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Di W, Xue C, Lin Y, Zhang W, Zhou Y. Exosome miR-152-3p derived from small intestinal epithelium modulates aging process in adipocytes. 3 Biotech 2025; 15:163. [PMID: 40375937 PMCID: PMC12075044 DOI: 10.1007/s13205-025-04346-x] [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: 02/09/2025] [Accepted: 05/04/2025] [Indexed: 05/18/2025] Open
Abstract
Exosomes play a crucial role in facilitating intracellular communication between cells and tissues. The small intestine epithelium secretes exosomes, which is involved in various physiologic and pathologic processes. In this study, we investigated the effects of exosomal miR-152-3p derived from small intestinal epithelium on the aging process of adipocytes and its potential downstream mechanism. The exosomes derived from small intestinal epithelial cells were identified and characterized by TEM, NTA, and Western blot (WB). CCK-8 assay demonstrated the concentration-dependently increased 3T3-L1 cell viability by exosomes. PCR, Mito-Tracker red and DCFH-DA staining demonstrated the increased mtDNA content, mitochondrial activity, and the declined ROS content in 3T3-L1 adipocytes co-cultured with young exosomes. WB, PCR, β-galactosidase staining and ELISA demonstrated that the senescence was suppressed, uncoupling protein 1 (UCP1) and PPARgamma coactivator 1-alpha (PGC-1α) expression were upregulated, the levels of proinflammatory tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) were decreased in 3T3-L1 adipocytes co-cultured with young exosomes. Luciferase reporter assay determined the binding between miR-152-3p and PGC-1α. WB and PCR manifested that miR-152-3p was lowly expressed in young exosomes and miR-152-3p could decrease PGC-1α expression and increase the expression of senescence-related genes. Moreover, ITT and GTT and H&E staining in in vivo elderly mouse model demonstrated that miR-152-3p inhibitor decreased visceral fat, improved glucose tolerance and insulin sensitivity and inhibited aging. WB and PCR suggested that miR-152-3p inhibitor enhanced PGC-1α expression, suppressed the expression of senescence-related genes and proinflammatory factors in vivo. In summary, intestinal exosomes affect the browning function of adipocytes through miR-152-3p, modulating the aging process.
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Affiliation(s)
- Wenjuan Di
- Department of Geriatrics, Division of Geriatric Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029 China
| | - Cheng Xue
- Department of Geriatrics, Division of Geriatric Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029 China
| | - Yunyun Lin
- Department of Geriatrics, Division of Geriatric Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029 China
| | - Wenling Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029 Jiangsu China
| | - Yichan Zhou
- Department of Geriatrics, Division of Geriatric Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029 China
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2
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Caesar R. The impact of novel probiotics isolated from the human gut on the gut microbiota and health. Diabetes Obes Metab 2025; 27 Suppl 1:3-14. [PMID: 39726216 PMCID: PMC11894790 DOI: 10.1111/dom.16129] [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: 10/25/2024] [Revised: 12/02/2024] [Accepted: 12/02/2024] [Indexed: 12/28/2024]
Abstract
The gut microbiota plays a pivotal role in influencing the metabolism and immune responses of the body. A balanced microbial composition promotes metabolic health through various mechanisms, including the production of beneficial metabolites, which help regulate inflammation and support immune functions. In contrast, imbalance in the gut microbiota, known as dysbiosis, can disrupt metabolic processes and increase the risk of developing diseases, such as obesity, type 2 diabetes, and inflammatory disorders. The composition of the gut microbiota is dynamic and can be influenced by environmental factors such as diet, medication, and the consumption of live bacteria. Since the early 1900s, bacteria isolated from food and have been used as probiotics. However, the human gut also offers an enormous reservoir of bacterial strains, and recent advances in microbiota research have led to the discovery of strains with probiotic potentials. These strains, derived from a broad spectrum of microbial taxa, differ in their ecological properties and how they interact with their hosts. For most probiotics bacterial structural components and metabolites, such as short-chain fatty acids, contribute to the maintenance of metabolic and immunological homeostasis by regulating inflammation and reinforcing gut barrier integrity. Metabolites produced by probiotic strains can also be used for bacterial cross-feeding to promote a balanced microbiota. Despite the challenges related to safety, stability, and strain-specific properties, several newly identified strains offer great potential for personalized probiotic interventions, allowing for targeted health strategies.
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Affiliation(s)
- Robert Caesar
- The Wallenberg Laboratory, Department of Molecular and Clinical MedicineUniversity of GothenburgGothenburgSweden
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Sirajee R, El Khatib S, Dieleman LA, Salla M, Baksh S. ImmunoMet Oncogenesis: A New Concept to Understand the Molecular Drivers of Cancer. J Clin Med 2025; 14:1620. [PMID: 40095546 PMCID: PMC11900543 DOI: 10.3390/jcm14051620] [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: 10/31/2024] [Revised: 02/10/2025] [Accepted: 02/25/2025] [Indexed: 03/19/2025] Open
Abstract
The appearance of cancer progresses through a multistep process that includes genetic, epigenetic, mutational, inflammatory and metabolic disturbances to signaling pathways within an organ. The combined influence of these changes will dictate the growth properties of the cells; the direction of further malignancy depends on the severity of these "disturbances". The molecular mechanisms driving abnormal inflammation and metabolism are beginning to be identified and, in some cases, are quite prominent in pre-condition states of cancer and are significant drivers of the malignant phenotype. As such, utilizing signaling pathways linked to inflammation and metabolism as biomarkers of cancer is an emerging method and includes pathways beyond those well characterized to drive metabolism or inflammation. In this review, we will discuss several emerging elements influencing proliferation, inflammation and metabolism that may play a part as drivers of the cancer phenotype. These include AMPK and leptin (linked to metabolism), NOD2/RIPK2, TAK1 (linked to inflammation), lactate and pyruvate transporters (monocarboxylate transporter [MCT], linked to mitochondrial biogenesis and metabolism) and RASSF1A (linked to proliferation, cell death, cell cycle control, inflammation and epigenetics). We speculate that the aforementioned elements are important drivers of carcinogenesis that should be collectively referenced as being involved in "ImmunoMET Oncogenesis", a new tripartite description of the role of elements in driving cancer. This term would suggest that for a better understanding of cancer, we need to understand how proliferation, inflammation and metabolic pathways are impacted and how they influence classical drivers of malignant transformation in order to drive ImmunoMET oncogenesis and the malignant state.
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Affiliation(s)
- Reshma Sirajee
- Faculty of Science, 1-001 CCIS, University of Alberta, Edmonton, AB T6G 2E1, Canada;
| | - Sami El Khatib
- Department of Biological & Chemical Sciences, Bekaa Campus, Lebanese International University, West Bekaa, Khiyara 1106, Lebanon; (S.E.K.); (M.S.)
- Center for Applied Mathematics and Bioinformatics (CAMB), Gulf University for Science and Technology, Kuwait City 32093, Kuwait
| | - Levinus A. Dieleman
- Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, 113 Street 87 Avenue, Edmonton, AB T6G 2E1, Canada;
| | - Mohamed Salla
- Department of Biological & Chemical Sciences, Bekaa Campus, Lebanese International University, West Bekaa, Khiyara 1106, Lebanon; (S.E.K.); (M.S.)
| | - Shairaz Baksh
- Department of Pediatrics, Biochemistry and Division of Experimental Oncology, Faculty of Medicine and Dentistry, University of Alberta, 113 Street 87 Avenue, Edmonton, AB T6G 2E1, Canada
- Women and Children’s Health Research Institute, Edmonton Clinic Health Academy (ECHA), University of Alberta, 4-081 11405 87 Avenue, Edmonton, AB T6G 1C9, Canada
- BioImmuno Designs, 4747 154 Avenue, Edmonton, AB T5Y 0C2, Canada
- Bio-Stream Diagnostics, 2011 94 Street, Edmonton, AB T6H 1N1, Canada
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4
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Xu Z, Chen M, Ng SC. Metabolic Regulation of Microbiota and Tissue Response. Gastroenterol Clin North Am 2024; 53:399-412. [PMID: 39068002 DOI: 10.1016/j.gtc.2024.01.003] [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] [Indexed: 07/30/2024]
Abstract
The microbiota in our gut regulates the sophisticated metabolic system that the human body has, essentially converting food into energy and the building blocks for various bodily functions. In this review, we discuss the multifaceted impact of the microbiota on host nutritional status by producing short-chain fatty acids, influencing gut hormones and mediating bile acid metabolism, and the key role in maintaining intestinal barrier integrity and immune homeostasis. Understanding and leveraging the power of the gut microbiome holds tremendous potential for enhancing human health and preventing various diseases.
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Affiliation(s)
- Zhilu Xu
- Microbiota I-Center (MagIC), Hong Kong SAR, China; Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Manman Chen
- Microbiota I-Center (MagIC), Hong Kong SAR, China; Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Siew Chien Ng
- Microbiota I-Center (MagIC), Hong Kong SAR, China; Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.
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Jamka JR, Gulbransen BD. Mechanisms of enteric neuropathy in diverse contexts of gastrointestinal dysfunction. Neurogastroenterol Motil 2024:e14870. [PMID: 39038157 DOI: 10.1111/nmo.14870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 06/11/2024] [Accepted: 07/10/2024] [Indexed: 07/24/2024]
Abstract
The enteric nervous system (ENS) commands moment-to-moment gut functions through integrative neurocircuitry housed in the gut wall. The functional continuity of ENS networks is disrupted in enteric neuropathies and contributes to major disturbances in normal gut activities including abnormal gut motility, secretions, pain, immune dysregulation, and disrupted signaling along the gut-brain axis. The conditions under which enteric neuropathy occurs are diverse and the mechanistic underpinnings are incompletely understood. The purpose of this brief review is to summarize the current understanding of the cell types involved, the conditions in which neuropathy occurs, and the mechanisms implicated in enteric neuropathy such as oxidative stress, toll like receptor signaling, purines, and pre-programmed cell death.
