysine), neurotransmitters (glutamate, γ-aminobutyric acid), polyunsaturated fatty acids (arachidonate, myristic acid), and vitamin B3. In conclusion, Probio-M8 combined with medium-carbohydrate diet effectively improved ASD symptoms, with associated changes in the gut microbiome and metabolome, supporting its potential as an adjunctive therapy for ASD.
Collapse
Affiliation(s)
- Yalin Li
- Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
- Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
| | - Weiwei Hu
- Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
- Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
| | - Bing Lin
- Department of Clinical Nutrition Shenzhen Hospital, Southern Medical University, Guangdong, China
- Shenzhen Key Laboratory of Gastrointestinal Microbiota and Disease, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, China
| | - Teng Ma
- Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
- Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
| | - Zhentian Zhang
- Department of Clinical Nutrition Shenzhen Hospital, Southern Medical University, Guangdong, China
- Shenzhen Key Laboratory of Gastrointestinal Microbiota and Disease, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, China
| | - Weiqian Hu
- Department of Clinical Nutrition Shenzhen Hospital, Southern Medical University, Guangdong, China
- Shenzhen Key Laboratory of Gastrointestinal Microbiota and Disease, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, China
| | - Rui Zhou
- Department of Clinical Nutrition Shenzhen Hospital, Southern Medical University, Guangdong, China
- Shenzhen Key Laboratory of Gastrointestinal Microbiota and Disease, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, China
| | - Lai-Yu Kwok
- Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
- Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
| | - Zhihong Sun
- Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
- Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
| | - Cuifeng Zhu
- Department of Clinical Nutrition Shenzhen Hospital, Southern Medical University, Guangdong, China
- Shenzhen Key Laboratory of Gastrointestinal Microbiota and Disease, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, China
| | - Heping Zhang
- Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
- Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China
| |
Collapse
|
|
7
|
Yong GJM, Porsche CE, Sitarik AR, Fujimura KE, McCauley K, Nguyen DT, Levin AM, Woodcroft KJ, Ownby DR, Rundle AG, Johnson CC, Cassidy-Bushrow A, Lynch SV. Precocious infant fecal microbiome promotes enterocyte barrier dysfuction, altered neuroendocrine signaling and associates with increased childhood obesity risk. Gut Microbes 2024; 16:2290661. [PMID: 38117587 PMCID: PMC10761186 DOI: 10.1080/19490976.2023.2290661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 11/29/2023] [Indexed: 12/22/2023] Open
Abstract
Early life gut microbiome composition has been correlated with childhood obesity, though microbial functional contributions to disease origins remain unclear. Here, using an infant birth cohort (n = 349) we identify a distinct fecal microbiota composition in 1-month-old infants with the lowest rate of exclusive breastfeeding, that relates with higher relative risk for obesity and overweight phenotypes at two years. Higher-risk infant fecal microbiomes exhibited accelerated taxonomic and functional maturation and broad-ranging metabolic reprogramming, including reduced concentrations of neuro-endocrine signals. In vitro, exposure of enterocytes to fecal extracts from higher-risk infants led to upregulation of genes associated with obesity and with expansion of nutrient sensing enteroendocrine progenitor cells. Fecal extracts from higher-risk infants also promoted enterocyte barrier dysfunction. These data implicate dysregulation of infant microbiome functional development, and more specifically promotion of enteroendocrine signaling and epithelial barrier impairment in the early-life developmental origins of childhood obesity.
Collapse
Affiliation(s)
- Germaine J. M. Yong
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
- Asian Microbiome Library Pte Ltd, Singapore and Singapore Institute of Food and Biotechnology Innovation, Singapore, Singapore
| | - Cara E. Porsche
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
| | - Alexandra R. Sitarik
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | - Kei E. Fujimura
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
- Genetic Disease Laboratory, California Department of Public Health, San Francisco, CA, USA
| | - Kathryn McCauley
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
| | - Dat T. Nguyen
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
- Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Albert M. Levin
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | | | - Dennis R. Ownby
- Division of Allergy and Clinical Immunology, Department of Pediatrics, Augusta University, Augusta, GA, USA
| | - Andrew G. Rundle
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Christine C. Johnson
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | | | - Susan V. Lynch
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
| |
Collapse
|
|
8
|
Hu JY, Lv M, Zhang KL, Qiao XY, Wang YX, Wang FY. Evaluating the causal relationship between human blood metabolites and gastroesophageal reflux disease. World J Gastrointest Oncol 2023; 15:2169-2184. [PMID: 38173433 PMCID: PMC10758654 DOI: 10.4251/wjgo.v15.i12.2169] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 10/01/2023] [Accepted: 10/30/2023] [Indexed: 12/14/2023] Open
Abstract
BACKGROUND Gastroesophageal reflux disease (GERD) affects approximately 13% of the global population. However, the pathogenesis of GERD has not been fully elucidated. The development of metabolomics as a branch of systems biology in recent years has opened up new avenues for the investigation of disease processes. As a powerful statistical tool, Mendelian randomization (MR) is widely used to explore the causal relationship between exposure and outcome. AIM To analyze of the relationship between 486 blood metabolites and GERD. METHODS Two-sample MR analysis was used to assess the causal relationship between blood metabolites and GERD. A genome-wide association study (GWAS) of 486 metabolites was the exposure, and two different GWAS datasets of GERD were used as endpoints for the base analysis and replication and meta-analysis. Bonferroni correction is used to determine causal correlation features (P < 1.03 × 10-4). The results were subjected to sensitivity analysis to assess heterogeneity and pleiotropy. Using the MR Steiger filtration method to detect whether there is a reverse causal relationship between metabolites and GERD. In addition, metabolic pathway analysis was conducted using the online database based MetaboAnalyst 5.0 software. RESULTS In MR analysis, four blood metabolites are negatively correlated with GERD: Levulinate (4-oxovalerate), stearate (18:0), adrenate (22:4n6) and p-acetamidophenylglucuronide. However, we also found a positive correlation between four blood metabolites and GERD: Kynurenine, 1-linoleoylglycerophosphoethanolamine, butyrylcarnitine and guanosine. And bonferroni correction showed that butyrylcarnitine (odd ratio 1.10, 95% confidence interval: 1.05-1.16, P = 7.71 × 10-5) was the most reliable causal metabolite. In addition, one significant pathways, the "glycerophospholipid metabolism" pathway, can be involved in the pathogenesis of GERD. CONCLUSION Our study found through the integration of genomics and metabolomics that butyrylcarnitine may be a potential biomarker for GERD, which will help further elucidate the pathogenesis of GERD and better guide its treatment. At the same time, this also contributes to early screening and prevention of GERD. However, the results of this study require further confirmation from both basic and clinical real-world studies.
Collapse
Affiliation(s)
- Jia-Yan Hu
- Institute of Digestive Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Mi Lv
- Institute of Digestive Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Kun-Li Zhang
- Institute of Digestive Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Xi-Yun Qiao
- Institute of Digestive Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Yu-Xi Wang
- Institute of Digestive Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Feng-Yun Wang
- Institute of Digestive Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| |
Collapse
|
|
9
|
Tsukagoshi-Yamaguchi A, Koshizaka M, Ishibashi R, Ishikawa K, Ishikawa T, Shoji M, Ide S, Ide K, Baba Y, Terayama R, Hattori A, Takemoto M, Ouchi Y, Maezawa Y, Yokote K. Metabolomic analysis of serum samples from a clinical study on ipragliflozin and metformin treatment in Japanese patients with type 2 diabetes: Exploring human metabolites associated with visceral fat reduction. Pharmacotherapy 2023; 43:1317-1326. [PMID: 37772313 DOI: 10.1002/phar.2884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 09/02/2023] [Accepted: 09/05/2023] [Indexed: 09/30/2023]
Abstract
STUDY OBJECTIVE The effects of the sodium-dependent glucose transporter-2 inhibitor ipragliflozin were compared with metformin in a previous study, which revealed that ipragliflozin reduced visceral fat content by 12%; however, the underlying mechanism was unclear. Therefore, this sub-analysis aimed to compare metabolomic changes associated with ipragliflozin and metformin that may contribute to their biological effects. DESIGN A sub-analysis of a randomized controlled study. SETTING Chiba University Hospital and ten hospitals in Japan. PATIENTS Fifteen patients with type 2 diabetes in the ipragliflozin group and 15 patients with type 2 diabetes in the metformin group with matching characteristics, such as age, sex, baseline A1C, baseline visceral fat area, smoking status, and concomitant medication. INTERVENTIONS Ipragliflozin 50 mg or metformin 1000 mg daily. MEASUREMENTS The clinical data were reanalyzed, and metabolomic analysis of serum samples collected before and 24 weeks after drug administration was performed using capillary electrophoresis time-of-flight mass spectrometry. MAIN RESULTS The reduction in the mean visceral fat area after 24 weeks of treatment was significantly larger (p = 0.002) in the ipragliflozin group (-19.8%) than in the metformin group (-2.5%), as were the subcutaneous fat area and body weight. The A1C and blood glucose levels decreased in both groups. Glutamic pyruvic oxaloacetic transaminase, γ-glutamyl transferase, uric acid, and triglyceride levels decreased in the ipragliflozin group. Low-density lipoprotein cholesterol levels decreased in the metformin group. After ipragliflozin administration, N2-phenylacetylglutamine, inosine, guanosine, and 1-methyladenosine levels increased, whereas galactosamine, glucosamine, 11-aminoundecanoic acid, morpholine, and choline levels decreased. After metformin administration, metformin, hypotaurine, methionine, methyl-2-oxovaleric acid, 3-nitrotyrosine, and cyclohexylamine levels increased, whereas citrulline, octanoic acid, indole-3-acetaldehyde, and hexanoic acid levels decreased. CONCLUSIONS Metabolites that may affect visceral fat reduction were detected in the ipragliflozin group. Studies are required to further elucidate the underlying mechanisms.
Collapse
Affiliation(s)
| | - Masaya Koshizaka
- Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan
- Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan
- Center for Preventive Medical Science, Chiba University, Chiba City, Japan
| | - Ryoichi Ishibashi
- Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan
- Division of Diabetes, Endocrinology, and Metabolism, Kimitsu Chuo Hospital, Kisarazu City, Japan
| | - Ko Ishikawa
- Department of Diabetes and Endocrinology, Chiba Rosai Hospital, Ichihara City, Japan
| | - Takahiro Ishikawa
- Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan
- Department of General Medical Science, Chiba University Graduate School of Medicine, Chiba City, Japan
| | - Mayumi Shoji
- Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan
- Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan
| | - Shintaro Ide
- Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan
- Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan
| | - Kana Ide
- Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan
- Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan
| | - Yusuke Baba
- Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan
- Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan
| | - Ryo Terayama
- Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan
| | - Akiko Hattori
- Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan
- Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan
| | - Minoru Takemoto
- Division of Diabetes, Department of Medicine, Metabolism and Endocrinology, International University of Health and Welfare, Narita City, Japan
| | - Yasuo Ouchi
- Department of Regenerative Medicine, Chiba University Graduate School of Medicine, Chiba City, Japan
- Altos Labs, California, San Diego, USA
| | - Yoshiro Maezawa
- Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan
- Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan
| | - Koutaro Yokote
- Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba City, Japan
- Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba City, Japan
| |
Collapse
|
|
10
|
Qi L, Ye Z, Lin H. Identification of Differential Metabolites Between
Type 2 Diabetes and Postchronic Pancreatitis Diabetes (Type 3c) Based on an Untargeted Metabolomics Approach. Lab Med 2023; 54:562-573. [PMID: 36864551 DOI: 10.1093/labmed/lmad004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/04/2023] Open
Abstract
OBJECTIVE A nontargeted metabolomics approach was established to characterize serum metabolic profile in type 3c diabetes mellitus (T3cDM) secondary to chronic pancreatitis and compare with T2DM. METHODS Forty patients were recruited for metabolite analysis based on liquid chromatography-mass spectrometry. Cluster heatmap and KEGG metabolic pathway enrichment analysis were used to analyze the specific and differential metabolites. The receiver operating characteristics (ROCs) were generated and correlation analysis with clinical data was conducted. RESULTS Metabolites including sphingosine, lipids, carnitine, bile acid, and hippuric acid were found to be different between T2DM and T3cDM, mainly enriched in bile acid biosynthesis, fatty acid biosynthesis, and sphingolipid metabolic pathways. The ROCs were generated with an area under the curve of 0.907 (95% confidence interval, 0.726-1) for the model with 15 metabolites. CONCLUSION T3cDM is characterized by increased sphingosine, carnitine, bile acid, and most lipids, providing novel biomarkers for clinical diagnosis and a future direction in research on pathophysiological mechanisms.
Collapse
Affiliation(s)
- Liang Qi
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Zheng Ye
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China
| | - Hao Lin
- Department of Clinical Science and Research, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| |
Collapse
|
|
11
|
Witkowska AM, Salem JE. Pharmacological and Nutritional Modulation of Metabolome and Metagenome in Cardiometabolic Disorders. Biomolecules 2023; 13:1340. [PMID: 37759740 PMCID: PMC10526920 DOI: 10.3390/biom13091340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 08/30/2023] [Accepted: 08/31/2023] [Indexed: 09/29/2023] Open
Abstract
Cardiometabolic disorders are major causes of morbidity and mortality worldwide. A growing body of research indicates that the gut microbiota, whether it interacts favorably or not, plays an important role in host metabolism. Elucidating metabolic pathways may be crucial in preventing and treating cardiometabolic diseases, and omics methods are key to studying the interaction between the fecal microbiota and host metabolism. This review summarizes available studies that combine metabolomic and metagenomic approaches to describe the effects of drugs, diet, nutrients, and specific foods on cardiometabolic health and to identify potential targets for future research.
Collapse
Affiliation(s)
- Anna Maria Witkowska
- Department of Food Biotechnology, Faculty of Health Sciences, Medical University of Bialystok, Szpitalna 37, 15-295 Białystok, Poland
| | - Joe-Elie Salem
- Department of Pharmacology, Pitié-Salpêtrière Hospital, Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical Investigation Center (CIC-1901), Assistance Publique-Hôpitaux de Paris (AP-HP), Sorbonne Université, 75013 Paris, France;
| |
Collapse
|
|
12
|
Tilves C, Tanaka T, Differding MK, Spira AP, Chia CW, Ferrucci L, Mueller NT. The gut microbiome and regional fat distribution: Findings from the Baltimore Longitudinal Study of Aging. Obesity (Silver Spring) 2023; 31:1425-1435. [PMID: 37016727 PMCID: PMC10191998 DOI: 10.1002/oby.23717] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 12/11/2022] [Accepted: 12/26/2022] [Indexed: 04/06/2023]
Abstract
OBJECTIVE The aim of this study was to examine associations of gut microbiome diversity and composition with directly measured regional fat distribution, including central fat, in a large community-based cohort. METHODS A cross-sectional investigation was conducted in the Baltimore Longitudinal Study of Aging (N = 815, 55.2% female, 65.9% White). The fecal microbiome was assessed using whole-genome shotgun metagenomic sequencing, and trunk and leg fat was measured using dual x-ray absorptiometry. Multivariable-adjusted associations of regional fat measures, BMI, or waist circumference with microbiome alpha diversity metrics, microbiome beta diversity metrics, and species differential abundance (verified using two compositional statistical approaches) were examined. RESULTS Trunk fat, leg fat, BMI, and waist circumference all significantly explained similar amounts of variance in microbiome structure. Differential abundance testing identified 11 bacterial species significantly associated with at least one measure of body composition or anthropometry. Ruminococcus gnavus was strongly and consistently associated with trunk fat mass, which is congruent with prior literature. CONCLUSIONS Microbiome diversity and composition, in particular higher abundance of Ruminococcus gnavus, were associated with greater trunk fat, in addition to other measures of obesity. Longitudinal studies are needed to replicate these findings, and if replicated, randomized trials are needed to determine whether interventions targeting microbiome features such as abundance of Ruminococcus gnavus can lead to reductions in trunk fat and its metabolic sequelae.
Collapse
Affiliation(s)
- Curtis Tilves
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
- Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
| | - Toshiko Tanaka
- Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
| | - Moira K. Differding
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
- Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
| | - Adam P. Spira
- Department of Mental Health, Johns Hopkins Bloomberg School of Public Health
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine
- Center on Aging and Health, Johns Hopkins University
| | - Chee W. Chia
- Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
| | - Luigi Ferrucci
- Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
| | - Noel T. Mueller
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
- Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
| |
Collapse
|
|
13
|
Vitek L, Hinds TD, Stec DE, Tiribelli C. The physiology of bilirubin: health and disease equilibrium. Trends Mol Med 2023; 29:315-328. [PMID: 36828710 PMCID: PMC10023336 DOI: 10.1016/j.molmed.2023.01.007] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 01/25/2023] [Accepted: 01/27/2023] [Indexed: 02/24/2023]
Abstract
Bilirubin has several physiological functions, both beneficial and harmful. In addition to reactive oxygen species-scavenging activities, bilirubin has potent immunosuppressive effects associated with long-term pathophysiological sequelae. It has been recently recognized as a hormone with endocrine actions and interconnected effects on various cellular signaling pathways. Current studies show that bilirubin also decreases adiposity and prevents metabolic and cardiovascular diseases. All in all, the physiological importance of bilirubin is only now coming to light, and strategies for increasing plasma bilirubin levels to combat chronic diseases are starting to be considered. This review discusses the beneficial effects of increasing plasma bilirubin, incorporates emerging areas of bilirubin biology, and provides key concepts to advance the field.
Collapse
Affiliation(s)
- Libor Vitek
- Fourth Department of Internal Medicine and Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 120 00 Prague, Czech Republic
| | - Terry D Hinds
- Department of Pharmacology and Nutritional Sciences, Barnstable Brown Diabetes Center, Markey Cancer Center, University of Kentucky, Lexington, KY 40508, USA
| | - David E Stec
- Department of Physiology and Biophysics, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA
| | | |
Collapse
|
|
14
|
Noerman S, Landberg R. Blood metabolite profiles linking dietary patterns with health-Toward precision nutrition. J Intern Med 2023; 293:408-432. [PMID: 36484466 DOI: 10.1111/joim.13596] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Diet is one of the most important exposures that may affect health throughout life span. Investigations on dietary patterns rather than single food components are gaining in popularity because they take the complexity of the whole dietary context into account. Adherence to such dietary patterns can be measured by using metabolomics, which allows measurements of thousands of molecules simultaneously. Derived metabolite signatures of dietary patterns may reflect the consumption of specific groups of foods or their constituents originating from the dietary pattern per se, or the physiological response toward the food-derived metabolites, their interaction with endogenous metabolism, and exogenous factors such as gut microbiota. Here, we review and discuss blood metabolite fingerprints of healthy dietary patterns. The plasma concentration of several food-derived metabolites-such as betaines from whole grains and n - 3 polyunsaturated fatty acids and furan fatty acids from fish-seems to consistently reflect the intake of common foods of several healthy dietary patterns. The metabolites reflecting shared features of different healthy food indices form biomarker panels for which specific, targeted assays could be developed. The specificity of such biomarker panels would need to be validated, and proof-of-concept feeding trials are needed to evaluate to what extent the panels may mediate the effects of dietary patterns on disease risk indicators or if they are merely food intake biomarkers. Metabolites mediating health effects may represent novel targets for precision prevention strategies of clinical relevance to be verified in future studies.
Collapse
Affiliation(s)
- Stefania Noerman
- Department of Biology and Biological Engineering, Division of Food and Nutrition Science, Chalmers University of Technology, Gothenburg, Sweden
| | - Rikard Landberg
- Department of Biology and Biological Engineering, Division of Food and Nutrition Science, Chalmers University of Technology, Gothenburg, Sweden
| |
Collapse
|
|
15
|
Newman TM, Clear KYJ, Wilson AS, Soto-Pantoja DR, Ochs-Balcom HM, Cook KL. Early-life dietary exposures mediate persistent shifts in the gut microbiome and visceral fat metabolism. Am J Physiol Cell Physiol 2023; 324:C644-C657. [PMID: 35848617 PMCID: PMC9970661 DOI: 10.1152/ajpcell.00380.2021] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
In utero dietary exposures are linked to the development of metabolic syndrome in adult offspring. These dietary exposures can potentially impact gut microbial composition and offspring metabolic health. Female BALB/c mice were administered a lard, lard + flaxseed oil, high sugar, or control diet 4 wk before mating, throughout mating, pregnancy, and lactation. Female offspring were offered low-fat control diet at weaning. Fecal 16S sequencing was performed. Untargeted metabolomics was performed on visceral adipose tissue (VAT) of adult female offspring. Immunohistochemistry was used to determine adipocyte size, VAT collagen deposition, and macrophage content. Hippurate was administered via weekly intraperitoneal injections to low-fat and high-fat diet-fed female mice and VAT fibrosis and collagen 1A (COL1A) were assessed by immunohistochemistry. Lard diet exposure was associated with elevated body and VAT weight and dysregulated glucose metabolism. Lard + flaxseed oil attenuated these effects. Lard diet exposures were associated with increased adipocyte diameter and VAT macrophage count. Lard + flaxseed oil reduced adipocyte diameter and fibrosis compared with the lard diet. Hippurate-associated bacteria were influenced by lard versus lard + flax exposures that persisted to adulthood. VAT hippurate was increased in lard + flaxseed oil compared with lard diet. Hippurate supplementation mitigated VAT fibrosis pathology. Maternal high-fat lard diet consumption resulted in long-term metabolic and gut microbiome programming in offspring, impacting VAT inflammation and fibrosis, and was associated with reduced VAT hippurate content. These traits were not observed in maternal high-fat lard + flaxseed oil diet-exposed offspring. Hippurate supplementation reduced VAT fibrosis. These data suggest that detrimental effects of early-life high-fat lard diet exposure can be attenuated by dietary omega-3 polyunsaturated fatty acid supplementation.
Collapse
Affiliation(s)
- Tiffany M. Newman
- 1Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina,2Department of Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Kenysha Y. J. Clear
- 2Department of Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Adam S. Wilson
- 2Department of Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - David R. Soto-Pantoja
- 1Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina,2Department of Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina,3Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Heather M. Ochs-Balcom
- 4Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York
| | - Katherine L. Cook
- 1Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina,2Department of Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina,3Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, North Carolina
| |
Collapse
|
|
16
|
Disentangling the Complexity of Nutrition, Frailty and Gut Microbial Pathways during Aging: A Focus on Hippuric Acid. Nutrients 2023; 15:nu15051138. [PMID: 36904138 PMCID: PMC10005077 DOI: 10.3390/nu15051138] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 02/16/2023] [Accepted: 02/23/2023] [Indexed: 02/26/2023] Open
Abstract
Hippuric acid (HA) is a metabolite resulting from the hepatic glycine conjugation of benzoic acid (BA) or from the gut bacterial metabolism of phenylalanine. BA is generally produced by gut microbial metabolic pathways after the ingestion of foods of vegetal origin rich in polyphenolic compounds, namely, chlorogenic acids or epicatechins. It can also be present in foods, either naturally or artificially added as a preservative. The plasma and urine HA levels have been used in nutritional research for estimating the habitual fruit and vegetable intake, especially in children and in patients with metabolic diseases. HA has also been proposed as a biomarker of aging, since its levels in the plasma and urine can be influenced by the presence of several age-related conditions, including frailty, sarcopenia and cognitive impairment. Subjects with physical frailty generally exhibit reduced plasma and urine levels of HA, despite the fact that HA excretion tends to increase with aging. Conversely, subjects with chronic kidney disease exhibit reduced HA clearance, with HA retention that may exert toxic effects on the circulation, brain and kidneys. With regard to older patients with frailty and multimorbidity, interpreting the HA levels in the plasma and urine may result particularly challenging because HA is at the crossroads between diet, gut microbiota, liver and kidney function. Although these considerations may not make HA the ideal biomarker of aging trajectories, the study of its metabolism and clearance in older subjects may provide valuable information for disentangling the complex interaction between diet, gut microbiota, frailty and multimorbidity.
Collapse
|
|
17
|
Shah RV, Steffen LM, Nayor M, Reis JP, Jacobs DR, Allen NB, Lloyd-Jones D, Meyer K, Cole J, Piaggi P, Vasan RS, Clish CB, Murthy VL. Dietary metabolic signatures and cardiometabolic risk. Eur Heart J 2023; 44:557-569. [PMID: 36424694 PMCID: PMC10169425 DOI: 10.1093/eurheartj/ehac446] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 06/23/2022] [Accepted: 07/28/2022] [Indexed: 11/27/2022] Open
Abstract
AIMS Observational studies of diet in cardiometabolic-cardiovascular disease (CM-CVD) focus on self-reported consumption of food or dietary pattern, with limited information on individual metabolic responses to dietary intake linked to CM-CVD. Here, machine learning approaches were used to identify individual metabolic patterns related to diet and relation to long-term CM-CVD in early adulthood. METHODS AND RESULTS In 2259 White and Black adults (age 32.1 ± 3.6 years, 45% women, 44% Black) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, multivariate models were employed to identify metabolite signatures of food group and composite dietary intake across 17 food groups, 2 nutrient groups, and healthy eating index-2015 (HEI2015) diet quality score. A broad array of metabolites associated with diet were uncovered, reflecting food-related components/catabolites (e.g. fish and long-chain unsaturated triacylglycerols), interactions with host features (microbiome), or pathways broadly implicated in CM-CVD (e.g. ceramide/sphingomyelin lipid metabolism). To integrate diet with metabolism, penalized machine learning models were used to define a metabolite signature linked to a putative CM-CVD-adverse diet (e.g. high in red/processed meat, refined grains), which was subsequently associated with long-term diabetes and CVD risk numerically more strongly than HEI2015 in CARDIA [e.g. diabetes: standardized hazard ratio (HR): 1.62, 95% confidence interval (CI): 1.32-1.97, P < 0.0001; CVD: HR: 1.55, 95% CI: 1.12-2.14, P = 0.008], with associations replicated for diabetes (P < 0.0001) in the Framingham Heart Study. CONCLUSION Metabolic signatures of diet are associated with long-term CM-CVD independent of lifestyle and traditional risk factors. Metabolomics improves precision to identify adverse consequences and pathways of diet-related CM-CVD.
Collapse
Affiliation(s)
- Ravi V Shah
- Vanderbilt University Medical Center, Vanderbilt Clinical and Translational Research Center (VTRACC), Nashville, TN, USA
| | - Lyn M Steffen
- Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA
| | - Matthew Nayor
- Cardiology Division, Boston University School of Medicine, Boston, MA, USA
| | - Jared P Reis
- Epidemiology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA
| | - David R Jacobs
- Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA
| | - Norrina B Allen
- Department of Preventive Medicine, Northwestern University, Chicago, IL, USA
| | - Donald Lloyd-Jones
- Department of Preventive Medicine, Northwestern University, Chicago, IL, USA
| | - Katie Meyer
- Nutrition Department, UNC Chapel Hill, Chapel Hill, NC, USA
| | - Joanne Cole
- Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Paolo Piaggi
- Department of Information Engineering, University of Pisa, Pisa, Italy
| | - Ramachandran S Vasan
- Sections of Preventive Medicine and Epidemiology and Cardiovascular Medicine, Department of Medicine, and Department of Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA, USA
- The Framingham Heart Study, Framingham, MA, USA
| | - Clary B Clish
- Broad Institute of Harvard and MIT, Cambridge, MA, USA
| | - Venkatesh L Murthy
- Department of Medicine and Radiology, University of Michigan, 1338 Cardiovascular Center, Ann Arbor, MI 48109-5873, USA
| |
Collapse
|
|
18
|
Vecchiato CG, Golinelli S, Pinna C, Pilla R, Suchodolski JS, Tvarijonaviciute A, Rubio CP, Dorato E, Delsante C, Stefanelli C, Pagani E, Fracassi F, Biagi G. Fecal microbiota and inflammatory and antioxidant status of obese and lean dogs, and the effect of caloric restriction. Front Microbiol 2023; 13:1050474. [PMID: 36713218 PMCID: PMC9878458 DOI: 10.3389/fmicb.2022.1050474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 12/19/2022] [Indexed: 01/15/2023] Open
Abstract
Introduction Obesity is the most common nutritional disease in dogs, and is generally managed by caloric restriction. Gut microbiota alteration could represent a predisposing factor for obesity development, which has been associated with a low-grade inflammatory condition and an impaired antioxidant status. Besides, weight loss has been shown to influence the gut microbiota composition and reduce the inflammatory response and oxidative stress. Method However, these insights in canine obesity have not been fully elucidated. The aim of this study was to assess the differences in serum and inflammatory parameters, antioxidant status, fecal microbiota and bacterial metabolites in 16 obese and 15 lean client-owned dogs and how these parameters in obese may be influenced by caloric restriction. First, for 30 days, all dogs received a high-protein, high-fiber diet in amounts to maintain their body weight; later, obese dogs were fed for 180 days the same diet in restricted amounts to promote weight loss. Results Before the introduction of the experimental diet (T0), small differences in fecal microbial populations were detected between obese and lean dogs, but bacterial diversity and main bacterial metabolites did not differ. The fecal Dysbiosis Index (DI) was within the reference range (< 0) in most of dogs of both groups. Compared to lean dogs, obese dogs showed higher serum concentrations of acute-phase proteins, total thyroxine (TT4), and antioxidant capacity. Compared to T0, dietary treatment affected the fecal microbiota of obese dogs, decreasing the abundance of Firmicutes and increasing Bacteroides spp. However, these changes did not significantly affect the DI. The caloric restriction failed to exert significative changes on a large scale on bacterial populations. Consequently, the DI, bacterial diversity indices and metabolites were unaffected in obese dogs. Caloric restriction was not associated with a reduction of inflammatory markers or an improvement of the antioxidant status, while an increase of TT4 has been observed. Discussion In summary, the present results underline that canine obesity is associated with chronic inflammation. This study highlights that changes on fecal microbiota of obese dogs induced by the characteristics of the diet should be differentiated from those that are the consequence of the reduced energy intake.