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Affiliation(s)
- Julia R Jamka
- Department of Physiology, Michigan State University, East Lansing, Michigan, USA
| | - Brian D Gulbransen
- Department of Physiology, Michigan State University, East Lansing, Michigan, USA
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Liu Y, Chen H, Yan X, Zhang J, Deng Z, Huang M, Gu J, Zhang J. MyD88 in myofibroblasts enhances nonalcoholic fatty liver disease-related hepatocarcinogenesis via promoting macrophage M2 polarization. Cell Commun Signal 2024; 22:86. [PMID: 38291436 PMCID: PMC10826060 DOI: 10.1186/s12964-024-01489-x] [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: 10/09/2023] [Accepted: 01/11/2024] [Indexed: 02/01/2024] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver diseases and has emerged as the leading factor in the pathogenesis of hepatocellular carcinoma (HCC). MyD88 contributes to the development of HCC. However, the underlying mechanism by which MyD88 in myofibroblasts regulates NAFLD-associated liver cancer development remains unknown. RESULTS Myofibroblast MyD88-deficient (SMAMyD88-/-) mice were protected from diet-induced obesity and developed fewer and smaller liver tumors. MyD88 deficiency in myofibroblasts attenuated macrophage M2 polarization and fat accumulation in HCC tissues. Mechanistically, MyD88 signaling in myofibroblasts enhanced CCL9 secretion, thereby promoting macrophage M2 polarization. This process may depend on the CCR1 receptor and STAT6/ PPARβ pathway. Furthermore, liver tumor growth was attenuated in mice treated with a CCR1 inhibitor. CCLl5 (homologous protein CCL9 in humans) expression was increased in myofibroblasts of HCC and was associated with shorter survival of patients with HCC. Thus, our results indicate that MyD88 in myofibroblasts promotes NAFLD-related HCC progression and may be a promising therapeutic target for HCC treatment. CONCLUSION This study demonstrates that MyD88 in myofibroblasts can promote nonalcoholic fatty liver disease-related hepatocarcinogenesis by enhancing macrophage M2 polarization, which might provide a potential molecular therapeutic target for HCC.
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Affiliation(s)
- Yu Liu
- College of Life Science and Bioengineering, Beijing Jiaotong University, No.3 Shangyuancun Road, Beijing, 100044, P.R. China
| | - Haiqiang Chen
- College of Life Science and Bioengineering, Beijing Jiaotong University, No.3 Shangyuancun Road, Beijing, 100044, P.R. China
| | - Xuanxuan Yan
- College of Life Science and Bioengineering, Beijing Jiaotong University, No.3 Shangyuancun Road, Beijing, 100044, P.R. China
| | - Jie Zhang
- College of Life Science and Bioengineering, Beijing Jiaotong University, No.3 Shangyuancun Road, Beijing, 100044, P.R. China
| | - Zhenzhong Deng
- Department of Oncology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, P. R. China
| | - Maosheng Huang
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jianchun Gu
- Department of Oncology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, P. R. China.
| | - Jinhua Zhang
- College of Life Science and Bioengineering, Beijing Jiaotong University, No.3 Shangyuancun Road, Beijing, 100044, P.R. China.
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Zhao Q, Wu J, Ding Y, Pang Y, Jiang C. Gut microbiota, immunity, and bile acid metabolism: decoding metabolic disease interactions. LIFE METABOLISM 2023; 2:load032. [PMID: 39872860 PMCID: PMC11749371 DOI: 10.1093/lifemeta/load032] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 07/14/2023] [Accepted: 07/21/2023] [Indexed: 01/03/2025]
Abstract
In recent decades, the global prevalence of metabolic syndrome has surged, posing a significant public health challenge. Metabolic disorders, encompassing diabetes, obesity, nonalcoholic fatty liver disease, and polycystic ovarian syndrome, have been linked to alterations in the gut microbiota. Nonetheless, the connection between gut microbiota and host metabolic diseases warrants further investigation. In this review, we delve into the associations between various metabolic disorders and the gut microbiota, focusing on immune responses and bile acid (BA) metabolism. Notably, T helper cells, innate lymphoid cells, macrophages, and dendritic cells have been shown to modulate host metabolism through interactions with intestinal microorganisms and the release of cytokines. Furthermore, secondary BA metabolites, derived from the microbiota, are involved in the pathogenesis of metabolic diseases via the farnesoid X receptor and Takeda G protein-coupled receptor 5. By covering both aspects of this immune system-microorganism axis, we present a comprehensive overview of the roles played by the gut microbiota, microbiota-derived BA metabolites, and immune responses in metabolic diseases, as well as the interplay between these systems.
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Affiliation(s)
- Qixiang Zhao
- Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China
- Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, Peking University, Beijing 100191, China
| | - Jiayu Wu
- Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China
- Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, Peking University, Beijing 100191, China
| | - Yong Ding
- Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China
- Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, Peking University, Beijing 100191, China
| | - Yanli Pang
- Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China
| | - Changtao Jiang
- Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China
- Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, Peking University, Beijing 100191, China
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Liu Z, Sun H, Xu S, Wang H, Zhang Z, Wei Y, Kou Y, Wang Y. Dietary ingredient change induces a transient MyD88-dependent mucosal enteric glial cell response and promotes obesity. Nutr Neurosci 2023; 26:1183-1193. [PMID: 36342063 DOI: 10.1080/1028415x.2022.2142129] [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] [Indexed: 11/09/2022]
Abstract
OBJECTIVE Consumption of a modern Western-type high-fat low-fiber diet increases the risk of obesity. However, how a host responds to such a diet, especially during the early period of dietary transition from a previous low-fat and fiber-rich diet, remains poorly explored. METHODS Wild-type C57BL/6 mice were fed a normal chow diet or a high-fat diet. Enteric glial cell (EGC) activation was detected through quantitative real-time PCR (qRT-PCR), immunoblotting and immunohistology analysis. Fluorocitrate or genetic deletion of glial fibrillary acidic protein (GFAP)-positive glial-intrinsic myeloid differentiation factor 88 (Myd88) was used to inhibit EGC activation, and the effect of a high-fat diet on obesity was further investigated. The role of MYD88-dependent sensing of commensal products in adipocyte was observed to analyze the effect of obesity. RESULTS A dietary shift from a normal chow diet to a high-fat diet in mice induced a transient early-phase emergence of a GFAP-positive EGC network in the lamina propria of the ileum, accompanied with an increase in glial-derived neurotrophic factor production. Inhibition of glial cell activity blocked this response. GFAP-positive glial Myd88 knockout mice gained less body weight after high-fat diet (HFD) feeding than littermate controls. In contrast, adipocyte deletion of Myd88 in mice had no effect on weight gain but instead exacerbated glucose intolerance. Furthermore, short-term fluorocitrate intervention during HFD feeding attenuated body weight gain. CONCLUSIONS Our findings indicate that EGCs are early responders to intestinal ecosystem changes and the GFAP-positive glial Myd88 signaling participates in regulating obesity.
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Affiliation(s)
- Zhuanzhuan Liu
- Laboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, People's Republic of China
| | - Hongxiang Sun
- Laboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, People's Republic of China
| | - Shihong Xu
- Laboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, People's Republic of China
| | - Hanying Wang
- Laboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, People's Republic of China
| | - Zhiwei Zhang
- Laboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, People's Republic of China
| | - Yanxia Wei
- Laboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, People's Republic of China
| | - Yanbo Kou
- Laboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, People's Republic of China
| | - Yugang Wang
- Laboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, People's Republic of China
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9
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Shelton CD, Sing E, Mo J, Shealy NG, Yoo W, Thomas J, Fitz GN, Castro PR, Hickman TT, Torres TP, Foegeding NJ, Zieba JK, Calcutt MW, Codreanu SG, Sherrod SD, McLean JA, Peck SH, Yang F, Markham NO, Liu M, Byndloss MX. An early-life microbiota metabolite protects against obesity by regulating intestinal lipid metabolism. Cell Host Microbe 2023; 31:1604-1619.e10. [PMID: 37794592 PMCID: PMC10593428 DOI: 10.1016/j.chom.2023.09.002] [Citation(s) in RCA: 46] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 08/07/2023] [Accepted: 09/06/2023] [Indexed: 10/06/2023]
Abstract
The mechanisms by which the early-life microbiota protects against environmental factors that promote childhood obesity remain largely unknown. Using a mouse model in which young mice are simultaneously exposed to antibiotics and a high-fat (HF) diet, we show that Lactobacillus species, predominant members of the small intestine (SI) microbiota, regulate intestinal epithelial cells (IECs) to limit diet-induced obesity during early life. A Lactobacillus-derived metabolite, phenyllactic acid (PLA), protects against metabolic dysfunction caused by early-life exposure to antibiotics and a HF diet by increasing the abundance of peroxisome proliferator-activated receptor γ (PPAR-γ) in SI IECs. Therefore, PLA is a microbiota-derived metabolite that activates protective pathways in the small intestinal epithelium to regulate intestinal lipid metabolism and prevent antibiotic-associated obesity during early life.