Collapse
Affiliation(s)
- Carla Giuditta Vecchiato
- Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy,*Correspondence: Carla Giuditta Vecchiato, ✉
| | - Stefania Golinelli
- Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy
| | - Carlo Pinna
- Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy
| | - Rachel Pilla
- Gastrointestinal Laboratory, Texas A&M University, College Station, TX, United States
| | - Jan S. Suchodolski
- Gastrointestinal Laboratory, Texas A&M University, College Station, TX, United States
| | - Asta Tvarijonaviciute
- Interdisciplinary Laboratory of Clinical Analysis, Interlab-UMU, Regional Campus of International Excellence 'Campus Mare Nostrum', University of Murcia, Murcia, Spain
| | - Camila Peres Rubio
- Department of Animal and Food Science, School of Veterinary Science, Autonomous University of Barcelona, Barcelona, Spain
| | - Elisa Dorato
- Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy
| | - Costanza Delsante
- Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy
| | - Claudio Stefanelli
- Dipartimento di Scienze per la Qualità della Vita, University of Bologna, Rimini, Italy
| | - Elena Pagani
- Monge & C. S.p.A., Monasterolo di Savigliano, Italy
| | - Federico Fracassi
- Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy
| | - Giacomo Biagi
- Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy
| |
Collapse
|
|
19
|
Zhang L, Zheng J, Ismond KP, MacKay S, LeVatte M, Constable J, Alatise OI, Kingham TP, Wishart DS. Identification of urinary biomarkers of colorectal cancer: Towards the development of a colorectal screening test in limited resource settings. Cancer Biomark 2023; 36:17-30. [PMID: 35871322 PMCID: PMC10627333 DOI: 10.3233/cbm-220034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
BACKGROUND African colorectal cancer (CRC) rates are rising rapidly. A low-cost CRC screening approach is needed to identify CRC from non-CRC patients who should be sent for colonoscopy (a scarcity in Africa). OBJECTIVE To identify urinary metabolite biomarkers that, combined with easy-to-measure clinical variables, would identify patients that should be further screened for CRC by colonoscopy. Ideal metabolites would be water-soluble and easily translated into a sensitive, low-cost point-of-care (POC) test. METHODS Liquid-chromatography mass spectrometry (LC-MS/MS) was used to quantify 142 metabolites in spot urine samples from 514 Nigerian CRC patients and healthy controls. Metabolite concentration data and clinical characteristics were used to determine optimal sets of biomarkers for identifying CRC from non-CRC subjects. RESULTS Our statistical analysis identified N1, N12-diacetylspermine, hippurate, p-hydroxyhippurate, and glutamate as the best metabolites to discriminate CRC patients via POC screening. Logistic regression modeling using these metabolites plus clinical data achieved an area under the receiver-operator characteristic (AUCs) curves of 89.2% for the discovery set, and 89.7% for a separate validation set. CONCLUSIONS Effective urinary biomarkers for CRC screening do exist. These results could be transferred into a simple, POC urinary test for screening CRC patients in Africa.
Collapse
Affiliation(s)
- Lun Zhang
- Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
| | - Jiamin Zheng
- Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
| | | | - Scott MacKay
- Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
| | - Marcia LeVatte
- Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
| | - Jeremy Constable
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Olusegun Isaac Alatise
- Department of Surgery, Obafemi Awolowo University and Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria
| | - T. Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - David S. Wishart
- Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
- Department of Computing Science, University of Alberta, Edmonton, AB, Canada
| |
Collapse
|
|
20
|
Bacorn M, Romero-Soto HN, Levy S, Chen Q, Hourigan SK. The Gut Microbiome of Children during the COVID-19 Pandemic. Microorganisms 2022; 10:microorganisms10122460. [PMID: 36557713 PMCID: PMC9783902 DOI: 10.3390/microorganisms10122460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 12/07/2022] [Accepted: 12/09/2022] [Indexed: 12/15/2022] Open
Abstract
The gut microbiome has been shown to play a critical role in maintaining a healthy state. Dysbiosis of the gut microbiome is involved in modulating disease severity and potentially contributes to long-term outcomes in adults with COVID-19. Due to children having a significantly lower risk of severe illness and limited sample availability, much less is known about the role of the gut microbiome in children with COVID-19. It is well recognized that the developing gut microbiome of children differs from that of adults, but it is unclear if this difference contributes to the different clinical presentations and complications. In this review, we discuss the current knowledge of the gut microbiome in children with COVID-19, with gut microbiome dysbiosis being found in pediatric COVID-19 but specific taxa change often differing from those described in adults. Additionally, we discuss possible mechanisms of how the gut microbiome may mediate the presentation and complications of COVID-19 in children and the potential role for microbial therapeutics.
Collapse
|
|
21
|
Kuznetzova AB, Prazdnova EV, Chistyakov VA, Kutsevalova OY, Batiushin MM. Are Probiotics Needed in Nephrology? NEPHROLOGY (SAINT-PETERSBURG) 2022; 26:18-30. [DOI: 10.36485/1561-6274-2022-26-4-18-30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Affiliation(s)
- A. B. Kuznetzova
- Academy of Biology and Biotechnology named after D.I. Ivanovsky, Southern Federal University
| | - E. V. Prazdnova
- Academy of Biology and Biotechnology named after D.I. Ivanovsky, Southern Federal University
| | - V. A. Chistyakov
- Academy of Biology and Biotechnology named after D.I. Ivanovsky, Southern Federal University
| | - O. Yu. Kutsevalova
- Federal State Budgetary Institution "National Medical Research Center of Oncology"
| | | |
Collapse
|
|
22
|
Zelicha H, Kloting N, Kaplan A, Yaskolka Meir A, Rinott E, Tsaban G, Chassidim Y, Bluher M, Ceglarek U, Isermann B, Stumvoll M, Quayson RN, von Bergen M, Engelmann B, Rolle-Kampczyk UE, Haange SB, Tuohy KM, Diotallevi C, Shelef I, Hu FB, Stampfer MJ, Shai I. The effect of high-polyphenol Mediterranean diet on visceral adiposity: the DIRECT PLUS randomized controlled trial. BMC Med 2022; 20:327. [PMID: 36175997 PMCID: PMC9523931 DOI: 10.1186/s12916-022-02525-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 08/11/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Mediterranean (MED) diet is a rich source of polyphenols, which benefit adiposity by several mechanisms. We explored the effect of the green-MED diet, twice fortified in dietary polyphenols and lower in red/processed meat, on visceral adipose tissue (VAT). METHODS In the 18-month Dietary Intervention Randomized Controlled Trial PoLyphenols UnproceSsed (DIRECT-PLUS) weight-loss trial, 294 participants were randomized to (A) healthy dietary guidelines (HDG), (B) MED, or (C) green-MED diets, all combined with physical activity. Both isocaloric MED groups consumed 28 g/day of walnuts (+ 440 mg/day polyphenols). The green-MED group further consumed green tea (3-4 cups/day) and Wolffia globosa (duckweed strain) plant green shake (100 g frozen cubes/day) (+ 800mg/day polyphenols) and reduced red meat intake. We used magnetic resonance imaging (MRI) to quantify the abdominal adipose tissues. RESULTS Participants (age = 51 years; 88% men; body mass index = 31.2 kg/m2; 29% VAT) had an 89.8% retention rate and 79.3% completed eligible MRIs. While both MED diets reached similar moderate weight (MED: - 2.7%, green-MED: - 3.9%) and waist circumference (MED: - 4.7%, green-MED: - 5.7%) loss, the green-MED dieters doubled the VAT loss (HDG: - 4.2%, MED: - 6.0%, green-MED: - 14.1%; p < 0.05, independent of age, sex, waist circumference, or weight loss). Higher dietary consumption of green tea, walnuts, and Wolffia globosa; lower red meat intake; higher total plasma polyphenols (mainly hippuric acid), and elevated urine urolithin A polyphenol were significantly related to greater VAT loss (p < 0.05, multivariate models). CONCLUSIONS A green-MED diet, enriched with plant-based polyphenols and lower in red/processed meat, may be a potent intervention to promote visceral adiposity regression. TRIAL REGISTRATION ClinicalTrials.gov , NCT03020186.
Collapse
Affiliation(s)
- Hila Zelicha
- Faculty of Health Sciences, The Health & Nutrition Innovative International Research Center, Ben-Gurion University of the Negev, P.O. Box 653, 84105, Be'er Sheva, Israel
| | - Nora Kloting
- Department of Medicine, University of Leipzig, Leipzig, Germany
| | - Alon Kaplan
- Faculty of Health Sciences, The Health & Nutrition Innovative International Research Center, Ben-Gurion University of the Negev, P.O. Box 653, 84105, Be'er Sheva, Israel
| | - Anat Yaskolka Meir
- Faculty of Health Sciences, The Health & Nutrition Innovative International Research Center, Ben-Gurion University of the Negev, P.O. Box 653, 84105, Be'er Sheva, Israel
| | - Ehud Rinott
- Faculty of Health Sciences, The Health & Nutrition Innovative International Research Center, Ben-Gurion University of the Negev, P.O. Box 653, 84105, Be'er Sheva, Israel
| | - Gal Tsaban
- Faculty of Health Sciences, The Health & Nutrition Innovative International Research Center, Ben-Gurion University of the Negev, P.O. Box 653, 84105, Be'er Sheva, Israel
| | - Yoash Chassidim
- Department of Engineering, Sapir Academic College, Ashkelon, Israel
| | - Matthias Bluher
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany
| | - Uta Ceglarek
- Department of Medicine, University of Leipzig, Leipzig, Germany
| | - Berend Isermann
- Department of Medicine, University of Leipzig, Leipzig, Germany
| | | | | | | | | | | | | | - Kieran M Tuohy
- Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach, San Michele all'Adige, Trentino, Italy
| | - Camilla Diotallevi
- Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach, San Michele all'Adige, Trentino, Italy
| | - Ilan Shelef
- Soroka University Medical Center, Be'er Sheva, Israel
| | - Frank B Hu
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.,Harvard Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Meir J Stampfer
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.,Harvard Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Iris Shai
- Faculty of Health Sciences, The Health & Nutrition Innovative International Research Center, Ben-Gurion University of the Negev, P.O. Box 653, 84105, Be'er Sheva, Israel. .,Department of Medicine, University of Leipzig, Leipzig, Germany. .,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
| |
Collapse
|
|
23
|
Fang S, Wade KH, Hughes DA, Fitzgibbon S, Yip V, Timpson NJ, Corbin LJ. A multivariant recall-by-genotype study of the metabolomic signature of BMI. Obesity (Silver Spring) 2022; 30:1298-1310. [PMID: 35598895 PMCID: PMC9324973 DOI: 10.1002/oby.23441] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 03/14/2022] [Accepted: 03/15/2022] [Indexed: 12/12/2022]
Abstract
OBJECTIVE This study estimated the effect of BMI on circulating metabolites in young adults using a recall-by-genotype study design. METHODS A recall-by-genotype study was implemented in the Avon Longitudinal Study of Parents and Children. Samples from 756 participants were selected for untargeted metabolomics analysis based on low versus high genetic liability for higher BMI defined by a genetic risk score (GRS). Regression analyses were performed to investigate associations between BMI GRS group and relative abundance of 973 metabolites. RESULTS After correction for multiple testing, 29 metabolites were associated with BMI GRS group. Bilirubin was among the most strongly associated metabolites, with reduced levels measured in individuals in the high-BMI GRS group (β = -0.32, 95% CI: -0.46 to -0.18, Benjamini-Hochberg adjusted p = 0.005). This study observed associations between BMI GRS group and the levels of several potentially diet-related metabolites, including hippurate, which had lower mean abundance in individuals in the high-BMI GRS group (β = -0.29, 95% CI: -0.44 to -0.15, Benjamini-Hochberg adjusted p = 0.008). CONCLUSIONS Together with existing literature, these results suggest that a genetic predisposition to higher BMI captures differences in metabolism leading to adiposity gain. In the absence of prospective data, separating these effects from the downstream consequences of weight gain is challenging.
Collapse
Affiliation(s)
- Si Fang
- MRC Integrative Epidemiology Unit at the University of BristolBristolUK
- Population Health ScienceBristol Medical SchoolUniversity of BristolBristolUK
| | - Kaitlin H. Wade
- MRC Integrative Epidemiology Unit at the University of BristolBristolUK
- Population Health ScienceBristol Medical SchoolUniversity of BristolBristolUK
| | - David A. Hughes
- MRC Integrative Epidemiology Unit at the University of BristolBristolUK
- Population Health ScienceBristol Medical SchoolUniversity of BristolBristolUK
| | - Sophie Fitzgibbon
- Bristol Bioresource LaboratoriesPopulation Health ScienceBristol Medical SchoolUniversity of BristolBristolUK
| | - Vikki Yip
- Bristol Bioresource LaboratoriesPopulation Health ScienceBristol Medical SchoolUniversity of BristolBristolUK
| | - Nicholas J. Timpson
- MRC Integrative Epidemiology Unit at the University of BristolBristolUK
- Population Health ScienceBristol Medical SchoolUniversity of BristolBristolUK
| | - Laura J. Corbin
- MRC Integrative Epidemiology Unit at the University of BristolBristolUK
- Population Health ScienceBristol Medical SchoolUniversity of BristolBristolUK
| |
Collapse
|
|
24
|
Meyer KA, Memili A, Jacobs DR, Gordon-Larsen P. Unraveling disease pathways involving the gut microbiota: the need for deep phenotyping and longitudinal data. Am J Clin Nutr 2022; 115:1261-1262. [PMID: 35354202 DOI: 10.1093/ajcn/nqac052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Katie A Meyer
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.,Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Aylin Memili
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - David R Jacobs
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA
| | - Penny Gordon-Larsen
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.,Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| |
Collapse
|
|
25
|
Gegner HM, Mechtel N, Heidenreich E, Wirth A, Cortizo FG, Bennewitz K, Fleming T, Andresen C, Freichel M, Teleman AA, Kroll J, Hell R, Poschet G. Deep Metabolic Profiling Assessment of Tissue Extraction Protocols for Three Model Organisms. Front Chem 2022; 10:869732. [PMID: 35548679 PMCID: PMC9083328 DOI: 10.3389/fchem.2022.869732] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Accepted: 04/05/2022] [Indexed: 12/12/2022] Open
Abstract
Metabolic profiling harbors the potential to better understand various disease entities such as cancer, diabetes, Alzheimer's, Parkinson's disease or COVID-19. To better understand such diseases and their intricate metabolic pathways in human studies, model animals are regularly used. There, standardized rearing conditions and uniform sampling strategies are prerequisites towards a successful metabolomic study that can be achieved through model organisms. Although metabolomic approaches have been employed on model organisms before, no systematic assessment of different conditions to optimize metabolite extraction across several organisms and sample types has been conducted. We address this issue using a highly standardized metabolic profiling assay analyzing 630 metabolites across three commonly used model organisms (Drosophila, mouse, and zebrafish) to find an optimal extraction protocol for various matrices. Focusing on parameters such as metabolite coverage, concentration and variance between replicates we compared seven extraction protocols. We found that the application of a combination of 75% ethanol and methyl tertiary-butyl ether (MTBE), while not producing the broadest coverage and highest concentrations, was the most reproducible extraction protocol. We were able to determine up to 530 metabolites in mouse kidney samples, 509 in mouse liver, 422 in zebrafish and 388 in Drosophila and discovered a core overlap of 261 metabolites in these four matrices. To enable other scientists to search for the most suitable extraction protocol in their experimental context and interact with this comprehensive data, we have integrated our data set in the open-source shiny app "MetaboExtract". Hereby, scientists can search for metabolites or compound classes of interest, compare them across the different tested extraction protocols and sample types as well as find reference concentration values.