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Affiliation(s)
- Catherine D Shelton
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Elizabeth Sing
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Jessica Mo
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Nicolas G Shealy
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Woongjae Yoo
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea
| | - Julia Thomas
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Gillian N Fitz
- Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
| | - Pollyana R Castro
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo 12083-862, Brazil
| | - Tara T Hickman
- Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
| | - Teresa P Torres
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Nora J Foegeding
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Jacob K Zieba
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - M Wade Calcutt
- Mass Spectrometry Research Center and Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
| | - Simona G Codreanu
- Center for Innovative Technology and Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA
| | - Stacy D Sherrod
- Center for Innovative Technology and Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA
| | - John A McLean
- Center for Innovative Technology and Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA
| | - Sun H Peck
- Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Biomedical Engineering, Vanderbilt University School of Engineering, Nashville, TN 37232, USA; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Fan Yang
- Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Nicholas O Markham
- Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Institute of Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Min Liu
- Department of Pathology and Molecular Medicine, Metabolic Diseases Institute, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA
| | - Mariana X Byndloss
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute of Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Digestive Disease Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Microbiome Innovation Center, Vanderbilt University, Nashville, TN 37235, USA; Howard Hughes Medical Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
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10
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Di Ciaula A, Bonfrate L, Khalil M, Garruti G, Portincasa P. Contribution of the microbiome for better phenotyping of people living with obesity. Rev Endocr Metab Disord 2023; 24:839-870. [PMID: 37119391 PMCID: PMC10148591 DOI: 10.1007/s11154-023-09798-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/10/2023] [Indexed: 05/01/2023]
Abstract
Obesity has reached epidemic proportion worldwide and in all ages. Available evidence points to a multifactorial pathogenesis involving gene predisposition and environmental factors. Gut microbiota plays a critical role as a major interface between external factors, i.e., diet, lifestyle, toxic chemicals, and internal mechanisms regulating energy and metabolic homeostasis, fat production and storage. A shift in microbiota composition is linked with overweight and obesity, with pathogenic mechanisms involving bacterial products and metabolites (mainly endocannabinoid-related mediators, short-chain fatty acids, bile acids, catabolites of tryptophan, lipopolysaccharides) and subsequent alterations in gut barrier, altered metabolic homeostasis, insulin resistance and chronic, low-grade inflammation. Although animal studies point to the links between an "obesogenic" microbiota and the development of different obesity phenotypes, the translational value of these results in humans is still limited by the heterogeneity among studies, the high variation of gut microbiota over time and the lack of robust longitudinal studies adequately considering inter-individual confounders. Nevertheless, available evidence underscores the existence of several genera predisposing to obesity or, conversely, to lean and metabolically health phenotype (e.g., Akkermansia muciniphila, species from genera Faecalibacterium, Alistipes, Roseburia). Further longitudinal studies using metagenomics, transcriptomics, proteomics, and metabolomics with exact characterization of confounders are needed in this field. Results must confirm that distinct genera and specific microbial-derived metabolites represent effective and precision interventions against overweight and obesity in the long-term.
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Affiliation(s)
- Agostino Di Ciaula
- Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari Medical School, 70124 Bari, Italy
| | - Leonilde Bonfrate
- Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari Medical School, 70124 Bari, Italy
| | - Mohamad Khalil
- Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari Medical School, 70124 Bari, Italy
| | - Gabriella Garruti
- Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari Medical School, 70124 Bari, Italy
| | - Piero Portincasa
- Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari Medical School, 70124 Bari, Italy
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11
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Yang M, Wang JH, Shin JH, Lee D, Lee SN, Seo JG, Shin JH, Nam YD, Kim H, Sun X. Pharmaceutical efficacy of novel human-origin Faecalibacterium prausnitzii strains on high-fat-diet-induced obesity and associated metabolic disorders in mice. Front Endocrinol (Lausanne) 2023; 14:1220044. [PMID: 37711887 PMCID: PMC10497875 DOI: 10.3389/fendo.2023.1220044] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 08/04/2023] [Indexed: 09/16/2023] Open
Abstract
INTRODUCTION Obesity and related metabolic issues are a growing global health concern. Recently, the discovery of new probiotics with anti-obesity properties has gained interest. METHODS In this study, four Faecalibacte-rium prausnitzii strains were isolated from healthy human feces and evaluated on a high-fat diet-induced mouse model for 12 weeks. RESULTS The F. prausnitzii strains reduced body weight gain, liver and fat weights, and calorie intake while improving lipid and glucose metabolism in the liver and adipose tissue, as evidenced by regulating lipid metabolism-associated gene expression, including ACC1, FAS, SREBP1c, leptin, and adiponectin. Moreover, the F. prausnitzii strains inhibited low-grade inflammation, restored gut integrity, and ameliorated hepatic function and insulin resistance. Interestingly, the F. prausnitzii strains modulated gut and neural hormone secretion and reduced appetite by affecting the gut-brain axis. Supplementation with F. prausnitzii strains noticeably changed the gut microbiota composition. DISCUSSION In summary, the novel isolated F. prausnitzii strains have therapeutic effects on obesity and associated metabolic disorders through modulation of the gut-brain axis. Additionally, the effectiveness of different strains might not be achieved through identical mechanisms. Therefore, the present findings provide a reliable clue for developing novel therapeutic probiotics against obesity and associated metabolic disorders.
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Affiliation(s)
- Meng Yang
- Department of Nephrology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
- Department of Rehabilitation Medicine of Korean Medicine, Dongguk University, Goyang-si, Republic of Korea
| | - Jing-Hua Wang
- Institute of Bioscience & Integrative Medicine, Daejeon University, Daejeon, Republic of Korea
| | - Joo-Hyun Shin
- R&D Center, Enterobiome Inc., Goyang-si, Republic of Korea
| | - Dokyung Lee
- R&D Center, Enterobiome Inc., Goyang-si, Republic of Korea
| | - Sang-Nam Lee
- R&D Center, Enterobiome Inc., Goyang-si, Republic of Korea
| | - Jae-Gu Seo
- R&D Center, Enterobiome Inc., Goyang-si, Republic of Korea
| | - Ji-Hee Shin
- Research Group of Healthcare, Korea Food Research Institute, Wanju-gun, Republic of Korea
| | - Young-Do Nam
- Research Group of Healthcare, Korea Food Research Institute, Wanju-gun, Republic of Korea
| | - Hojun Kim
- Department of Rehabilitation Medicine of Korean Medicine, Dongguk University, Goyang-si, Republic of Korea
| | - Xiaomin Sun
- Department of Nephrology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
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12
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Jia S, Li X, Du Q. Host insulin resistance caused by Porphyromonas gingivalis-review of recent progresses. Front Cell Infect Microbiol 2023; 13:1209381. [PMID: 37520442 PMCID: PMC10373507 DOI: 10.3389/fcimb.2023.1209381] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 06/27/2023] [Indexed: 08/01/2023] Open
Abstract
Porphyromonas gingivalis (P. gingivalis) is a Gram-negative oral anaerobic bacterium that plays a key role in the pathogenesis of periodontitis. P. gingivalis expresses a variety of virulence factors that disrupt innate and adaptive immunity, allowing P. gingivalis to survive and multiply in the host and destroy periodontal tissue. In addition to periodontal disease, P.gingivalis is also associated with systemic diseases, of which insulin resistance is an important pathological basis. P. gingivalis causes a systemic inflammatory response, disrupts insulin signaling pathways, induces pancreatic β-cell hypofunction and reduced numbers, and causes decreased insulin sensitivity leading to insulin resistance (IR). In this paper, we systematically review the studies on the mechanism of insulin resistance induced by P. gingivalis, discuss the association between P. gingivalis and systemic diseases based on insulin resistance, and finally propose relevant therapeutic approaches. Overall, through a systematic review of the mechanisms related to systemic diseases caused by P. gingivalis through insulin resistance, we hope to provide new insights for future basic research and clinical interventions for related systemic diseases.
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Affiliation(s)
- Shuxian Jia
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China
- Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Xiaobing Li
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China
- Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Qin Du
- Department of Stomatology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
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13
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Haneishi Y, Furuya Y, Hasegawa M, Takemae H, Tanioka Y, Mizutani T, Rossi M, Miyamoto J. Polyunsaturated fatty acids-rich dietary lipid prevents high fat diet-induced obesity in mice. Sci Rep 2023; 13:5556. [PMID: 37019935 PMCID: PMC10076282 DOI: 10.1038/s41598-023-32851-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 04/03/2023] [Indexed: 04/07/2023] Open
Abstract
Diet is the primary factor affecting host nutrition and metabolism, with excess food intake, especially high-calorie diets, such as high-fat and high-sugar diets, causing an increased risk of obesity and related disorders. Obesity alters the gut microbial composition and reduces microbial diversity and causes changes in specific bacterial taxa. Dietary lipids can alter the gut microbial composition in obese mice. However, the regulation of gut microbiota and host energy homeostasis by different polyunsaturated fatty acids (PUFAs) in dietary lipids remains unknown. Here, we demonstrated that different PUFAs in dietary lipids improved host metabolism in high-fat diet (HFD)-induced obesity in mice. The intake of the different PUFA-enriched dietary lipids improved metabolism in HFD-induced obesity by regulating glucose tolerance and inhibiting colonic inflammation. Moreover, the gut microbial compositions were different among HFD and modified PUFA-enriched HFD-fed mice. Thus, we have identified a new mechanism underlying the function of different PUFAs in dietary lipids in regulating host energy homeostasis in obese conditions. Our findings shed light on the prevention and treatment of metabolic disorders by targeting the gut microbiota.
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Affiliation(s)
- Yuri Haneishi
- Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, 183-8509, Japan
| | - Yuma Furuya
- Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, 183-8509, Japan
| | - Mayu Hasegawa
- Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, 183-8509, Japan
| | - Hitoshi Takemae
- Center for Infectious Diseases Epidemiology and Prevention Research: CEPiR, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, 183-8509, Japan
| | - Yuri Tanioka
- Department of International Food and Agricultural Science, Faculty of International Food and Agricultural Studies, Tokyo University of Agriculture, Setagaya-ku, Tokyo, 156-8502, Japan
| | - Tetsuya Mizutani
- Center for Infectious Diseases Epidemiology and Prevention Research: CEPiR, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, 183-8509, Japan
| | - Mauro Rossi
- Institute of Food Sciences, CNR, via Roma 64, 83100, Avellino, Italy
| | - Junki Miyamoto
- Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, 183-8509, Japan.