Collapse
Affiliation(s)
- Hagen M. Gegner
- Metabolomics Core Technology Platform, Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany
| | - Nils Mechtel
- Metabolomics Core Technology Platform, Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany
| | - Elena Heidenreich
- Metabolomics Core Technology Platform, Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany
| | - Angela Wirth
- Institute of Pharmacology, Heidelberg University, Heidelberg, Germany
| | - Fabiola Garcia Cortizo
- Division of Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Katrin Bennewitz
- European Center for Angioscience (ECAS), Department of Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Thomas Fleming
- Department of Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany
| | - Carolin Andresen
- Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM GGmbH), Heidelberg, Germany
- Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany
- Faculty of Biosciences, Heidelberg University, Heidelberg, Germany
| | - Marc Freichel
- Institute of Pharmacology, Heidelberg University, Heidelberg, Germany
| | - Aurelio A. Teleman
- Division of Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jens Kroll
- European Center for Angioscience (ECAS), Department of Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Rüdiger Hell
- Metabolomics Core Technology Platform, Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany
| | - Gernot Poschet
- Metabolomics Core Technology Platform, Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany
| |
Collapse
|
|
26
|
Murthy VL, Nayor M, Carnethon M, Reis JP, Lloyd-Jones D, Allen NB, Kitchen R, Piaggi P, Steffen LM, Vasan RS, Freedman JE, Clish CB, Shah RV. Circulating metabolite profile in young adulthood identifies long-term diabetes susceptibility: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Diabetologia 2022; 65:657-674. [PMID: 35041022 PMCID: PMC8969893 DOI: 10.1007/s00125-021-05641-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 11/10/2021] [Indexed: 12/19/2022]
Abstract
AIMS/HYPOTHESIS The aim of this work was to define metabolic correlates and pathways of diabetes pathogenesis in young adults during a subclinical latent phase of diabetes development. METHODS We studied 2083 young adults of Black and White ethnicity in the prospective observational cohort Coronary Artery Risk Development in Young Adults (CARDIA) study (mean ± SD age 32.1 ± 3.6 years; 43.9% women; 42.7% Black; mean ± SD BMI 25.6 ± 4.9 kg/m2) and 1797 Framingham Heart Study (FHS) participants (mean ± SD age 54.7 ± 9.7 years; 52.1% women; mean ± SD BMI 27.4 ± 4.8 kg/m2), examining the association of comprehensive metabolite profiles with endophenotypes of diabetes susceptibility (adipose and muscle tissue phenotypes and systemic inflammation). Statistical learning techniques and Cox regression were used to identify metabolite signatures of incident diabetes over a median of nearly two decades of follow-up across both cohorts. RESULTS We identified known and novel metabolites associated with endophenotypes that delineate the complex pathophysiological architecture of diabetes, spanning mechanisms of muscle insulin resistance, inflammatory lipid signalling and beta cell metabolism (e.g. bioactive lipids, amino acids and microbe- and diet-derived metabolites). Integrating endophenotypes of diabetes susceptibility with the metabolome generated two multi-parametric metabolite scores, one of which (a proinflammatory adiposity score) was associated with incident diabetes across the life course in participants from both the CARDIA study (young adults; HR in a fully adjusted model 2.10 [95% CI 1.72, 2.55], p<0.0001) and FHS (middle-aged and older adults; HR 1.33 [95% CI 1.14, 1.56], p=0.0004). A metabolite score based on the outcome of diabetes was strongly related to diabetes in CARDIA study participants (fully adjusted HR 3.41 [95% CI 2.85, 4.07], p<0.0001) but not in the older FHS population (HR 1.15 [95% CI 0.99, 1.33], p=0.07). CONCLUSIONS/INTERPRETATION Selected metabolic abnormalities in young adulthood identify individuals with heightened diabetes risk independent of race, sex and traditional diabetes risk factors. These signatures replicate across the life course.
Collapse
Affiliation(s)
- Venkatesh L Murthy
- Department of Medicine and Radiology, University of Michigan, Ann Arbor, MI, USA.
| | - Matthew Nayor
- Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
| | | | - Jared P Reis
- National Heart, Lung, and Blood Institute, Bethesda, MD, USA
| | | | | | - Robert Kitchen
- Simches Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA
| | - Paolo Piaggi
- Department of Information Engineering, University of Pisa, Pisa, Italy
| | - Lyn M Steffen
- University of Minnesota School of Public Health, Minneapolis, MN, USA
| | - Ramachandran S Vasan
- Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, MA, USA
- Framingham Heart Study, Framingham, MA, USA
| | - Jane E Freedman
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Clary B Clish
- Broad Institute of Harvard and MIT, Cambridge, MA, USA
| | - Ravi V Shah
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
| |
Collapse
|
|
27
|
Little M, Dutta M, Li H, Matson A, Shi X, Mascarinas G, Molla B, Weigel K, Gu H, Mani S, Cui JY. Understanding the physiological functions of the host xenobiotic-sensing nuclear receptors PXR and CAR on the gut microbiome using genetically modified mice. Acta Pharm Sin B 2022; 12:801-820. [PMID: 35256948 PMCID: PMC8897037 DOI: 10.1016/j.apsb.2021.07.022] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 05/29/2021] [Accepted: 07/09/2021] [Indexed: 12/12/2022] Open
Abstract
Pharmacological activation of the xenobiotic-sensing nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) is well-known to increase drug metabolism and reduce inflammation. Little is known regarding their physiological functions on the gut microbiome. In this study, we discovered bivalent hormetic functions of PXR/CAR modulating the richness of the gut microbiome using genetically engineered mice. The absence of PXR or CAR increased microbial richness, and absence of both receptors synergistically increased microbial richness. PXR and CAR deficiency increased the pro-inflammatory bacteria Helicobacteraceae and Helicobacter. Deficiency in both PXR and CAR increased the relative abundance of Lactobacillus, which has bile salt hydrolase activity, corresponding to decreased primary taurine-conjugated bile acids (BAs) in feces, which may lead to higher internal burden of taurine and unconjugated BAs, both of which are linked to inflammation, oxidative stress, and cytotoxicity. The basal effect of PXR/CAR on the gut microbiome was distinct from pharmacological and toxicological activation of these receptors. Common PXR/CAR-targeted bacteria were identified, the majority of which were suppressed by these receptors. hPXR-TG mice had a distinct microbial profile as compared to wild-type mice. This study is the first to unveil the basal functions of PXR and CAR on the gut microbiome.
Collapse
Key Words
- BA, bile acid
- BSH, bile salt hydrolase
- Bile acids
- CA, cholic acid
- CAR
- CAR, constitutive androstane receptor
- CDCA, chenodeoxycholic acid
- CITCO, 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime
- CV, conventional
- CYP, cytochrome P450
- DCA, deoxycholic acid
- EGF, epidermal growth factor
- Feces
- GF, germ free
- GLP-1, glucagon-like peptide-1
- GM-CSF, granulocyte-macrophage colony-stimulating factor
- Gut microbiome
- HDCA, hyodeoxycholic acid
- IBD, inflammatory bowel disease
- IFNγ, interferon-gamma
- IL, interleukin
- IS, internal standards
- Inflammation
- LCA, lithocholic acid
- LC–MS/MS, liquid chromatography–tandem mass spectrometry
- MCA, muricholic acid
- MCP-1, monocyte chemoattractant protein-1
- Mice
- NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells
- NSAID, non-steroidal anti-inflammatory drug
- Nuclear receptor
- OH, hydroxylated
- OTUs, operational taxonomy units
- PA, indole-3 propionic acid
- PBDEs, polybrominated diphenyl ethers
- PCBs, polychlorinated biphenyls
- PCoA, Principle Coordinate Analysis
- PXR
- PXR, pregnane X receptor
- PiCRUSt, Phylogenetic Investigation of Communities by Reconstruction of Observed States
- QIIME, Quantitative Insights Into Microbial Ecology
- SCFAs, short-chain fatty acids
- SNP, single-nucleotide polymorphism
- SPF, specific-pathogen-free
- T, wild type
- T-, taurine conjugated
- TCPOBOP, 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene, 3,3′,5,5′-Tetrachloro-1,4-bis(pyridyloxy)benzene
- TGR-5, Takeda G-protein-coupled receptor 5
- TLR4, toll-like receptor 4
- TNF, tumor necrosis factor
- UDCA, ursodeoxycholic acid
- YAP, yes-associated protein
- hPXR-TG, humanized PXR transgenic
Collapse
Affiliation(s)
- Mallory Little
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA
| | - Moumita Dutta
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA
| | - Hao Li
- Department of Medicine, Molecular Pharmacology and Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Adam Matson
- University of Connecticut, Hartford, CT 06106, USA
| | - Xiaojian Shi
- Arizona Metabolomics Laboratory, College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA
| | - Gabby Mascarinas
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA
| | - Bruk Molla
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA
| | - Kris Weigel
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA
| | - Haiwei Gu
- Arizona Metabolomics Laboratory, College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA
| | - Sridhar Mani
- Department of Medicine, Molecular Pharmacology and Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Julia Yue Cui
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA
| |
Collapse
|
|
28
|
Andraos S, Beck KL, Jones MB, Han TL, Conlon CA, de Seymour JV. Characterizing patterns of dietary exposure using metabolomic profiles of human biospecimens: a systematic review. Nutr Rev 2022; 80:699-708. [PMID: 35024860 DOI: 10.1093/nutrit/nuab103] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
CONTEXT Establishing diet-disease associations requires reliable assessment of dietary intake. With the rapid advancement of metabolomics, its use in identifying objective biomarkers of dietary exposure has substantially increased. OBJECTIVE The aim of our review was to systematically combine all observational studies linking dietary intake patterns with metabolomic profiles of human biospecimens. DATA SOURCES Five databases were searched - MEDLINE, Embase, Scopus, Web of Science, and Cochrane CENTRAL - to March 2020. DATA EXTRACTION Of the 14 328 studies initially screened, 35 observational studies that met the specified inclusion criteria were included. DATA ANALYSIS All reviewed studies indicated that metabolomic measures were significantly correlated with dietary patterns, demonstrating the potential for using objective metabolomic measures to characterize individuals' dietary intake. However, similar dietary patterns did not always result in similar metabolomic profiles across different study populations. CONCLUSION Metabolomic profiles reflect a multitude of factors, including diet, genetic, phenotypic, and environmental influences, thereby providing a more comprehensive picture of the impact of diet on metabolism and health outcomes. Further exploration of dietary patterns and metabolomic profiles across different population groups is warranted.