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14
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Liu M, Shi W, Huang Y, Wu Y, Wu K. Intestinal flora: A new target for traditional Chinese medicine to improve lipid metabolism disorders. Front Pharmacol 2023; 14:1134430. [PMID: 36937840 PMCID: PMC10014879 DOI: 10.3389/fphar.2023.1134430] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 02/13/2023] [Indexed: 03/05/2023] Open
Abstract
Lipid metabolism disorders (LMD) can cause a series of metabolic diseases, including hyperlipidemia, obesity, non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (AS). Its development is caused by more pathogenic factors, among which intestinal flora dysbiosis is considered to be an important pathogenic mechanism of LMD. In recent years, the research on intestinal flora has made great progress, opening up new perspectives on the occurrence and therapeutic effects of diseases. With its complex composition and wide range of targets, traditional Chinese medicine (TCM) is widely used to prevent and treat LMD. This review takes intestinal flora as a target, elaborates on the scientific connotation of TCM in the treatment of LMD, updates the therapeutic thinking of LMD, and provides a reference for clinical diagnosis and treatment.
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Affiliation(s)
- Min Liu
- Department of Gynecology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Wei Shi
- Department of Gynecology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Yefang Huang
- Department of Gynecology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Yeke Wu
- Department of Stomatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Keming Wu
- Department of Gynecology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
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15
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Min S, Than N, Shin YC, Hu G, Shin W, Ambrosini YM, Kim HJ. Live probiotic bacteria administered in a pathomimetic Leaky Gut Chip ameliorate impaired epithelial barrier and mucosal inflammation. Sci Rep 2022; 12:22641. [PMID: 36587177 PMCID: PMC9805460 DOI: 10.1038/s41598-022-27300-w] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 12/29/2022] [Indexed: 01/01/2023] Open
Abstract
Here, we report a pathomimetic Leaky Gut Chip that recapitulates increased epithelial permeability and intestinal inflammation to assess probiotic intervention as live biotherapeutics. We leveraged a mechanodynamic human gut-on-a-chip (Gut Chip) that recreates three-dimensional epithelial layers in a controlled oxygen gradient and biomechanical cues, where the addition of a cocktail of pro-inflammatory cytokines, TNF-α and IL-1β, reproducibly induced impaired epithelial barrier followed by intestinal inflammation. This inflamed leaky epithelium was not recovered for up to 3 days, although the cytokine treatment ceased. However, when probiotic bacteria, either Lactobacillus rhamnosus GG or a multi-species mixture (VSL#3), were respectively administered on the leaky epithelium, bacterial cells colonized mucosal surface and significantly improved barrier function, enhanced the localization of tight junction proteins such as ZO-1 and occludin, and elevated mucus production. In addition, inflammatory markers, including p65, pSTAT3, and MYD88, that were highly expressed in the germ-free control were significantly reduced when probiotic bacteria were co-cultured in a Leaky Gut Chip. Probiotic treatment also significantly reduced the production of secretory pro-inflammatory cytokines. Hence, our pathomimetic Leaky Gut Chip may offer a translational strategy to dissect the therapeutic mechanism of live biotherapeutic products and validate their clinical potential by incorporating patient-derived organoids.
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Affiliation(s)
- Soyoun Min
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave., NE3, Cleveland, OH, 44195, USA
| | - Nam Than
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave., NE3, Cleveland, OH, 44195, USA
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA
| | - Yong Cheol Shin
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave., NE3, Cleveland, OH, 44195, USA
| | - Grace Hu
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA
| | - Woojung Shin
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
- Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
| | - Yoko M Ambrosini
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164, USA
| | - Hyun Jung Kim
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave., NE3, Cleveland, OH, 44195, USA.
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16
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Kim G, Yoon Y, Park JH, Park JW, Noh MG, Kim H, Park C, Kwon H, Park JH, Kim Y, Sohn J, Park S, Kim H, Im SK, Kim Y, Chung HY, Nam MH, Kwon JY, Kim IY, Kim YJ, Baek JH, Kim HS, Weinstock GM, Cho B, Lee C, Fang S, Park H, Seong JK. Bifidobacterial carbohydrate/nucleoside metabolism enhances oxidative phosphorylation in white adipose tissue to protect against diet-induced obesity. MICROBIOME 2022; 10:188. [PMID: 36333752 PMCID: PMC9635107 DOI: 10.1186/s40168-022-01374-0] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 09/18/2022] [Indexed: 05/15/2023]
Abstract
BACKGROUND Comparisons of the gut microbiome of lean and obese humans have revealed that obesity is associated with the gut microbiome plus changes in numerous environmental factors, including high-fat diet (HFD). Here, we report that two species of Bifidobacterium are crucial to controlling metabolic parameters in the Korean population. RESULTS Based on gut microbial analysis from 99 Korean individuals, we observed the abundance of Bifidobacterium longum and Bifidobacterium bifidum was markedly reduced in individuals with increased visceral adipose tissue (VAT), body mass index (BMI), blood triglyceride (TG), and fatty liver. Bacterial transcriptomic analysis revealed that carbohydrate/nucleoside metabolic processes of Bifidobacterium longum and Bifidobacterium bifidum were associated with protecting against diet-induced obesity. Oral treatment of specific commercial Bifidobacterium longum and Bifidobacterium bifidum enhanced bile acid signaling contributing to potentiate oxidative phosphorylation (OXPHOS) in adipose tissues, leading to reduction of body weight gain and improvement in hepatic steatosis and glucose homeostasis. Bifidobacterium longum or Bifidobacterium bifidum manipulated intestinal sterol biosynthetic processes to protect against diet-induced obesity in germ-free mice. CONCLUSIONS Our findings support the notion that treatment of carbohydrate/nucleoside metabolic processes-enriched Bifidobacterium longum and Bifidobacterium bifidum would be a novel therapeutic strategy for reprograming the host metabolic homeostasis to protect against metabolic syndromes, including diet-induced obesity. Video Abstract.
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Affiliation(s)
- Gihyeon Kim
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, Korea
- Genome and Company, Pangyo-ro 255, Bundang-gu, Seongnam, Korea
| | - Youngmin Yoon
- Division of Nephrology, Department of Medicine, Chosun University Hospital, Chosun University School of Medicine, Gwangju, Korea
| | - Jin Ho Park
- Department of Family Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Won Park
- Genome and Company, Pangyo-ro 255, Bundang-gu, Seongnam, Korea
| | - Myung-Guin Noh
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, Korea
| | - Hyun Kim
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, Korea
| | - Changho Park
- Genome and Company, Pangyo-ro 255, Bundang-gu, Seongnam, Korea
| | - Hyuktae Kwon
- Department of Family Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | | | - Yena Kim
- Genome and Company, Pangyo-ro 255, Bundang-gu, Seongnam, Korea
| | - Jinyoung Sohn
- Genome and Company, Pangyo-ro 255, Bundang-gu, Seongnam, Korea
| | - Shinyoung Park
- Genome and Company, Pangyo-ro 255, Bundang-gu, Seongnam, Korea
| | - Hyeonhui Kim
- Graduate school of Medical Science, Brain Korea 21 Project, Severance Biomedical Science Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sun-Kyoung Im
- Graduate school of Medical Science, Brain Korea 21 Project, Severance Biomedical Science Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Yeongmin Kim
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, Korea
| | - Ha Yung Chung
- Korea Basic Science Institute, Seoul Center, Seoul, South Korea
| | - Myung Hee Nam
- Korea Basic Science Institute, Seoul Center, Seoul, South Korea
| | - Jee Young Kwon
- The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, 06032, USA
| | - Il Yong Kim
- Laboratory of Developmental Biology and Genomics, BK21 Plus Program for Advanced Veterinary Science and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Korea
- Korea Mouse Phenotyping Center, Seoul National University, Seoul, Korea
| | - Yong Jae Kim
- Korea Mouse Phenotyping Center, Seoul National University, Seoul, Korea
| | - Ji Hyeon Baek
- Korea Mouse Phenotyping Center, Seoul National University, Seoul, Korea
| | - Hak Su Kim
- Korea Mouse Phenotyping Center, Seoul National University, Seoul, Korea
| | - George M Weinstock
- The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, 06032, USA
| | - Belong Cho
- Department of Family Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Charles Lee
- The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, 06032, USA
- Department of Life Science, Ewha Womans University, Seoul, 03760, Korea
- The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Sungsoon Fang
- Graduate school of Medical Science, Brain Korea 21 Project, Severance Biomedical Science Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
| | - Hansoo Park
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, Korea.
- Genome and Company, Pangyo-ro 255, Bundang-gu, Seongnam, Korea.
| | - Je Kyung Seong
- Laboratory of Developmental Biology and Genomics, BK21 Plus Program for Advanced Veterinary Science and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
- Korea Mouse Phenotyping Center, Seoul National University, Seoul, Korea.
- Interdisciplinary Program for Bioinformatics, Seoul National University, Seoul, Korea.
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Li Y, Huang X, Yang G, Xu K, Yin Y, Brecchia G, Yin J. CD36 favours fat sensing and transport to govern lipid metabolism. Prog Lipid Res 2022; 88:101193. [PMID: 36055468 DOI: 10.1016/j.plipres.2022.101193] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 06/26/2022] [Accepted: 08/26/2022] [Indexed: 11/24/2022]
Abstract
CD36, located on the cell membrane, transports fatty acids in response to dietary fat. It is a critical fatty acid sensor and regulator of lipid metabolism. The interaction between CD36 and lipid dysmetabolism and obesity has been identified in various models and human studies. Nevertheless, the mechanisms by which CD36 regulates lipid metabolism and the role of CD36 in metabolic diseases remain obscure. Here, we summarize the latest research on the role of membrane CD36 in fat metabolism, with emphasis on CD36-mediated fat sensing and transport. This review also critically discusses the factors affecting the regulation of CD36-mediated fat dysfunction. Finally, we review previous clinical evidence of CD36 in metabolic diseases and consider the path forward.