Collapse
Affiliation(s)
- Stephanie Andraos
- S. Andraos, K.L. Beck, C.A. Conlon, and J.V. de Seymour are with the School of Sport, Exercise and Nutrition, College of Health, Massey University, Auckland, New Zealand. M.B. Jones is with the Department of Statistics, Faculty of Science, University of Auckland, Auckland, New Zealand. T.-L. Han is with the Department of Obstetrics and Gynaecology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Kathryn Louise Beck
- S. Andraos, K.L. Beck, C.A. Conlon, and J.V. de Seymour are with the School of Sport, Exercise and Nutrition, College of Health, Massey University, Auckland, New Zealand. M.B. Jones is with the Department of Statistics, Faculty of Science, University of Auckland, Auckland, New Zealand. T.-L. Han is with the Department of Obstetrics and Gynaecology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Mary Beatrix Jones
- S. Andraos, K.L. Beck, C.A. Conlon, and J.V. de Seymour are with the School of Sport, Exercise and Nutrition, College of Health, Massey University, Auckland, New Zealand. M.B. Jones is with the Department of Statistics, Faculty of Science, University of Auckland, Auckland, New Zealand. T.-L. Han is with the Department of Obstetrics and Gynaecology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ting-Li Han
- S. Andraos, K.L. Beck, C.A. Conlon, and J.V. de Seymour are with the School of Sport, Exercise and Nutrition, College of Health, Massey University, Auckland, New Zealand. M.B. Jones is with the Department of Statistics, Faculty of Science, University of Auckland, Auckland, New Zealand. T.-L. Han is with the Department of Obstetrics and Gynaecology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Cathryn Anne Conlon
- S. Andraos, K.L. Beck, C.A. Conlon, and J.V. de Seymour are with the School of Sport, Exercise and Nutrition, College of Health, Massey University, Auckland, New Zealand. M.B. Jones is with the Department of Statistics, Faculty of Science, University of Auckland, Auckland, New Zealand. T.-L. Han is with the Department of Obstetrics and Gynaecology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jamie Violet de Seymour
- S. Andraos, K.L. Beck, C.A. Conlon, and J.V. de Seymour are with the School of Sport, Exercise and Nutrition, College of Health, Massey University, Auckland, New Zealand. M.B. Jones is with the Department of Statistics, Faculty of Science, University of Auckland, Auckland, New Zealand. T.-L. Han is with the Department of Obstetrics and Gynaecology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| |
Collapse
|
|
29
|
Suskun C, Kilic O, Yilmaz Ciftdogan D, Guven S, Karbuz A, Ozkaya Parlakay A, Kara Y, Kacmaz E, Sahin A, Boga A, Kizmaz Isancli D, Gulhan B, Kanik-Yuksek S, Kiral E, Bozan G, Arslanoglu MO, Kizil MC, Dinleyici M, Us T, Varis A, Kaya M, Vandenplas Y, Dinleyici EC. Intestinal microbiota composition of children with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and multisystem inflammatory syndrome (MIS-C). Eur J Pediatr 2022; 181:3175-3191. [PMID: 35585256 PMCID: PMC9117086 DOI: 10.1007/s00431-022-04494-9] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 04/28/2022] [Accepted: 04/30/2022] [Indexed: 02/07/2023]
Abstract
UNLABELLED Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19. There are studies evaluating the microbiota composition at the time of diagnosis and during the course of COVID-19, especially in adults, while studies in children are limited and no study available in children with multisystem inflammatory syndrome in children (MIS-C). This study was planned to compare intestinal microbiota composition in children diagnosed with MIS-C and acute COVID-19 infection with healthy children. In this prospective multicenter study, 25 children diagnosed with MIS-C, 20 with COVID-19 infection, and 19 healthy children were included. Intestinal microbiota composition was evaluated by 16 s rRNA gene sequencing. We observed changes of diversity, richness, and composition of intestinal microbiota in MIS-C cases compared to COVID-19 cases and in the healthy controls. The Shannon index was higher in the MIS-C group than the healthy controls (p < 0.01). At phylum level, in the MIS-C group, a significantly higher relative abundance of Bacteroidetes and lower abundance of Firmicutes was found compared to the control group. Intestinal microbiota composition changed in MIS-C cases compared to COVID-19 and healthy controls, and Faecalibacterium prausnitzii decreased; Bacteroides uniformis, Bacteroides plebeius, Clostridium ramosum, Eubacterium dolichum, Eggerthella lenta, Bacillus thermoamylovorans, Prevotella tannerae, and Bacteroides coprophilus were dominant in children with MIS-C. At species level, we observed decreased Faecalibacterium prausnitzii, and increased Eubacterium dolichum, Eggerthella lenta, and Bacillus thermoamylovorans in children with MIS-C and increased Bifidobacterium adolescentis and Dorea formicigenerasus in the COVID-19 group. Our study is the first to evaluate the microbiota composition in MIS-C cases. There is a substantial change in the composition of the gut microbiota: (1) reduction of F. prausnitzii in children with MIS-C and COVID-19; (2) an increase of Eggerthella lenta which is related with autoimmunity; and (3) the predominance of E. dolichum is associated with metabolic dysfunctions and obesity in children with MIS-C. CONCLUSIONS Alterations of the intestinal microbiota might be part of pathogenesis of predisposing factor for MIS-C. It would be beneficial to conduct more extensive studies on the cause-effect relationship of these changes in microbiota composition and their effects on long-term prognosis. WHAT IS KNOWN • Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19. • However, the number of studies on children is limited, and no study on multisystem inflammatory syndrome in children is currently available (MIS-C). WHAT IS NEW • In individuals with MIS-C, the composition of the gut microbiota changed dramatically. • Decreased Faecalibacterium prausnitzii have been observed, increased Eggerthella lenta, which was previously linked to autoimmunity, and predominance of Eubacterium dolichum which was linked to metabolic dysfunction and obesity.
Collapse
Affiliation(s)
- Cansu Suskun
- grid.164274.20000 0004 0596 2460Department of Pediatrics, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, TR-26040 Turkey
| | - Omer Kilic
- grid.164274.20000 0004 0596 2460Department of Pediatric Infectious Disease, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey
| | - Dilek Yilmaz Ciftdogan
- grid.411795.f0000 0004 0454 9420Department of Pediatric Infectious Disease, Izmir Katip Celebi University Faculty of Medicine, Izmir, Turkey
| | - Sirin Guven
- grid.414850.c0000 0004 0642 8921Department of Pediatrics, Prof. Dr Ilhan Varank Training and Research Hospital, Istanbul, Turkey
| | - Adem Karbuz
- Department of Pediatric Infectious Disease, Dr. Cemil Tascioglu City Hospital, Istanbul, Turkey
| | - Aslinur Ozkaya Parlakay
- grid.512925.80000 0004 7592 6297Yildirim Beyazit University Faculty of Medicine Department of Pediatric Infectious Disease, Ankara City Hospital Department of Pediatric Infectious Disease, Ankara, Turkey
| | - Yalcın Kara
- grid.164274.20000 0004 0596 2460Department of Pediatric Infectious Disease, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey
| | - Ebru Kacmaz
- grid.164274.20000 0004 0596 2460Pediatric Intensive Care Unit, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey
| | - Aslihan Sahin
- grid.411795.f0000 0004 0454 9420Department of Pediatric Infectious Disease, Izmir Katip Celebi University Faculty of Medicine, Izmir, Turkey
| | - Aysun Boga
- grid.414850.c0000 0004 0642 8921Department of Pediatrics, Prof. Dr Ilhan Varank Training and Research Hospital, Istanbul, Turkey
| | - Didem Kizmaz Isancli
- Department of Pediatric Infectious Disease, Dr. Cemil Tascioglu City Hospital, Istanbul, Turkey
| | - Belgin Gulhan
- grid.512925.80000 0004 7592 6297Department of Pediatric Infectious Disease, Ankara City Hospital, Ankara, Turkey
| | - Saliha Kanik-Yuksek
- grid.512925.80000 0004 7592 6297Department of Pediatric Infectious Disease, Ankara City Hospital, Ankara, Turkey
| | - Eylem Kiral
- grid.164274.20000 0004 0596 2460Pediatric Intensive Care Unit, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey
| | - Gurkan Bozan
- grid.164274.20000 0004 0596 2460Pediatric Intensive Care Unit, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey
| | - Mehmet Ozgür Arslanoglu
- grid.164274.20000 0004 0596 2460Pediatric Intensive Care Unit, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey
| | - Mahmut Can Kizil
- grid.164274.20000 0004 0596 2460Department of Pediatric Infectious Disease, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey
| | - Meltem Dinleyici
- grid.164274.20000 0004 0596 2460Department of Social Pediatrics, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey
| | - Tercan Us
- grid.164274.20000 0004 0596 2460Department of Microbiology, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey
| | | | | | - Yvan Vandenplas
- grid.8767.e0000 0001 2290 8069KidZ Health Castle, UZ Brussels, Vrije Universiteit Brussel, Brussels, Belgium
| | - Ener Cagri Dinleyici
- grid.164274.20000 0004 0596 2460Department of Pediatrics, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, TR-26040 Turkey
| |
Collapse
|
|
30
|
Brial F, Chilloux J, Nielsen T, Vieira-Silva S, Falony G, Andrikopoulos P, Olanipekun M, Hoyles L, Djouadi F, Neves AL, Rodriguez-Martinez A, Mouawad GI, Pons N, Forslund S, Le-chatelier E, Le Lay A, Nicholson J, Hansen T, Hyötyläinen T, Clément K, Oresic M, Bork P, Ehrlich SD, Raes J, Pedersen OB, Gauguier D, Dumas ME. Human and preclinical studies of the host-gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health. Gut 2021; 70:2105-2114. [PMID: 33975870 PMCID: PMC8515120 DOI: 10.1136/gutjnl-2020-323314] [Citation(s) in RCA: 74] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 04/15/2021] [Accepted: 04/18/2021] [Indexed: 12/30/2022]
Abstract
OBJECTIVE Gut microbial products are involved in regulation of host metabolism. In human and experimental studies, we explored the potential role of hippurate, a hepatic phase 2 conjugation product of microbial benzoate, as a marker and mediator of metabolic health. DESIGN In 271 middle-aged non-diabetic Danish individuals, who were stratified on habitual dietary intake, we applied 1H-nuclear magnetic resonance (NMR) spectroscopy of urine samples and shotgun-sequencing-based metagenomics of the gut microbiome to explore links between the urine level of hippurate, measures of the gut microbiome, dietary fat and markers of metabolic health. In mechanistic experiments with chronic subcutaneous infusion of hippurate to high-fat-diet-fed obese mice, we tested for causality between hippurate and metabolic phenotypes. RESULTS In the human study, we showed that urine hippurate positively associates with microbial gene richness and functional modules for microbial benzoate biosynthetic pathways, one of which is less prevalent in the Bacteroides 2 enterotype compared with Ruminococcaceae or Prevotella enterotypes. Through dietary stratification, we identify a subset of study participants consuming a diet rich in saturated fat in which urine hippurate concentration, independently of gene richness, accounts for links with metabolic health. In the high-fat-fed mice experiments, we demonstrate causality through chronic infusion of hippurate (20 nmol/day) resulting in improved glucose tolerance and enhanced insulin secretion. CONCLUSION Our human and experimental studies show that a high urine hippurate concentration is a general marker of metabolic health, and in the context of obesity induced by high-fat diets, hippurate contributes to metabolic improvements, highlighting its potential as a mediator of metabolic health.
Collapse
Affiliation(s)
- François Brial
- UMRS 1124 INSERM, Université de Paris Descartes, Paris, France
| | - Julien Chilloux
- Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Trine Nielsen
- Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Kobenhavn, Denmark
| | - Sara Vieira-Silva
- Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
| | - Gwen Falony
- Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
| | - Petros Andrikopoulos
- Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK,National Heart & Lung Institute, Section of Genomic & Environmental Medicine, Imperial College London, London, UK
| | - Michael Olanipekun
- Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK,National Heart & Lung Institute, Section of Genomic & Environmental Medicine, Imperial College London, London, UK
| | - Lesley Hoyles
- Department of Biosciences, Nottingham Trent University, Nottingham, UK
| | - Fatima Djouadi
- Centre de Recherche des Cordeliers, Université Paris Descartes, Paris, France,Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Paris, France
| | - Ana L Neves
- Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Andrea Rodriguez-Martinez
- Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | | | - Nicolas Pons
- Metagenopolis, INRAE, Paris, Île-de-France, France
| | - Sofia Forslund
- Forslund Lab, Max Delbrück Centrum für Molekulare Medizin Experimental and Clinical Research Center, Berlin, Berlin, Germany
| | | | - Aurélie Le Lay
- UMRS 1124 INSERM, Université de Paris Descartes, Paris, France
| | - Jeremy Nicholson
- Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Torben Hansen
- Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Kobenhavn, Denmark
| | | | - Karine Clément
- INSERM, U1166, team 6 Nutriomique, Université Pierre et Marie Curie-Paris 6, Paris, France,Institute of Cardiometabolism and Nutrition (ICAN), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
| | - Matej Oresic
- School of Medical Sciences, Örebro Universitet, Orebro, Sweden
| | - Peer Bork
- Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Stanislav Dusko Ehrlich
- Metagenopolis, INRAE, Paris, Île-de-France, France,Center for Host Microbiome Interactions, King's College London Dental Institute, London, UK
| | - Jeroen Raes
- Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium,Center for Microbiology, Vlaams Instituut voor Biotechnologie, Leuven, Belgium
| | - Oluf Borbye Pedersen
- Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Kobenhavn, Denmark
| | - Dominique Gauguier
- UMRS 1124 INSERM, Université de Paris Descartes, Paris, France,McGill Genome Centre & Department of Human Genetics, McGill University, Montréal, Québec, Canada
| | - Marc-Emmanuel Dumas
- Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK .,National Heart & Lung Institute, Section of Genomic & Environmental Medicine, Imperial College London, London, UK.,McGill Genome Centre & Department of Human Genetics, McGill University, Montréal, Québec, Canada.,European Genomics Institute for Diabetes,INSERM U1283, CNRS UMR8199, Institut Pasteur de Lille, Lille University Hospital, Unversity of Lille, Lille, France
| |
Collapse
|
|
31
|
Wang X, Wu M. Research progress of gut microbiota and frailty syndrome. Open Med (Wars) 2021; 16:1525-1536. [PMID: 34712824 PMCID: PMC8511967 DOI: 10.1515/med-2021-0364] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 07/27/2021] [Accepted: 08/23/2021] [Indexed: 12/30/2022] Open
Abstract
Frailty is a clinical syndrome caused by homeostasis imbalance. It is characterized by marked vulnerability to endogenous or exogenous stressors, reduced self-care ability, and increased mortality risk. This aging-related syndrome is common in individuals older than 65 years and carries an increased risk for poor health outcomes. These include falls, incident disability, incapacity, and mortality. In addition, it can result in a poor prognosis for other comorbidities. With the aging population, frailty increases the burden of adverse health outcomes. Studies on frailty are at their infancy. In addition, there is a lack of thorough understanding of its pathogenesis. Several studies have suggested that frailty is caused by chronic inflammation due to enhanced intestinal permeability following gut microbiota imbalance as well as pathogen-related antibodies entering the circulation system. These result in musculoskeletal system disorders and neurodegenerative diseases. However, this assumption has not been validated in large cohort-based studies. Several studies have suggested that inflammation is not the only cause of frailty. Hence, further studies are necessary to extend our understanding of its pathogenesis. This review summarizes the research findings in the field and expands on the possible role of the gut microbiota in frailty syndrome.
Collapse
Affiliation(s)
- Xiao Wang
- Geriatrics Department, Zhejiang Hospital, Hangzhou 310013, China
| | - Min Wu
- Geriatrics Department, Zhejiang Hospital, Hangzhou 310013, China
| |
Collapse
|
|
32
|
Cheng TY, Li JX, Chen JY, Chen PY, Ma LR, Zhang GL, Yan PY. Gut microbiota: a potential target for traditional Chinese medicine intervention in coronary heart disease. Chin Med 2021; 16:108. [PMID: 34686199 PMCID: PMC8540100 DOI: 10.1186/s13020-021-00516-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 10/06/2021] [Indexed: 02/06/2023] Open
Abstract
Coronary heart disease (CHD) is a common ischaemic heart disease whose pathological mechanism has not been fully elucidated. Single target drugs, such as antiplatelet aggregation, coronary artery dilation and lipid-lowering medicines, can relieve some symptoms clinically but cannot effectively prevent and treat CHD. Accumulating evidence has revealed that alterations in GM composition, diversity, and richness are associated with the risk of CHD. The metabolites of the gut microbiota (GM), including trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs) and bile acids (BAs), affect human physiology by activating numerous signalling pathways. Due to the advantage of multiple components and multiple targets, traditional Chinese medicine (TCM) can intervene in CHD by regulating the composition of the GM, reducing TMAO, increasing SCFAs and other CHD interventions. We have searched PubMed, Web of science, Google Scholar Science Direct, and China National Knowledge Infrastructure (CNKI), with the use of the keywords "gut microbiota, gut flora, traditional Chinese medicine, herbal medicine, coronary heart disease". This review investigated the relationship between GM and CHD, as well as the intervention of TCM in CHD and GM, and aims to provide valuable insights for the treatments of CHD by TCM.
Collapse
Affiliation(s)
- Tian-Yi Cheng
- Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, People's Republic of China
| | - Jia-Xin Li
- Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, People's Republic of China
| | - Jing-Yi Chen
- Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, People's Republic of China
| | - Pei-Ying Chen
- Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, People's Republic of China
| | - Lin-Rui Ma
- Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, People's Republic of China
| | - Gui-Lin Zhang
- Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, People's Republic of China.
| | - Pei-Yu Yan
- Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, People's Republic of China.
| |
Collapse
|
|
33
|
Bahrampour N, Mirzababaei A, Shiraseb F, Clark CCT, Mirzaei K. The mediatory role of inflammatory markers on the relationship between dietary energy density and body composition among obese and overweight adult women: A cross-sectional study. Int J Clin Pract 2021; 75:e14579. [PMID: 34185366 DOI: 10.1111/ijcp.14579] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 06/25/2021] [Indexed: 01/25/2023] Open
Abstract
AIMS Energy density (ED) is known to influence body composition (BC). Indeed, consumption of high ED foods can increase body fat mass (BFM) and inflammatory markers. We sought to assess the mediatory role of high-sensitive-C-reactive protein (hs-CRP), transforming growth factor-β (TGF-beta), and plasminogen activator inhibitor-1 (PAI-1) on the relationship between ED and BC in women with overweight/obesity. METHODS This was a cross-sectional study consisting of 391 women. Body composition (Bioelectrical Impedance Analysis) and a food frequency questionnaire (FFQ) was used to assess the BC and food intake of individuals. Blood samples and serum level of hs-CRP, PAI-1, and TGF-β were collected. ED per one gram of foods was calculated and divided to quartiles. Linear logistic regression was used to investigate the association between BC across quartiles of ED intake. RESULTS Total body water (TBW), fat free mass (FFM), visceral fat area (VFA), and fat free mass index (FFMI) appeared to be mediated by hs-CRP across ED quartiles. TBW, FFM with PAI-1, bone mineral content (BMC) with PAI-1 and TGF-beta, and skeletal lean mass (SLM) were inversely associated with hs-CRP, respectively. Fat trunk, TBW, BFM, FFM, SLM, waist circumference (WC), FFMI, and FMI were positively mediated by TGF-beta with increasing ED food intakes. Fat trunk, BFM, SLM, WC, FFMI and FMI were positively mediated by PAI-1. CONCLUSIONS Most BC subcategories were positively associated with higher ED intake, mediated by increasing serum levels of PAI-1 and TGF-beta. Moreover, higher serum hs-CRP levels may be related to body fat and water alteration concomitant to a higher ED intake.
Collapse
Affiliation(s)
- Niki Bahrampour
- Department of Nutrition, Science and Research Branch, Islamic Azad University (SRBIAU), Tehran, Iran
| | - Atieh Mirzababaei
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Farideh Shiraseb
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Cain C T Clark
- Centre for Intelligent Healthcare, Coventry University, Coventry, UK
| | - Khadijeh Mirzaei
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| |
Collapse
|
|
34
|
Žiberna L, Jenko-Pražnikar Z, Petelin A. Serum Bilirubin Levels in Overweight and Obese Individuals: The Importance of Anti-Inflammatory and Antioxidant Responses. Antioxidants (Basel) 2021; 10:antiox10091352. [PMID: 34572984 PMCID: PMC8472302 DOI: 10.3390/antiox10091352] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 08/22/2021] [Accepted: 08/23/2021] [Indexed: 12/14/2022] Open
Abstract
Obesity is a chronic condition involving low-grade inflammation and increased oxidative stress; thus, obese and overweight people have lower values of serum bilirubin. Essentially, bilirubin is a potent endogenous antioxidant molecule with anti-inflammatory, immunomodulatory, antithrombotic, and endocrine properties. This review paper presents the interplay between obesity-related pathological processes and bilirubin, with a focus on adipose tissue and adipokines. We discuss potential strategies to mildly increase serum bilirubin levels in obese patients as an adjunctive therapeutic approach.
Collapse
Affiliation(s)
- Lovro Žiberna
- Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia;
| | | | - Ana Petelin
- Faculty of Health Sciences, University of Primorska, SI-6310 Izola, Slovenia;
- Correspondence: ; Tel.: +386-5-66-2469
| |
Collapse
|
|
35
|
Cunningham AL, Stephens JW, Harris DA. A review on gut microbiota: a central factor in the pathophysiology of obesity. Lipids Health Dis 2021; 20:65. [PMID: 34233682 PMCID: PMC8262044 DOI: 10.1186/s12944-021-01491-z] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 06/17/2021] [Indexed: 12/13/2022] Open
Abstract
Obesity and its complications constitute a substantial burden. Considerable published research describes the novel relationships between obesity and gut microbiota communities. It is becoming evident that microbiota behave in a pivotal role in their ability to influence homeostatic mechanisms either to the benefit or detriment of host health, the extent of which is not fully understood. A greater understanding of the contribution of gut microbiota towards host pathophysiology is revealing new therapeutic avenues to tackle the global obesity epidemic. This review focuses on causal relationships and associations with obesity, proposed central mechanisms encouraging the development of obesity and promising prospective methods for microbiota manipulation.
Collapse
Affiliation(s)
- A L Cunningham
- Department of Surgery, Swansea Bay University Health Board, Swansea, SA2 8QA, UK. .,Swansea University Medical School, Swansea University, Swansea, SA2 8QA, UK.
| | - J W Stephens
- Swansea University Medical School, Swansea University, Swansea, SA2 8QA, UK
| | - D A Harris
- Department of Surgery, Swansea Bay University Health Board, Swansea, SA2 8QA, UK.,Swansea University Medical School, Swansea University, Swansea, SA2 8QA, UK
| |
Collapse
|
|
36
|
Toni T, Alverdy J. Harnessing the Microbiome to Optimize Surgical Outcomes in the COVID-19 Era. ANNALS OF SURGERY OPEN 2021; 2:e056. [PMID: 36590034 PMCID: PMC9794001 DOI: 10.1097/as9.0000000000000056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Accepted: 02/18/2021] [Indexed: 01/04/2023] Open
Abstract
In this era of testing uncertainties, changing guidelines, and incomplete knowledge, "clearing" patients for surgery in the time of SARS-COVID-19 has been met with various challenges. Efforts to increase patient fitness have long been at the forefront of surgical practicing guidelines, but the current climate requires a renewed sense of focus on these measures. It is essential to understand how dietary history, previous antibiotic exposure, and baseline microbiota can inform and optimize preoperative and postoperative management of the surgical patient in the time of COVID-19. This piece focuses on the clinical, molecular, and physiologic dynamics that occur in preparing patients for surgery during COVID-19, considering the physiologic stress inherent in the procedure itself and the importance of specialized perioperative management approaches. COVID-19 has created a renewed sense of urgency to maintain our discipline in implementing those practices that have long been confirmed to be beneficial to patient outcome. This practice, along with a renewed interest in understanding how the gut microbiome is affected by the confinement, social distancing, etc., due to the COVID pandemic, is ever more important. Therefore, here we discuss the microbiome's role as a defense against viral infection and its potential for reactivation during the process of surgery as the next frontier for surgical advancement.
Collapse
Affiliation(s)
- Tiffany Toni
- From the Pritzker School of Medicine, University of Chicago, Chicago, IL
| | - John Alverdy
- From the Pritzker School of Medicine, University of Chicago, Chicago, IL
| |
Collapse
|
|
37
|
The Influence of Diet and Sex on the Gut Microbiota of Lean and Obese JCR:LA- cp Rats. Microorganisms 2021; 9:microorganisms9051037. [PMID: 34066029 PMCID: PMC8151891 DOI: 10.3390/microorganisms9051037] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 05/04/2021] [Accepted: 05/07/2021] [Indexed: 12/13/2022] Open
Abstract
There is an increased interest in the gut microbiota as it relates to health and obesity. The impact of diet and sex on the gut microbiota in conjunction with obesity also demands extensive systemic investigation. Thus, the influence of sex, diet, and flaxseed supplementation on the gut microbiota was examined in the JCR:LA-cp rat model of genetic obesity. Male and female obese rats were randomized into four groups (n = 8) to receive, for 12 weeks, either (a) control diet (Con), (b) control diet supplemented with 10% ground flaxseed (CFlax), (c) a high-fat, high sucrose (HFHS) diet, or (d) HFHS supplemented with 10% ground flaxseed (HFlax). Male and female JCR:LA-cp lean rats served as genetic controls and received similar dietary interventions. Illumine MiSeq sequencing revealed a richer microbiota in rats fed control diets rather than HFHS diets. Obese female rats had lower alpha-diversity than lean female; however, both sexes of obese and lean JCR rats differed significantly in β-diversity, as their gut microbiota was composed of different abundances of bacterial types. The feeding of an HFHS diet affected the diversity by increasing the phylum Bacteroidetes and reducing bacterial species from phylum Firmicutes. Fecal short-chain fatty acids such as acetate, propionate, and butyrate-producing bacterial species were correspondingly impacted by the HFHS diet. Flax supplementation improved the gut microbiota by decreasing the abundance of Blautia and Eubacterium dolichum. Collectively, our data show that an HFHS diet results in gut microbiota dysbiosis in a sex-dependent manner. Flaxseed supplementation to the diet had a significant impact on gut microbiota diversity under both flax control and HFHS dietary conditions.
Collapse
|
|
38
|
Zhao L, Zhu X, Xia M, Li J, Guo AY, Zhu Y, Yang X. Quercetin Ameliorates Gut Microbiota Dysbiosis That Drives Hypothalamic Damage and Hepatic Lipogenesis in Monosodium Glutamate-Induced Abdominal Obesity. Front Nutr 2021; 8:671353. [PMID: 33996881 PMCID: PMC8116593 DOI: 10.3389/fnut.2021.671353] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 04/01/2021] [Indexed: 12/12/2022] Open
Abstract
Monosodium glutamate (MSG)-induced abdominal obesity, conventionally caused by hypothalamic damage, is a critical risk factor for health problem. Microbiota-gut-brain axis plays important roles in a variety of metabolic diseases. However, whether gut microbiota is involved in the pathogenesis for MSG-induced abdominal obesity and the effect of quercetin on it remains unclear. Herein, we find that MSG-induced gut microbiota dysbiosis contributes to neuronal damage in the hypothalamus, as indicated by antibiotics-induced microbiota depletion and co-house treatment. Inspired by this finding, we investigate the mechanism in-depth for MSG-induced abdominal obesity. Liver transcriptome profiling shows retinol metabolism disorder in MSG-induced abdominal obese mice. In which, retinol saturase (RetSat) in the liver is notably up-regulated, and the downstream lipogenesis is correspondingly elevated. Importantly, microbiota depletion or co-house treatment eliminates the difference of RetSat expression in the liver, indicating gut microbiota changes are responsible for liver retinol metabolism disorder. Moreover, this study finds dietary quercetin could modulate MSG-induced gut microbiota dysbiosis, alleviate hypothalamic damage and down-regulate liver RetSat expression, thus ameliorating abdominal obesity. Our study enriches the pathogenesis of MSG-induced abdominal obesity and provides a prebiotic agent to ameliorate abdominal obesity.
Collapse
Affiliation(s)
- Lijun Zhao
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoqiang Zhu
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Mengxuan Xia
- Key Laboratory of Molecular Biophysics of the Ministry of Education, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Li
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - An-Yuan Guo
- Key Laboratory of Molecular Biophysics of the Ministry of Education, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Yanhong Zhu
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Xiangliang Yang
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| |
Collapse
|
|
39
|
Pietzner M, Budde K, Rühlemann M, Völzke H, Homuth G, Weiss FU, Lerch MM, Frost F. Exocrine Pancreatic Function Modulates Plasma Metabolites Through Changes in Gut Microbiota Composition. J Clin Endocrinol Metab 2021; 106:e2290-e2298. [PMID: 33462612 PMCID: PMC8186556 DOI: 10.1210/clinem/dgaa961] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Indexed: 02/08/2023]
Abstract
PURPOSE Exocrine pancreatic function is critically involved in regulating the gut microbiota composition. At the same time, its impairment acutely affects human metabolism. How these 2 roles are connected is unknown. We studied how the exocrine pancreas contributes to metabolism via modulation of gut microbiota. DESIGN Fecal samples were collected in 2226 participants of the population-based Study of Health in Pomerania (SHIP/SHIP-TREND) to determine exocrine pancreatic function (pancreatic elastase enzyme-linked immunosorbent assay) and intestinal microbiota profiles (16S ribosomal ribonucleic acid gene sequencing). Plasma metabolite levels were determined by mass spectrometry. RESULTS Exocrine pancreatic function was associated with changes in the abundance of 28 taxa and, simultaneously, with those of 16 plasma metabolites. Mediation pathway analysis revealed that a significant component of how exocrine pancreatic function affects the blood metabolome is mediated via gut microbiota abundance changes, most prominently, circulating serotonin and lysophosphatidylcholines. CONCLUSION These results imply that the effect of exocrine pancreatic function on intestinal microbiota composition alters the availability of microbial-derived metabolites in the blood and thus directly contributes to the host metabolic changes associated with exocrine pancreatic dysfunction.