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Affiliation(s)
- Yunxia Li
- College of Animal Science and Technology, Hunan Agriculture University, Changsha 410128, China
| | - Xingguo Huang
- College of Animal Science and Technology, Hunan Agriculture University, Changsha 410128, China
| | - Guan Yang
- Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong SAR, China
| | - Kang Xu
- Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China.
| | - Yulong Yin
- College of Animal Science and Technology, Hunan Agriculture University, Changsha 410128, China
| | - Gabriele Brecchia
- Department of Veterinary Medicine, University of Milano, Via dell'Università, 26900 Lodi, Italy
| | - Jie Yin
- College of Animal Science and Technology, Hunan Agriculture University, Changsha 410128, China.
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18
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Tirelle P, Salaün C, Kauffmann A, Bôle-Feysot C, Guérin C, Huré M, Goichon A, Amamou A, Breton J, do Rego JL, Déchelotte P, Achamrah N, Coëffier M. Intestinal Epithelial Toll-like Receptor 4 Deficiency Modifies the Response to the Activity-Based Anorexia Model in a Sex-Dependent Manner: A Preliminary Study. Nutrients 2022; 14:nu14173607. [PMID: 36079861 PMCID: PMC9460860 DOI: 10.3390/nu14173607] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 08/24/2022] [Accepted: 08/28/2022] [Indexed: 11/21/2022] Open
Abstract
The role of microbiota in eating disorders has recently emerged. Previous data reported that lipopolysaccharides induce anorexia and a decrease of body weight through the activation of toll-like receptor 4 (TLR4). In the activity-based anorexia (ABA) mouse model, an increase of TLR4 expression in intestinal epithelial cells (IEC) has been described. We thus aimed to characterize the role of TLR4 in IEC in the ABA model in male and female mice. For this purpose, Vill-CreERT2-TLR4 LoxP, which are depleted for TLR4 in IEC in response to 4-OH tamoxifen, were submitted (ABA) or not (CT) to the ABA procedure that combined free access to a running wheel and progressive time-limited access to food. We thus compared CT and ABA TLR4IEC−/− mice to CT and ABA TLR4IEC+/+ mice. In response to the ABA model, TLR4IEC+/+ male and female mice exhibited a body weight loss associated to a decrease of lean mass. In TLR4IEC−/− male mice, body weight loss was delayed and less pronounced compared to TLR4IEC+/+ male mice. We did not observe a difference of body weight loss in female mice. The body composition remained unchanged between TLR4IEC−/− and TLR4IEC+/+ mice in both sexes. In both sexes, ABA TLR4IEC+/+ mice exhibited an increase of food-anticipatory activity, as well as an increase of immobility time during the open field test. However, female TLR4IEC−/− mice showed a decrease of the time spent at the centre and an increase of the time spent at the periphery of the open field area, whereas we did not observe differences in the male mice. In conclusion, the invalidation of TLR4 in IEC modified the response to the ABA model in a sex-dependent manner. Further studies should decipher the underlying mechanisms.
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Affiliation(s)
- Pauline Tirelle
- Université de Rouen Normandie, INSERM UMR 1073 “Nutrition, Inflammation and Microbiota–Gut–Brain Axis”, 76183 Rouen, France
- Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie, 76183 Rouen, France
| | - Colin Salaün
- Université de Rouen Normandie, INSERM UMR 1073 “Nutrition, Inflammation and Microbiota–Gut–Brain Axis”, 76183 Rouen, France
- Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie, 76183 Rouen, France
| | - Alexandre Kauffmann
- Université de Rouen Normandie, INSERM UMR 1073 “Nutrition, Inflammation and Microbiota–Gut–Brain Axis”, 76183 Rouen, France
- Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie, 76183 Rouen, France
| | - Christine Bôle-Feysot
- Université de Rouen Normandie, INSERM UMR 1073 “Nutrition, Inflammation and Microbiota–Gut–Brain Axis”, 76183 Rouen, France
- Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie, 76183 Rouen, France
| | - Charlène Guérin
- Université de Rouen Normandie, INSERM UMR 1073 “Nutrition, Inflammation and Microbiota–Gut–Brain Axis”, 76183 Rouen, France
- Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie, 76183 Rouen, France
| | - Marion Huré
- Université de Rouen Normandie, INSERM UMR 1073 “Nutrition, Inflammation and Microbiota–Gut–Brain Axis”, 76183 Rouen, France
- Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie, 76183 Rouen, France
| | - Alexis Goichon
- Université de Rouen Normandie, INSERM UMR 1073 “Nutrition, Inflammation and Microbiota–Gut–Brain Axis”, 76183 Rouen, France
- Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie, 76183 Rouen, France
| | - Asma Amamou
- Université de Rouen Normandie, INSERM UMR 1073 “Nutrition, Inflammation and Microbiota–Gut–Brain Axis”, 76183 Rouen, France
- Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie, 76183 Rouen, France
| | - Jonathan Breton
- Université de Rouen Normandie, INSERM UMR 1073 “Nutrition, Inflammation and Microbiota–Gut–Brain Axis”, 76183 Rouen, France
- Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie, 76183 Rouen, France
- Department of Nutrition, Rouen University Hospital, CHU Rouen, 76031 Rouen, France
| | - Jean-Luc do Rego
- Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie, 76183 Rouen, France
- Université de Rouen Normandie, INSERM US51-CNRS UAR2026, Animal Behavioural Platform, SCAC-HeRacLeS “High-Tech Research Infrastructures for Life”, 76183 Rouen, France
| | - Pierre Déchelotte
- Université de Rouen Normandie, INSERM UMR 1073 “Nutrition, Inflammation and Microbiota–Gut–Brain Axis”, 76183 Rouen, France
- Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie, 76183 Rouen, France
- Department of Nutrition, Rouen University Hospital, CHU Rouen, 76031 Rouen, France
| | - Najate Achamrah
- Université de Rouen Normandie, INSERM UMR 1073 “Nutrition, Inflammation and Microbiota–Gut–Brain Axis”, 76183 Rouen, France
- Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie, 76183 Rouen, France
- Department of Nutrition, Rouen University Hospital, CHU Rouen, 76031 Rouen, France
| | - Moïse Coëffier
- Université de Rouen Normandie, INSERM UMR 1073 “Nutrition, Inflammation and Microbiota–Gut–Brain Axis”, 76183 Rouen, France
- Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie, 76183 Rouen, France
- Department of Nutrition, Rouen University Hospital, CHU Rouen, 76031 Rouen, France
- Correspondence: ; Tel.: +33-23-5148240
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Signaling pathways in obesity: mechanisms and therapeutic interventions. Signal Transduct Target Ther 2022; 7:298. [PMID: 36031641 PMCID: PMC9420733 DOI: 10.1038/s41392-022-01149-x] [Citation(s) in RCA: 172] [Impact Index Per Article: 57.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 07/26/2022] [Accepted: 08/08/2022] [Indexed: 12/19/2022] Open
Abstract
Obesity is a complex, chronic disease and global public health challenge. Characterized by excessive fat accumulation in the body, obesity sharply increases the risk of several diseases, such as type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease, and is linked to lower life expectancy. Although lifestyle intervention (diet and exercise) has remarkable effects on weight management, achieving long-term success at weight loss is extremely challenging, and the prevalence of obesity continues to rise worldwide. Over the past decades, the pathophysiology of obesity has been extensively investigated, and an increasing number of signal transduction pathways have been implicated in obesity, making it possible to fight obesity in a more effective and precise way. In this review, we summarize recent advances in the pathogenesis of obesity from both experimental and clinical studies, focusing on signaling pathways and their roles in the regulation of food intake, glucose homeostasis, adipogenesis, thermogenesis, and chronic inflammation. We also discuss the current anti-obesity drugs, as well as weight loss compounds in clinical trials, that target these signals. The evolving knowledge of signaling transduction may shed light on the future direction of obesity research, as we move into a new era of precision medicine.
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20
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Akkermansia muciniphila Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism. Cells 2022; 11:cells11172666. [PMID: 36078075 PMCID: PMC9454966 DOI: 10.3390/cells11172666] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 08/17/2022] [Accepted: 08/25/2022] [Indexed: 11/16/2022] Open
Abstract
Anastomotic leakage is a major complication following colorectal surgery leading to peritonitis, complications, and mortality. Akkermansia muciniphila has shown beneficial effects on the gut barrier function. Whether A. muciniphila reduces peritonitis and mortality during colonic leakage is unknown. Whether A. muciniphila can directly modulate the expression of genes in the colonic mucosa in humans has never been studied. We investigated the effects of a pretreatment (14 days) with live A. muciniphila prior to surgical colonic perforation on peritonitis, mortality, and wound healing. We used mice with an inducible intestinal-epithelial-cell-specific deletion of MyD88 (IEC-MyD88 KO) to investigate the role of the innate immune system in this context. In a proof-of-concept pilot study, healthy humans were exposed to A. muciniphila for 2 h and colonic biopsies taken before and after colonic instillation for transcriptomic analysis. Seven days after colonic perforation, A.-muciniphila-treated mice had significantly lower mortality and severity of peritonitis. This effect was associated with significant improvements of wound histological healing scores, higher production of IL22, but no changes in the mucus layer thickness or genes involved in cell renewal, proliferation, or differentiation. All these effects were abolished in IEC-MyD88 KO mice. Finally, human subjects exposed to A. muciniphila exhibited an increased level of the bacterium at the mucus level 2 h after instillation and significant changes in the expression of different genes involved in the regulation of cell cycling, gene transcription, immunity, and inflammation in their colonic mucosa. A. muciniphila improves wound healing during transmural colonic wall defect through mechanisms possibly involving IL22 signaling and requiring MyD88 in the intestinal cells. In healthy humans, colonic administration of A. muciniphila is well tolerated and changes the expression of genes involved in the immune pathways.
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21
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Ji S, You Y, Peng B, Zhong T, Kuang Y, Li S, Du L, Chen L, Sun X, Dai J, Huang S, Wu Y, Liu Y. Multi-omics analysis reveals the metabolic regulators of duodenal low-grade inflammation in a functional dyspepsia model. Front Immunol 2022; 13:944591. [PMID: 36091013 PMCID: PMC9453867 DOI: 10.3389/fimmu.2022.944591] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Accepted: 07/28/2022] [Indexed: 11/27/2022] Open
Abstract
Several gastrointestinal phenotypes and impairment of duodenal mucosal barrier have been reported in clinical studies in patients with functional dyspepsia (FD). Due to the preferential colonization of the mucosa, intestinal microbes and their metabolites are commonly involved in host metabolism and immune responses. However, there are no studies on the intertwined correlation among multi-level data. For more comprehensive illustrating, a multi-omics analysis focusing on the duodenum was performed in the FD rat model. We found that differential microbiomes in the duodenum were significantly correlated with the biosynthesis of lipopolysaccharide and peptidoglycan. The innate immune response-related genes, which were upregulated in the duodenum, were associated with the TLR2/TLR4-NFκB signaling pathway. More importantly, arachidonyl ethanolamide (anandamide, AEA) and endocannabinoid analogues showed linear relationships with the FD phenotypes. Taken together, multi-level data from microbiome, transcriptome and metabolome reveal that AEA may regulate duodenal low-grade inflammation in FD. These results suggest an important cue of gut microbiome–endocannabinoid system axis in the pathogenesis of FD.
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Affiliation(s)
- Shuai Ji
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Yanting You
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Baizhao Peng
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Tianyu Zhong
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Yuxiang Kuang
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Shasha Li
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Lijing Du
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
| | - Liqian Chen
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Xiaomin Sun
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Jiaojiao Dai
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Suiping Huang
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
- *Correspondence: Yanyan Liu, ; Yuyao Wu, ; Suiping Huang,
| | - Yuyao Wu
- Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
- *Correspondence: Yanyan Liu, ; Yuyao Wu, ; Suiping Huang,
| | - Yanyan Liu
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
- *Correspondence: Yanyan Liu, ; Yuyao Wu, ; Suiping Huang,
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22
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Ding L, Ren S, Song Y, Zang C, Liu Y, Guo H, Yang W, Guan H, Liu J. Modulation of gut microbiota and fecal metabolites by corn silk among high-fat diet-induced hypercholesterolemia mice. Front Nutr 2022; 9:935612. [PMID: 35978956 PMCID: PMC9376456 DOI: 10.3389/fnut.2022.935612] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 07/01/2022] [Indexed: 11/18/2022] Open
Abstract
Corn silk (CS) is known to reduce cholesterol levels, but its underlying mechanisms remain elusive concerning the gut microbiota and metabolites. The aim of our work was to explore how altered gut microbiota composition and metabolite profile are influenced by CS intervention in mice using integrated 16S ribosomal RNA (rRNA) sequencing and an untargeted metabolomics methodology. The C57BL/6J mice were fed a normal control diet, a high-fat diet (HFD), and HFD supplemented with the aqueous extract of CS (80 mg/mL) for 8 weeks. HFD-induced chronic inflammation damage is alleviated by CS extract intervention and also resulted in a reduction in body weight, daily energy intake as well as serum and hepatic total cholesterol (TC) levels. In addition, CS extract altered gut microbial composition and regulated specific genera viz. Allobaculum, Turicibacter, Romboutsia, Streptococcus, Sporobacter, Christensenella, ClostridiumXVIII, and Rikenella. Using Spearman’s correlation analysis, we determined that Turicibacter and Rikenella were negatively correlated with hypercholesterolemia-related parameters. Fecal metabolomics analysis revealed that CS extract influences multiple metabolic pathways like histidine metabolism-related metabolites (urocanic acid, methylimidazole acetaldehyde, and methiodimethylimidazoleacetic acid), sphingolipid metabolism-related metabolites (sphinganine, 3-dehydrosphinganine, sphingosine), and some bile acids biosynthesis-related metabolites including chenodeoxycholic acid (CDCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), and glycoursodeoxycholic acid (GUDCA). As a whole, the present study indicates that the modifications in the gut microbiota and subsequent host bile acid metabolism may be a potential mechanism for the antihypercholesterolemic effects of CS extract.
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Affiliation(s)
- Lin Ding
- Department of Scientific Research, Science and Technology Achievement Transformation Center, Qiqihar Medical University, Qiqihar, China
| | - Shan Ren
- College of Basic Medical, Qiqihar Medical University, Qiqihar, China
| | - Yaoxin Song
- Department of Scientific Research, Science and Technology Achievement Transformation Center, Qiqihar Medical University, Qiqihar, China
| | - Chuangang Zang
- Department of Scientific Research, Science and Technology Achievement Transformation Center, Qiqihar Medical University, Qiqihar, China
| | - Yuchao Liu
- Department of Scientific Research, Science and Technology Achievement Transformation Center, Qiqihar Medical University, Qiqihar, China
| | - Hao Guo
- Department of Scientific Research, Science and Technology Achievement Transformation Center, Qiqihar Medical University, Qiqihar, China
| | - Wenqing Yang
- Department of Scientific Research, Science and Technology Achievement Transformation Center, Qiqihar Medical University, Qiqihar, China
| | - Hong Guan
- Department of Scientific Research, Science and Technology Achievement Transformation Center, Qiqihar Medical University, Qiqihar, China
| | - Jicheng Liu
- Department of Scientific Research, Science and Technology Achievement Transformation Center, Qiqihar Medical University, Qiqihar, China.,Qiqihar Academy of Medical Sciences, Qiqihar, China
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23
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Wang A, Guan B, Shao C, Zhao L, Li Q, Hao H, Gao Z, Chen K, Hou Y, Xu H. Qing-Xin-Jie-Yu Granule alleviates atherosclerosis by reshaping gut microbiota and metabolic homeostasis of ApoE-/- mice. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 103:154220. [PMID: 35675748 DOI: 10.1016/j.phymed.2022.154220] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 05/18/2022] [Accepted: 05/27/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Atherosclerosis (AS) is a key pathological factor in cardiovascular disease (CVD) and is characterized by high mortality and morbidity worldwide. Metabolic disorders, including pathoglycemia and dyslipidemia that lead to chronic inflammation, represent the prominent pathological characteristics of atherosclerotic CVD, Qing-Xin-Jie-Yu Granule (QXJYG) is a Chinese traditional decoction that has been clinically proven to be effective for patients with CVD. However, the underlying mechanisms have not been completely elucidated. PURPOSE To investigate the protective effects of QXJYG against AS and its potential mechanisms. METHODS QXJYG was orally administered at doses of 1.664 and 4.992 g·kg-1·d-1 in a high-fat diet (HFD)-induced AS model using ApoE-/- mice. Histopathological and immunohistochemical analyses, ELISA, untargeted and targeted metabolomics analysis, 16S rRNA analysis, and RT-qPCR were performed to identify the therapeutic effects and mechanisms of QXJYG in treating HFD-induced AS. RESULTS QXJYG retarded HFD-induced weight gain and reduced the increased serum levels of total cholesterol, triglycerides, and low-density lipoprotein-cholesterol, whereas high-dose QXJYG increased the serum level of high-density lipoprotein-cholesterol in HFD-fed ApoE-/- mice. Meanwhile, QXJYG reduced the serum levels, as well as aortas mRNA levels of the inflammatory cytokines, IL-1β and IL-6, which indicates that QXJYG is effective against metaflammation. Mechanistically, QXJYG reshaped the gut microbiota and its associated bile acids (BAs) metabolomic phenotype, partly by increasing the levels of BA synthesis enzymes, hepatic CYP7A1, and CYP27A1, while decreasing ileal FGF15 and β-Klotho mRNA expression, favoring facilitated de novo BAs synthesis and thereby driving cholesterol catabolic excretion. CONCLUSION Our findings indicate that QXJYG is effective against HFD-triggered chronic inflammation, and contributes to the alleviation of AS development, and the antiatherogenic properties of QXJYG may be partly due to the remodeling of the gut microbiota and BA metabolism. Although the results are encouraging, further clinical studies of anti-AS herbal medicines are required to elucidate the full potential of the gut microbiota and BA metabolism.
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Affiliation(s)
- Anlu Wang
- China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing 100091, China; National Clinical Research Center for Chinese Medicine Cardiology, Beijing 100091, China
| | - Baoyi Guan
- China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing 100091, China; National Clinical Research Center for Chinese Medicine Cardiology, Beijing 100091, China
| | - Chang Shao
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
| | - Lin Zhao
- China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing 100091, China; National Clinical Research Center for Chinese Medicine Cardiology, Beijing 100091, China
| | - Qiuyi Li
- China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing 100091, China; National Clinical Research Center for Chinese Medicine Cardiology, Beijing 100091, China
| | - Haiping Hao
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
| | - Zhuye Gao
- China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing 100091, China; National Clinical Research Center for Chinese Medicine Cardiology, Beijing 100091, China
| | - Keji Chen
- China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing 100091, China; National Clinical Research Center for Chinese Medicine Cardiology, Beijing 100091, China
| | - Yuanlong Hou
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
| | - Hao Xu
- China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing 100091, China; National Clinical Research Center for Chinese Medicine Cardiology, Beijing 100091, China.