Collapse
Affiliation(s)
- Maik Pietzner
- Institute of Clinical Chemistry and Laboratory Medicine, University
Medicine Greifswald, Greifswald, Germany
| | - Kathrin Budde
- Institute of Clinical Chemistry and Laboratory Medicine, University
Medicine Greifswald, Greifswald, Germany
| | - Malte Rühlemann
- Institute of Clinical Molecular Biology, Christian Albrechts University
of Kiel, Kiel, Germany
| | - Henry Völzke
- Institute for Community Medicine, University Medicine
Greifswald, Greifswald, Germany
| | - Georg Homuth
- Department of Functional Genomics, Interfaculty Institute for Genetics
and Functional Genomics, University Medicine Greifswald,
Greifswald, Germany
| | - Frank U Weiss
- Department of Medicine A, University Medicine Greifswald,
Greifswald, Germany
| | - Markus M Lerch
- Department of Medicine A, University Medicine Greifswald,
Greifswald, Germany
- Correspondence and Reprint Requests: Markus M. Lerch MD, Department of Medicine A, University Medicine
Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, Germany.
| | - Fabian Frost
- Department of Medicine A, University Medicine Greifswald,
Greifswald, Germany
| |
Collapse
|
|
40
|
Coker MO, Laue HE, Hoen AG, Hilliard M, Dade E, Li Z, Palys T, Morrison HG, Baker E, Karagas MR, Madan JC. Infant Feeding Alters the Longitudinal Impact of Birth Mode on the Development of the Gut Microbiota in the First Year of Life. Front Microbiol 2021; 12:642197. [PMID: 33897650 PMCID: PMC8059768 DOI: 10.3389/fmicb.2021.642197] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 02/22/2021] [Indexed: 12/15/2022] Open
Abstract
Cesarean-delivered (CD) infants harbor a distinct gut microbiome from vaginally delivered (VD) infants, however, during infancy, the most important driver of infant gut microbial colonization is infant feeding. Earlier studies have shown that breastfeeding is associated with higher levels of health-promoting bacteria such and Bifidobacterium and Bacteroides via modulation of the immune system, and production of metabolites. As the infant gut matures and solid foods are introduced, it is unclear whether longer duration of breast feeding restore loss of beneficial taxa within the intestinal microbiota of operatively delivered infants. Within the New Hampshire Birth Cohort Study, we evaluated the longitudinal effect of delivery mode and infant feeding on the taxonomic composition and functional capacity of developing gut microbiota in the First year of life. Microbiota of 500 stool samples collected between 6 weeks and 12 months of age (from 229 infants) were characterized by 16S ribosomal RNA sequencing. Shotgun metagenomic sequencing was also performed on 350 samples collected at either 6 weeks or 12 months of age. Among infant participants, 28% were cesarean-delivered (CD) infants and most (95%) initiated breastfeeding within the first six months of life, with 26% exclusively breastfed and 69% mixed-fed (breast milk and formula), in addition to complementary foods by age 1. Alpha (within-sample) diversity was significantly lower in CD infants compared to vaginally delivered (VD) infants (P < 0.05) throughout the study period. Bacterial community composition clustering by both delivery mode and feeding duration at 1 year of age revealed that CD infants who were breast fed for < 6 months were more dissimilar to VD infants than CD infants who breast fed for ≥ 6 months. We observed that breastfeeding modified the longitudinal impact of delivery mode on the taxonomic composition of the microbiota by 1 year of age, with an observed increase in abundance of Bacteroides fragilis and Lactobacillus with longer duration of breastfeeding among CD infants while there was an increase in Faecalibacterium for VD infants. Our findings confirm that duration of breastfeeding plays a critical role in restoring a health-promoting microbiome, call for further investigations regarding the association between breast milk exposure and health outcomes in early life.
Collapse
Affiliation(s)
- Modupe O. Coker
- Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- School of Dental Medicine, School of Public Health at Rutgers, Newark, NJ, United States
| | - Hannah E. Laue
- Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
| | - Anne G. Hoen
- Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- Center for Molecular Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- Children’s Environmental Health & Disease Prevention Research Center at Dartmouth, Hanover, NH, United States
| | - Margaret Hilliard
- Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
| | - Erika Dade
- Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
| | - Zhigang Li
- Department of Biostatistics, University of Florida, Gainsville, FL, United States
| | - Thomas Palys
- Children’s Environmental Health & Disease Prevention Research Center at Dartmouth, Hanover, NH, United States
| | - Hilary G. Morrison
- Marine Biological Laboratory, Josephine Bay Paul Center, Woods Hole, MA, United States
| | - Emily Baker
- Department of Pediatrics, Children’s Hospital at Dartmouth, Lebanon, NH, United States
| | - Margaret R. Karagas
- Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- Center for Molecular Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- Children’s Environmental Health & Disease Prevention Research Center at Dartmouth, Hanover, NH, United States
| | - Juliette C. Madan
- Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- Children’s Environmental Health & Disease Prevention Research Center at Dartmouth, Hanover, NH, United States
- Department of Pediatrics, Children’s Hospital at Dartmouth, Lebanon, NH, United States
| |
Collapse
|
|
41
|
Klancic T, Laforest-Lapointe I, Wong J, Choo A, Nettleton JE, Chleilat F, Arrieta MC, Reimer RA. Concurrent Prebiotic Intake Reverses Insulin Resistance Induced by Early-Life Pulsed Antibiotic in Rats. Biomedicines 2021; 9:biomedicines9010066. [PMID: 33445530 PMCID: PMC7827688 DOI: 10.3390/biomedicines9010066] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 12/23/2020] [Accepted: 01/08/2021] [Indexed: 12/22/2022] Open
Abstract
Pulsed antibiotic treatment (PAT) early in life increases risk of obesity. Prebiotics can reduce fat mass and improve metabolic health. We examined if co-administering prebiotic with PAT reduces obesity risk in rat pups weaned onto a high fat/sucrose diet. Pups were randomized to (1) control [CTR], (2) antibiotic [ABT] (azithromycin), (3) prebiotic [PRE] (10% oligofructose (OFS)), (4) antibiotic + prebiotic [ABT + PRE]. Pulses of antibiotics/prebiotics were administered at d19-21, d28-30 and d37-39. Male and female rats given antibiotics (ABT) had higher body weight than all other groups at 10 wk of age. The PAT phenotype was stronger in ABT males than females, where increased fat mass, hyperinsulinemia and insulin resistance were present and all reversible with prebiotics. Reduced hypothalamic and hepatic expression of insulin receptor substrates and ileal tight junction proteins was seen in males only, explaining their greater insulin resistance. In females, insulin resistance was improved with prebiotics and normalized to lean control. ABT reduced Lactobacillaceae and increased Bacteroidaceae in both sexes. Using a therapeutic dose of an antibiotic commonly used for acute infection in children, PAT increased body weight and impaired insulin production and insulin sensitivity. The effects were reversed with prebiotic co-administration in a sex-specific manner.
Collapse
Affiliation(s)
- Teja Klancic
- Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, Canada; (T.K.); (J.W.); (A.C.); (J.E.N.); (F.C.)
| | - Isabelle Laforest-Lapointe
- Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; (I.L.-L.); (M.-C.A.)
- Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada
| | - Jolene Wong
- Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, Canada; (T.K.); (J.W.); (A.C.); (J.E.N.); (F.C.)
| | - Ashley Choo
- Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, Canada; (T.K.); (J.W.); (A.C.); (J.E.N.); (F.C.)
| | - Jodi E. Nettleton
- Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, Canada; (T.K.); (J.W.); (A.C.); (J.E.N.); (F.C.)
| | - Faye Chleilat
- Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, Canada; (T.K.); (J.W.); (A.C.); (J.E.N.); (F.C.)
| | - Marie-Claire Arrieta
- Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; (I.L.-L.); (M.-C.A.)
- Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada
| | - Raylene A. Reimer
- Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, Canada; (T.K.); (J.W.); (A.C.); (J.E.N.); (F.C.)
- Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada
- Correspondence: ; Tel.: +1-403-220-8218
| |
Collapse
|
|
42
|
Fu C, Yang Y, Kumrungsee T, Kimoto A, Izu H, Kato N. Low-Dose Ethanol Has Impacts on Plasma Levels of Metabolites Relating to Chronic Disease Risk in SAMP8 mice. J Nutr Sci Vitaminol (Tokyo) 2021; 66:553-560. [PMID: 33390397 DOI: 10.3177/jnsv.66.553] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
The effects of low-dose alcohol on experimental animals are unclear. This study examined plasma metabolites in senescence-accelerated mice 8 (SAMP8) given low-dose ethanol, and compared them with aging progress and skeletal muscle strength. Male SAMP8 mice (10-wk-old) were given drinking water containing 0% (control), 1%, 2%, or 5% (v/v) ethanol for 14 wk. Compared with the control group, only mice who consumed 1% ethanol experienced a lower senescence score at 18 and 23 wk, as well as an increased limb grip strength at 21 wk. Plasma metabolites of control, 1% and 2% ethanol groups were analyzed by capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF/MS). Among the 7 metabolites affected by ethanol, notewhorthy is the positive association of the ethanol levels in drinking water with the levels of α-ketoglutarate (antioxidant and anti-inflammatory metabolite) and hippurate (antioxidant and microbial co-metabolite) (p<0.05). Intriguingly, the levels of 2-hydroxyisobutyrate (the biomarker of energy metabolism and microbial co-metabolite) were higher in the 1% ethanol group (p<0.05), but not in the 2% ethanol group as compared to the control. Furthermore, the levels of some of the metabolites affected were correlated with some variables in the grading score of senescence and muscle strength. This study provides a novel insight into how low-dose ethanol in SAMP8 mice modulates the levels of circulating metabolites relating to chronic disease risk.
Collapse
Affiliation(s)
- Churan Fu
- Graduate School of Integrated Sciences for Life, Hiroshima University
| | - Yongshou Yang
- Graduate School of Integrated Sciences for Life, Hiroshima University
| | | | - Akiko Kimoto
- Faculty of Human Ecology, Yasuda Women's University
| | - Hanae Izu
- Quality and Evaluation Research Division, National Research Institute of Brewing
| | - Norihisa Kato
- Graduate School of Integrated Sciences for Life, Hiroshima University
| |
Collapse
|
|
43
|
Haran JP, McCormick BA. Aging, Frailty, and the Microbiome-How Dysbiosis Influences Human Aging and Disease. Gastroenterology 2021; 160:507-523. [PMID: 33307030 PMCID: PMC7856216 DOI: 10.1053/j.gastro.2020.09.060] [Citation(s) in RCA: 94] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Revised: 09/08/2020] [Accepted: 09/16/2020] [Indexed: 02/07/2023]
Abstract
The human gut microbiome is a collection of bacteria, protozoa, fungi, and viruses that coexist in our bodies and are essential in protective, metabolic, and physiologic functions of human health. Gut dysbiosis has traditionally been linked to increased risk of infection, but imbalances within the intestinal microbial community structure that correlate with untoward inflammatory responses are increasingly recognized as being involved in disease processes that affect many organ systems in the body. Furthermore, it is becoming more apparent that the connection between gut dysbiosis and age-related diseases may lie in how the gut microbiome communicates with both the intestinal mucosa and the systemic immune system, given that these networks have a common interconnection to frailty. We therefore discuss recent advances in our understanding of the important role the microbiome plays in aging and how this knowledge opens the door for potential novel therapeutics aimed at shaping a less dysbiotic microbiome to prevent or treat age-related diseases.
Collapse
Affiliation(s)
- John P Haran
- Department of Emergency Medicine; Department of Microbiology and Physiological Systems; Center for Microbiome Research, University of Massachusetts Medical School, Worcester, Massachusetts.
| | - Beth A McCormick
- Department of Microbiology and Physiological Systems; Center for Microbiome Research, University of Massachusetts Medical School, Worcester, Massachusetts
| |
Collapse
|
|
44
|
Goldansaz SA, Markus S, Berjanskii M, Rout M, Guo AC, Wang Z, Plastow G, Wishart DS. Candidate serum metabolite biomarkers of residual feed intake and carcass merit in sheep. J Anim Sci 2020; 98:5905257. [PMID: 32926096 DOI: 10.1093/jas/skaa298] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 09/11/2020] [Indexed: 12/15/2022] Open
Abstract
Mutton and lamb sales continue to grow globally at a rate of 5% per year. However, sheep farming struggles with low profit margins due to high feed costs and modest carcass yields. Selecting those sheep expected to convert feed efficiently and have high carcass merit, as early as possible in their life cycle, could significantly improve the profitability of sheep farming. Unfortunately, direct measurement of feed conversion efficiency (via residual feed intake [RFI]) and carcass merit is a labor-intensive and expensive procedure. Thus, indirect, marker-assisted evaluation of these traits has been explored as a means of reducing the cost of its direct measurement. One promising and potentially inexpensive route to discover biomarkers of RFI and/or carcass merit is metabolomics. Using quantitative metabolomics, we profiled the blood serum metabolome (i.e., the sum of all measurable metabolites) associated with sheep RFI and carcass merit and identified candidate biomarkers of these traits. The study included 165 crossbred ram-lambs that underwent direct measurement of feed consumption to determine their RFI classification (i.e., low vs. high) using the GrowSafe System over a period 40 d. Carcass merit was evaluated after slaughter using standardized methods. Prior to being sent to slaughter, one blood sample was drawn from each animal, and serum prepared and frozen at -80 °C to limit metabolite degradation. A subset of the serum samples was selected based on divergent RFI and carcass quality for further metabolomic analyses. The analyses were conducted using three analytical methods (nuclear magnetic resonance spectroscopy, liquid chromatography mass spectrometry, and inductively coupled mass spectrometry), which permitted the identification and quantification of 161 unique metabolites. Biomarker analyses identified three significant (P < 0.05) candidate biomarkers of sheep RFI (AUC = 0.80), seven candidate biomarkers of carcass yield grade (AUC = 0.77), and one candidate biomarker of carcass muscle-to-bone ratio (AUC = 0.74). The identified biomarkers appear to have roles in regulating energy metabolism and protein synthesis. These results suggest that serum metabolites could be used to categorize and predict sheep for their RFI and carcass merit. Further validation using a larger (3×) and more diverse cohort of sheep is required to confirm these findings.
Collapse
Affiliation(s)
- Seyed Ali Goldansaz
- Department of Agriculture, Food and Nutritional Sciences, University of Alberta, Edmonton, Canada.,Department of Biological Sciences, University of Alberta, Edmonton, Canada
| | - Susan Markus
- Alberta Agriculture and Forestry, Stettler, Canada
| | - Mark Berjanskii
- Department of Biological Sciences, University of Alberta, Edmonton, Canada
| | - Manoj Rout
- Department of Biological Sciences, University of Alberta, Edmonton, Canada
| | - An Chi Guo
- Department of Biological Sciences, University of Alberta, Edmonton, Canada
| | - Zhiquan Wang
- Department of Agriculture, Food and Nutritional Sciences, University of Alberta, Edmonton, Canada
| | - Graham Plastow
- Department of Agriculture, Food and Nutritional Sciences, University of Alberta, Edmonton, Canada
| | - David S Wishart
- Department of Biological Sciences, University of Alberta, Edmonton, Canada.,Department of Computing Science, University of Alberta, Edmonton, Canada
| |
Collapse
|
|
45
|
Harville EW, Bazzano L, Qi L, He J, Dorans K, Perng W, Kelly T. Branched-chain amino acids, history of gestational diabetes, and breastfeeding: The Bogalusa Heart Study. Nutr Metab Cardiovasc Dis 2020; 30:2077-2084. [PMID: 32819784 PMCID: PMC7606618 DOI: 10.1016/j.numecd.2020.06.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 06/17/2020] [Accepted: 06/18/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND AND AIMS To examine the associations between history of gestational diabetes mellitus (GDM) and breastfeeding with branched-chain amino acids (BCAA) and their metabolites in later life. METHODS AND RESULTS 638 women (mean age 48.0 y) who had participated in the Bogalusa Heart Study and substudies of pregnancy history had untargeted, ultrahigh performance liquid chromatography-tandem mass spectroscopy conducted by Metabolon© on serum samples. Metabolites were identified that were BCAA or associated with BCAA metabolic pathways. History of GDM at any pregnancy (self-reported, confirmed with medical records when possible) as well as breastfeeding were examined as predictors of BCAA using linear models, controlling for age, race, BMI, waist circumference, and menopausal status. None of the BCAA differed statistically by history of either GDM or breastfeeding, although absolute levels of each of the BCAA were higher with GDM and lower with breastfeeding. Of the 27 metabolites on the leucine, isoleucine and valine metabolism subpathway, 1-carboxyethylleucine, 1-carboxyethyvaline, and 3-hydroxy-2-ethylpropionate were higher in women with a history of GDM, but lower in women in women with a history of breastfeeding. Similar results were found for alpha-hydroxyisocaproate, 1-carboxyethylisoleucine, and N-acetylleucine. CONCLUSIONS GDM and breastfeeding are associated in opposite directions with several metabolites on the BCAA metabolic pathway.