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24
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Wu Z, Xu C, Zheng T, Li Q, Yang S, Shao J, Guan W, Zhang S. A critical role of AMP-activated protein kinase in regulating intestinal nutrient absorption, barrier function, and intestinal diseases. J Cell Physiol 2022; 237:3705-3716. [PMID: 35892164 DOI: 10.1002/jcp.30841] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 07/12/2022] [Accepted: 07/15/2022] [Indexed: 02/06/2023]
Abstract
As one of the most important organs in animals, the intestine is responsible for nutrient absorption and acts as a barrier between the body and the environment. Intestinal physiology and function require the participation of energy. 5'-adenosine monophosphate-activated protein kinase (AMPK), a classical and highly expressed energy regulator in intestinal cells, regulates the process of nutrient absorption and barrier function and is also involved in the therapy of intestinal diseases. Studies have yielded findings that AMPK regulates the absorption of glucose, amino acids, and fatty acids in the intestine primarily by regulating transportation systems, as we detailed here. Moreover, AMPK is involved in the regulation of the intestinal mechanical barrier and immune barrier through manipulating the expression of tight junctions, antimicrobial peptides, and secretory immunoglobulins. In addition, AMPK also participates in the regulation of intestinal diseases, which indicates that AMPK is a promising therapeutic target for intestinal diseases and cancer. In this review, we summarized the current understanding regarding how AMPK regulates intestinal nutrient absorption, barrier function, and intestinal diseases.
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Affiliation(s)
- Zhihui Wu
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Chengfei Xu
- School of Clinical Medicine, Chengdu Medical College, Chengdu, China
| | - Tenghui Zheng
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Qihui Li
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Siwang Yang
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Jiayuan Shao
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Wutai Guan
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China.,College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China
| | - Shihai Zhang
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China.,College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China.,Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China
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25
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Li Y, Wei M, Yuan Q, Liu Y, Tian T, Hou L, Zhang J. MyD88 in hepatic stellate cells promotes the development of alcoholic fatty liver via the AKT pathway. J Mol Med (Berl) 2022; 100:1071-1085. [PMID: 35708745 DOI: 10.1007/s00109-022-02196-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 03/22/2022] [Accepted: 03/28/2022] [Indexed: 10/18/2022]
Abstract
Myeloid differentiation primary response gene 88 (MyD88), an adaptor protein in the Toll-like receptors (TLRs) signalling pathway, is expressed in various liver cells including hepatocytes, Kupffer cells and hepatic stellate cells (HSCs). And yet, the functional role of MyD88 in HSCs is poorly elucidated in alcoholic fatty liver (AFL). Here, to study the functional role of MyD88 in HSCs and the molecular mechanism related to the development of AFL, chronic-binge ethanol mouse models were established in mice with specific MyD88 knockout in quiescent (MyD88GFAP-KO) and activated HSCs (MyD88SMA-KO), respectively. Our results clearly showed an elevated expression of MyD88 in liver tissues of ethanol treated mouse model which harbours the wild type. Intriguingly, ethanol treatment profoundly inhibited inflammation in both MyD88GFAP-KO and MyD88SMA-KO mice, but the suppression of lipogenesis was only observed in MyD88GFAP-KO mice. Molecularly, our study indicated that MyD88 induced osteopontin (OPN) secretion in HSCs, which consequently resulted in activation of AKT signalling pathway and accumulation of fat in hepatocytes. Additionally, our data also suggested that OPN promoted inflammation by activating p-STAT1. Thus, targeting MyD88 may be a potentially represent a promising strategy for the prevention and treatment of AFL. KEY MESSAGES: The expression of MyD88 in HSCs was significantly increased in ethanol-induced liver tissues of wild-type mice. MyD88 deficiency in quiescent HSCs inhibited inflammation and lipogenesis under the ethanol feeding condition. MyD88 deficiency in activated HSCs only inhibited inflammation under the ethanol feeding condition. MyD88 promoted the OPN secretion of HSCs, which further activated the AKT signalling pathway of hepatocytes and upregulated lipogenic gene expression to promote fat accumulation. OPN also promotes inflammation by activating p-STAT1.
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Affiliation(s)
- Yukun Li
- The College of Life Science and Bioengineering, Beijing Jiaotong University, Beijing, People's Republic of China
| | - Miaomiao Wei
- The College of Life Science and Bioengineering, Beijing Jiaotong University, Beijing, People's Republic of China
| | - Qi Yuan
- The College of Life Science and Bioengineering, Beijing Jiaotong University, Beijing, People's Republic of China
| | - Yu Liu
- The College of Life Science and Bioengineering, Beijing Jiaotong University, Beijing, People's Republic of China
| | - Tian Tian
- The College of Life Science and Bioengineering, Beijing Jiaotong University, Beijing, People's Republic of China
| | - Lingling Hou
- The College of Life Science and Bioengineering, Beijing Jiaotong University, Beijing, People's Republic of China.
| | - Jinhua Zhang
- The College of Life Science and Bioengineering, Beijing Jiaotong University, Beijing, People's Republic of China.
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26
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Chen J, Liu Y, Luo H, Chen G, Zheng Z, Wang T, Hu X, Zhao Y, Tang J, Su C, Zha L. Inflammation Induced by Lipopolysaccharide and Palmitic Acid Increases Cholesterol Accumulation via Enhancing Myeloid Differentiation Factor 88 Expression in HepG2 Cells. Pharmaceuticals (Basel) 2022; 15:813. [PMID: 35890112 PMCID: PMC9322353 DOI: 10.3390/ph15070813] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 06/21/2022] [Accepted: 06/27/2022] [Indexed: 02/01/2023] Open
Abstract
Recently, multiple studies have shown that chronic inflammation disturbs cholesterol homeostasis and promotes its accumulation in the liver. The underlying molecular mechanism remains to be revealed. The relationship between the toll-like receptor 4 (TLR4) inflammatory signaling pathway and cholesterol accumulation was investigated in HepG2 cells treated with lipopolysaccharide (LPS) or palmitic acid (PA) for different lengths of time. In addition, the effects of pretreatment with 20μmol/L ST2825 (MyD88 inhibitor) were also studied in LPS- or PA-treated HepG2 cells and myeloid differentiation factor 88 (MyD88)-overexpressing HEK293T cells. The intracellular total and free cholesterol levels were measured using a commercial kit and filipin staining, respectively. The expression levels of sterol regulatory element-binding protein-2 (SREBP-2) and components in the TLR4 signaling pathway were determined using Western blotting. The treatments with LPS for 12 h and with PA for 24 h significantly increased the contents of intracellular total and free cholesterol, as well as the expression levels of SREBP-2 and components in the TLR4 signaling pathway. The inhibition of MyD88 by ST2825 significantly decreased the cholesterol content and the expression levels of SREBP-2 and components of the TLR4/MyD88/NF-κB pathway in HepG2 cells, as well as MyD88-overexpressing HEK293T cells. These results indicated that LPS and PA treatments increase SREBP-2-mediated cholesterol accumulation via the activation of the TLR4/MyD88/NF-κB signaling pathway in HepG2 cells.
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Affiliation(s)
- Junbin Chen
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China; (J.C.); (Y.L.); (H.L.); (Z.Z.); (Y.Z.); (J.T.); (C.S.)
| | - Yuguo Liu
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China; (J.C.); (Y.L.); (H.L.); (Z.Z.); (Y.Z.); (J.T.); (C.S.)
| | - Huiyu Luo
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China; (J.C.); (Y.L.); (H.L.); (Z.Z.); (Y.Z.); (J.T.); (C.S.)
| | - Guoxun Chen
- Department of Nutrition, University of Tennessee at Knoxville, Knoxville, TN 37996, USA; (G.C.); (T.W.); (X.H.)
| | - Zhongdaixi Zheng
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China; (J.C.); (Y.L.); (H.L.); (Z.Z.); (Y.Z.); (J.T.); (C.S.)
| | - Tiannan Wang
- Department of Nutrition, University of Tennessee at Knoxville, Knoxville, TN 37996, USA; (G.C.); (T.W.); (X.H.)
| | - Xinge Hu
- Department of Nutrition, University of Tennessee at Knoxville, Knoxville, TN 37996, USA; (G.C.); (T.W.); (X.H.)
| | - Yue Zhao
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China; (J.C.); (Y.L.); (H.L.); (Z.Z.); (Y.Z.); (J.T.); (C.S.)
| | - Jiaqi Tang
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China; (J.C.); (Y.L.); (H.L.); (Z.Z.); (Y.Z.); (J.T.); (C.S.)
| | - Chuhong Su
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China; (J.C.); (Y.L.); (H.L.); (Z.Z.); (Y.Z.); (J.T.); (C.S.)
| | - Longying Zha
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China; (J.C.); (Y.L.); (H.L.); (Z.Z.); (Y.Z.); (J.T.); (C.S.)
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27
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Srivastava RK, Lutz B, Ruiz de Azua I. The Microbiome and Gut Endocannabinoid System in the Regulation of Stress Responses and Metabolism. Front Cell Neurosci 2022; 16:867267. [PMID: 35634468 PMCID: PMC9130962 DOI: 10.3389/fncel.2022.867267] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 03/14/2022] [Indexed: 11/26/2022] Open
Abstract
The endocannabinoid system, with its receptors and ligands, is present in the gut epithelium and enteroendocrine cells, and is able to modulate brain functions, both indirectly through circulating gut-derived factors and directly through the vagus nerve, finally acting on the brain’s mechanisms regarding metabolism and behavior. The gut endocannabinoid system also regulates gut motility, permeability, and inflammatory responses. Furthermore, microbiota composition has been shown to influence the activity of the endocannabinoid system. This review examines the interaction between microbiota, intestinal endocannabinoid system, metabolism, and stress responses. We hypothesize that the crosstalk between microbiota and intestinal endocannabinoid system has a prominent role in stress-induced changes in the gut-brain axis affecting metabolic and mental health. Inter-individual differences are commonly observed in stress responses, but mechanisms underlying resilience and vulnerability to stress are far from understood. Both gut microbiota and the endocannabinoid system have been implicated in stress resilience. We also discuss interventions targeting the microbiota and the endocannabinoid system to mitigate metabolic and stress-related disorders.