Collapse
Affiliation(s)
- Emily W Harville
- Department of Epidemiology, Tulane School of Public Health and Tropical Medicine, New Orleans, LA, United States.
| | - Lydia Bazzano
- Department of Epidemiology, Tulane School of Public Health and Tropical Medicine, New Orleans, LA, United States
| | - Lu Qi
- Department of Epidemiology, Tulane School of Public Health and Tropical Medicine, New Orleans, LA, United States
| | - Jiang He
- Department of Epidemiology, Tulane School of Public Health and Tropical Medicine, New Orleans, LA, United States
| | - Kirsten Dorans
- Department of Epidemiology, Tulane School of Public Health and Tropical Medicine, New Orleans, LA, United States
| | - Wei Perng
- Department of Epidemiology, Colorado School of Public Health, Denver, CO, United States
| | - Tanika Kelly
- Department of Epidemiology, Tulane School of Public Health and Tropical Medicine, New Orleans, LA, United States
| |
Collapse
|
|
46
|
Zhu B, Zhai Y, Ji M, Wei Y, Wu J, Xue W, Tao WW, Wu H. Alisma orientalis Beverage Treats Atherosclerosis by Regulating Gut Microbiota in ApoE -/- Mice. Front Pharmacol 2020; 11:570555. [PMID: 33101028 PMCID: PMC7545905 DOI: 10.3389/fphar.2020.570555] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Accepted: 09/07/2020] [Indexed: 12/11/2022] Open
Abstract
Background Alisma orientalis beverage (AOB) is a Chinese traditional medicine formulated with a diversity of medicinal plants and used for treating metabolic syndrome and atherosclerosis (AS) since time ago. Given the current limited biological research on AOB, the mechanism by which AOB treats AS is unknown. This study investigats the role of AOB-induced gut microbiota regulation in the expansion of AS. Methods We established an AS model in male apolipoprotein E-deficient (ApoE−/−) mice that are fed with a high-fat diet (HFD), treated with numerous interventions, and evaluated the inflammatory cytokines and serum biochemical indices. The root of the aorta was stained with oil red O, and the proportion of the lesion area was quantified. Trimethylamine N-oxide (TMAO) and trimethylamine (TMA) levels in serum were evaluated through liquid chromatography with mass spectrometry. Flavin−containing monooxygenase 3 (FMO3) liver protein expression was assessed by Western blotting. 16S rDNA sequencing technique was adopted to establish the changes in the microbiota structure. Results After 8 weeks of HFD feeding, an inflammatory cytokine, and AS development expression were significantly decreased in mice treated with AOB; the same parameters in the mice treated with the antibiotics cocktail did not change. In the gut microbiota study, mice treated with AOB had a markedly different gut microbiota than the HFD-fed mice. Additionally, AOB also decreased serum TMAO and hepatic FMO3 expression. Conclusion The antiatherosclerotic effects of AOB were found associated with changes in the content of gut microbiota and a reduction in TMAO, a gut microbiota metabolite, suggesting that AOB has potential therapeutic value in the treatment of AS.
Collapse
Affiliation(s)
- Boran Zhu
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yi Zhai
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Mengjiao Ji
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yanan Wei
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jiafei Wu
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Wenda Xue
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Wei Wei Tao
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Haoxin Wu
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| |
Collapse
|
|
47
|
Moran-Ramos S, Lopez-Contreras BE, Villarruel-Vazquez R, Ocampo-Medina E, Macias-Kauffer L, Martinez-Medina JN, Villamil-Ramirez H, León-Mimila P, Del Rio-Navarro BE, Ibarra-Gonzalez I, Vela-Amieva M, Gomez-Perez FJ, Velazquez-Cruz R, Salmeron J, Reyes-Castillo Z, Aguilar-Salinas C, Canizales-Quinteros S. Environmental and intrinsic factors shaping gut microbiota composition and diversity and its relation to metabolic health in children and early adolescents: A population-based study. Gut Microbes 2020; 11:900-917. [PMID: 31973685 PMCID: PMC7524342 DOI: 10.1080/19490976.2020.1712985] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Gut microbiota, by influencing multiple metabolic processes in the host, is an important determinant of human health and disease. However, gut dysbiosis associated with metabolic complications shows inconsistent patterns. This is likely driven by factors shaping gut microbial composition that have largely been under-evaluated, at a population level, in school-age children, especially from developing countries. RESULTS Through characterization, by 16S sequencing, of the largest gut microbial population-based school-aged children cohort in Latin America (ORSMEC, N = 926, aged 6-12 y), we identified associations of 14 clinical and environmental covariates (PFDR<0.1), collectively explaining 15.7% of the inter-individual gut microbial variation. Extrinsic factors such as markers of socioeconomic status showed a major influence in the most abundant taxa and in the enterotypes' distribution. Age was positively correlated with higher diversity, but only in normal-weight children (rho = 0.138, P =2 × 10-3). In contrast, this correlation although not significant, was negative in overweight and obese children (rho = -0.125, P = 0.104 and rho = -0.058, P = 0.409, respectively). Finally, co-abundance groups (CAGs) were associated with the presence of metabolic complications. CONCLUSIONS Our study offers evidence that the presence of overweight and obesity could impair the microbial diversity maturation associated with age. Furthermore, it provides novel results toward a better understanding of gut microbiota in the pediatric population that will ultimately help to develop therapeutic approaches to improve metabolic status.
Collapse
Affiliation(s)
- Sofia Moran-Ramos
- Catedratica, Consejo Nacional De Ciencia Y Tecnología (CONACYT), Mexico City, México,Unidad De Genómica De Poblaciones Aplicada a La Salud, Facultad De Química, UNAM/Instituto Nacional De Medicina Genómica (INMEGEN), Mexico City, México
| | - Blanca E. Lopez-Contreras
- Unidad De Genómica De Poblaciones Aplicada a La Salud, Facultad De Química, UNAM/Instituto Nacional De Medicina Genómica (INMEGEN), Mexico City, México
| | - Ricardo Villarruel-Vazquez
- Unidad De Genómica De Poblaciones Aplicada a La Salud, Facultad De Química, UNAM/Instituto Nacional De Medicina Genómica (INMEGEN), Mexico City, México
| | - Elvira Ocampo-Medina
- Unidad De Genómica De Poblaciones Aplicada a La Salud, Facultad De Química, UNAM/Instituto Nacional De Medicina Genómica (INMEGEN), Mexico City, México
| | - Luis Macias-Kauffer
- Unidad De Genómica De Poblaciones Aplicada a La Salud, Facultad De Química, UNAM/Instituto Nacional De Medicina Genómica (INMEGEN), Mexico City, México
| | - Jennifer N. Martinez-Medina
- Unidad De Genómica De Poblaciones Aplicada a La Salud, Facultad De Química, UNAM/Instituto Nacional De Medicina Genómica (INMEGEN), Mexico City, México
| | - Hugo Villamil-Ramirez
- Unidad De Genómica De Poblaciones Aplicada a La Salud, Facultad De Química, UNAM/Instituto Nacional De Medicina Genómica (INMEGEN), Mexico City, México
| | - Paola León-Mimila
- Unidad De Genómica De Poblaciones Aplicada a La Salud, Facultad De Química, UNAM/Instituto Nacional De Medicina Genómica (INMEGEN), Mexico City, México
| | - Blanca E. Del Rio-Navarro
- Servicio de Alergia e Inmunologia Clinica, Hospital Infantil México Federico Gómez, Mexico City, México
| | - Isabel Ibarra-Gonzalez
- Instituto De Investigaciones Biomédicas, UNAM - Instituto Nacional De Pediatría, Mexico City, México
| | - Marcela Vela-Amieva
- Laboratorio De Errores Innatos Del Metabolismo Y Tamiz, Instituto Nacional De Pediatría, Mexico City, México
| | - Francisco J Gomez-Perez
- Departamento De Endocrinología Y Metabolismo, Instituto Nacional De Ciencias Médicas Y Nutrición Salvador Zubirán, Mexico City, México
| | | | - Jorge Salmeron
- Centro de Investigación en Políticas, Población y Salud de la Facultad de Medicina-UNAM, Mexico City, Mexico
| | - Zyanya Reyes-Castillo
- Instituto de Investigaciones en Comportamiento Alimentario y Nutricion (IICAN), Universidad de Guadalajara - Centro Universitario del Sur, Ciudad Guzman, Jalisco, Mexico
| | - Carlos Aguilar-Salinas
- Unidad De Investigación En Enfermedades Metabólicas and Departamento De Endocrinología Y Metabolismo, Instituto Nacional De Ciencias Médicas Y Nutrición Salvador Zubirán, Mexico City, Mexico,Tecnológico De Monterrey, Escuela De Medicina Y Ciencias De La Salud, Monterrey, México
| | - Samuel Canizales-Quinteros
- Unidad De Genómica De Poblaciones Aplicada a La Salud, Facultad De Química, UNAM/Instituto Nacional De Medicina Genómica (INMEGEN), Mexico City, México,CONTACT Samuel Canizales-Quinteros
| |
Collapse
|
|
48
|
Associations of types of dairy consumption with adiposity: cross-sectional findings from over 12 000 adults in the Fenland Study, UK. Br J Nutr 2020; 122:928-935. [PMID: 31342887 DOI: 10.1017/s0007114519001776] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Evidence from randomised controlled trials supports beneficial effects of total dairy products on body weight, fat and lean mass, but evidence on associations of dairy types with distributions of body fat and lean mass is limited. We aimed to investigate associations of total and different types of dairy products with markers of adiposity, and body fat and lean mass distribution. We evaluated cross-sectional data from 12 065 adults aged 30-65 years recruited to the Fenland Study between 2005 and 2015 in Cambridgeshire, UK. Diet was assessed with an FFQ. We estimated regression coefficients (or percentage differences) and their 95 % CI using multiple linear regression models. The medians of milk, yogurt and cheese consumption were 293 (interquartile range (IQR) 146-439), 35·3 (IQR 8·8-71·8) and 14·6 (IQR 4·8-26·9) g/d, respectively. Low-fat dairy consumption was inversely associated with visceral:subcutaneous fat ratio estimated with dual-energy X-ray absorptiometry (-2·58 % (95 % CI -3·91, -1·23 %) per serving/d). Habitual consumption per serving/d (200 g) of milk was associated with 0·33 (95 % CI 0·19, 0·46) kg higher lean mass. Other associations were not significant after false discovery correction. Our findings suggest that the influence of milk consumption on lean mass and of low-fat dairy consumption on fat mass distribution may be potential pathways for the link between dairy consumption and metabolic risk. Our cross-sectional findings warrant further research in prospective and experimental studies in diverse populations.
Collapse
|
|
49
|
Klancic T, Reimer RA. Gut microbiota and obesity: Impact of antibiotics and prebiotics and potential for musculoskeletal health. JOURNAL OF SPORT AND HEALTH SCIENCE 2020; 9:110-118. [PMID: 32099719 PMCID: PMC7031774 DOI: 10.1016/j.jshs.2019.04.004] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/08/2018] [Revised: 03/06/2019] [Accepted: 03/12/2019] [Indexed: 06/10/2023]
Abstract
Obesity is a complex disease with multiple contributing factors. One of the most intensely studied factors during the past decade has been the gut microbiota, which is the community of all microbes in the intestinal tract. The gut microbiota, via energy extraction, inflammation, and other actions, is now recognized as an important player in the pathogenesis of obesity. Dysbiosis, or an imbalance in the microbial community, can initiate a cascade of metabolic disturbances in the host. Early life is a particularly important period for the development of the gut microbiota, and perturbations such as with antibiotic exposure can have long-lasting consequences for host health. In early life and throughout the life span, diet is one of the most important factors that shape the gut microbiota. Although diets high in fat and sugar have been shown to contribute to dysbiosis and disease, dietary fiber is recognized as an important fermentative fuel for the gut microbiota and results in the production of short-chain fatty acids that can act as signaling molecules in the host. One particular type of fiber, prebiotic fiber, contributes to changes in the gut microbiota, the most notable of which is an increase in the abundance of Bifidobacterium. This review highlights our current understanding of the role of gut microbiota in obesity development and the ways in which manipulating the microbiota through dietary means, specifically prebiotics, could contribute to improved health in the host, including musculoskeletal health.
Collapse
Affiliation(s)
- Teja Klancic
- Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, Canada
| | - Raylene A Reimer
- Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, Canada; Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
| |
Collapse
|
|
50
|
Calcium Oxalate Nephrolithiasis and Gut Microbiota: Not just a Gut-Kidney Axis. A Nutritional Perspective. Nutrients 2020; 12:nu12020548. [PMID: 32093202 PMCID: PMC7071363 DOI: 10.3390/nu12020548] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 02/14/2020] [Accepted: 02/18/2020] [Indexed: 12/13/2022] Open
Abstract
Recent studies have shown that patients with kidney stone disease, and particularly calcium oxalate nephrolithiasis, exhibit dysbiosis in their fecal and urinary microbiota compared with controls. The alterations of microbiota go far beyond the simple presence and representation of Oxalobacter formigenes, a well-known symbiont exhibiting a marked capacity of degrading dietary oxalate and stimulating oxalate secretion by the gut mucosa. Thus, alterations of the intestinal microbiota may be involved in the pathophysiology of calcium kidney stones. However, the role of nutrition in this gut-kidney axis is still unknown, even if nutritional imbalances, such as poor hydration, high salt, and animal protein intake and reduced fruit and vegetable intake, are well-known risk factors for kidney stones. In this narrative review, we provide an overview of the gut-kidney axis in nephrolithiasis from a nutritional perspective, summarizing the evidence supporting the role of nutrition in the modulation of microbiota composition, and their relevance for the modulation of lithogenic risk.
Collapse
|