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Affiliation(s)
- Raj Kamal Srivastava
- Department of Zoology, Indira Gandhi National Tribal University, Anuppur, India
- *Correspondence: Raj Kamal Srivastava,
| | - Beat Lutz
- Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- Leibniz Institute for Resilience Research (LIR), Mainz, Germany
| | - Inigo Ruiz de Azua
- Leibniz Institute for Resilience Research (LIR), Mainz, Germany
- Inigo Ruiz de Azua,
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28
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Abstract
The gut microbiota is now considered as one of the key elements contributing to the regulation of host health. Virtually all our body sites are colonised by microbes suggesting different types of crosstalk with our organs. Because of the development of molecular tools and techniques (ie, metagenomic, metabolomic, lipidomic, metatranscriptomic), the complex interactions occurring between the host and the different microorganisms are progressively being deciphered. Nowadays, gut microbiota deviations are linked with many diseases including obesity, type 2 diabetes, hepatic steatosis, intestinal bowel diseases (IBDs) and several types of cancer. Thus, suggesting that various pathways involved in immunity, energy, lipid and glucose metabolism are affected.In this review, specific attention is given to provide a critical evaluation of the current understanding in this field. Numerous molecular mechanisms explaining how gut bacteria might be causally linked with the protection or the onset of diseases are discussed. We examine well-established metabolites (ie, short-chain fatty acids, bile acids, trimethylamine N-oxide) and extend this to more recently identified molecular actors (ie, endocannabinoids, bioactive lipids, phenolic-derived compounds, advanced glycation end products and enterosynes) and their specific receptors such as peroxisome proliferator-activated receptor alpha (PPARα) and gamma (PPARγ), aryl hydrocarbon receptor (AhR), and G protein-coupled receptors (ie, GPR41, GPR43, GPR119, Takeda G protein-coupled receptor 5).Altogether, understanding the complexity and the molecular aspects linking gut microbes to health will help to set the basis for novel therapies that are already being developed.
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Affiliation(s)
- Willem M de Vos
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland,Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria
| | - Matthias Van Hul
- Louvain Drug Research Institute (LDRI), Metabolism and Nutrition research group (MNUT), UCLouvain, Université catholique de Louvain, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), Brussels, Belgium
| | - Patrice D Cani
- Louvain Drug Research Institute (LDRI), Metabolism and Nutrition research group (MNUT), UCLouvain, Université catholique de Louvain, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), Brussels, Belgium
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Qiu J, Ma Y, Qiu J. Regulation of intestinal immunity by dietary fatty acids. Mucosal Immunol 2022; 15:846-856. [PMID: 35821290 DOI: 10.1038/s41385-022-00547-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Revised: 06/28/2022] [Accepted: 06/28/2022] [Indexed: 02/04/2023]
Abstract
Dietary fatty acids are absorbed through the intestine and are fundamental for cellular energy provision and structural formation. Dietary fatty acids profoundly affect intestinal immunity and influence the development and progression of inflammatory bowel disease, intestinal infections and tumors. Although different types of fatty acids exert differential roles in intestinal immunity, a western diet, rich in saturated fatty acids with abundant carbohydrates and studied as high-fat diet (HFD) in animal experiments, disturbs intestinal homeostasis and plays a pathogenic role in intestinal inflammatory diseases. Here, we review recent findings on the regulation of intestinal immunity by dietary fatty acids, focusing on HFD. We summarize HFD-altered immune responses leading to susceptibility to intestinal pathology and dissect the mechanisms involving the impact of HFD on immune cells, intestinal epithelial cells and the microbiota. Understanding the perturbation of intestinal immunity by HFD will provide new strategies for prevention and treatment of intestinal inflammatory diseases.
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Affiliation(s)
- Jinxin Qiu
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
| | - Yanhui Ma
- Department of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
| | - Ju Qiu
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
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Abstract
The gut microbiota is now considered as one of the key elements contributing to the regulation of host health. Virtually all our body sites are colonised by microbes suggesting different types of crosstalk with our organs. Because of the development of molecular tools and techniques (ie, metagenomic, metabolomic, lipidomic, metatranscriptomic), the complex interactions occurring between the host and the different microorganisms are progressively being deciphered. Nowadays, gut microbiota deviations are linked with many diseases including obesity, type 2 diabetes, hepatic steatosis, intestinal bowel diseases (IBDs) and several types of cancer. Thus, suggesting that various pathways involved in immunity, energy, lipid and glucose metabolism are affected.In this review, specific attention is given to provide a critical evaluation of the current understanding in this field. Numerous molecular mechanisms explaining how gut bacteria might be causally linked with the protection or the onset of diseases are discussed. We examine well-established metabolites (ie, short-chain fatty acids, bile acids, trimethylamine N-oxide) and extend this to more recently identified molecular actors (ie, endocannabinoids, bioactive lipids, phenolic-derived compounds, advanced glycation end products and enterosynes) and their specific receptors such as peroxisome proliferator-activated receptor alpha (PPARα) and gamma (PPARγ), aryl hydrocarbon receptor (AhR), and G protein-coupled receptors (ie, GPR41, GPR43, GPR119, Takeda G protein-coupled receptor 5).Altogether, understanding the complexity and the molecular aspects linking gut microbes to health will help to set the basis for novel therapies that are already being developed.
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Affiliation(s)
- Willem M de Vos
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria
| | - Matthias Van Hul
- Louvain Drug Research Institute (LDRI), Metabolism and Nutrition research group (MNUT), UCLouvain, Université catholique de Louvain, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), Brussels, Belgium
| | - Patrice D Cani
- Louvain Drug Research Institute (LDRI), Metabolism and Nutrition research group (MNUT), UCLouvain, Université catholique de Louvain, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), Brussels, Belgium
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31
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Li W, Lai K, Chopra N, Zheng Z, Das A, Diwan AD. Gut-disc axis: A cause of intervertebral disc degeneration and low back pain? EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2022; 31:917-925. [PMID: 35286474 DOI: 10.1007/s00586-022-07152-8] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 01/29/2022] [Accepted: 02/10/2022] [Indexed: 02/07/2023]
Abstract
PURPOSE Low back pain (LBP), a widely prevalent and costly disease around the world, is mainly caused by intervertebral disc (IVD) degeneration (IDD). Although numerous factors may trigger this degenerative process, microbiome dysbiosis has recently been implicated as one of the likely causes. However, the exact relationship between the microbiome and IDD is not well understood. This review summarizes the potential mechanisms and discusses microbiome dysbiosis's possible influence on IDD and LBP. METHODS Prospective literature review. RESULTS Alterations in microbiome composition and host responses to the microbiota causing pathological bone development and involution, led to the concept of gut-bone marrow axis and gut-bone axis. Moreover, the concept of the gut-disc axis was also proposed to explain the microbiome's role in IDD and LBP. According to the existing evidence, the microbiome could be an important factor for inducing and aggravating IDD through changing or regulating the outside and inside microenvironment of the IVD. Three potential mechanisms by which the gut microbiota can induce IVD and cause LBP are: (1) translocation of the bacteria across the gut epithelial barrier and into the IVD, (2) regulation of the mucosal and systemic immune system, and (3) regulation of nutrient absorption and metabolites formation at the gut epithelium and its diffusion into the IVD. Furthermore, to investigate whether IVD is initiated by pathogenic bacteria and establish the correlation between the presence of certain microbial groups with the disease in question, microbiome diversity analysis based on16S rRNA data can be used to characterise stool/blood microbiota from IVD patients. CONCLUSION Future studies on microbiome, fungi and viruses in IDD is necessary to revolutionize our thinking about their possible role in the development of IVD diseases. Furthermore, we believe that inflammation inhibition and interruption of amplification of cascade reaction in IVD by targeting the gut and IVD microbiome is worthwhile for the treatment of IDD and LBP. LEVEL OF EVIDENCE I Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.
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Affiliation(s)
- Wentian Li
- Spine Labs, St. George & Sutherland Clinical School, University of New South Wales, Kogarah, NSW, 2217, Australia
| | - Kaitao Lai
- Charles Perkins Centre, School of Medical Sciences, The University of Sydney, Camperdown, NSW, 2006, Australia
| | - Neha Chopra
- Spine Service, St. George Private Hospital, Kogarah, NSW, 2217, Australia
| | - Zhaomin Zheng
- Spine Labs, St. George & Sutherland Clinical School, University of New South Wales, Kogarah, NSW, 2217, Australia
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Abhirup Das
- Spine Labs, St. George & Sutherland Clinical School, University of New South Wales, Kogarah, NSW, 2217, Australia.
- Spine Service, St. George Private Hospital, Kogarah, NSW, 2217, Australia.
| | - Ashish D Diwan
- Spine Labs, St. George & Sutherland Clinical School, University of New South Wales, Kogarah, NSW, 2217, Australia
- Spine Service, St. George Private Hospital, Kogarah, NSW, 2217, Australia
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Almeida PP, Valdetaro L, Thomasi BBDM, Stockler-Pinto MB, Tavares-Gomes AL. High-fat diets on the enteric nervous system: Possible interactions and mechanisms underlying dysmotility. Obes Rev 2022; 23:e13404. [PMID: 34873814 DOI: 10.1111/obr.13404] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/25/2021] [Accepted: 11/15/2021] [Indexed: 01/09/2023]
Abstract
Obesity is a chronic disease that affects various physiological systems. Among them, the gastrointestinal tract appears to be a main target of this disease. High-fat diet (HFD) animal models can help recapitulate the classic signs of obesity and present a series of gastrointestinal alterations, mainly dysmotility. Because intestinal motility is governed by the enteric nervous system (ENS), enteric neurons, and glial cells have been studied in HFD models. Given the importance of the ENS in general gut physiology, this review aims to discuss the relationship between HFD-induced neuroplasticity and gut dysmotility observed in experimental models. Furthermore, we highlight components of the gut environment that might influence enteric neuroplasticity, including gut microbiota, enteric glio-epithelial unit, serotonin release, immune cells, and disturbances such as inflammation and oxidative stress.
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Affiliation(s)
| | - Luisa Valdetaro
- Postgraduate Program in Neurosciences, Fluminense Federal University, Niterói, Brazil
| | | | - Milena Barcza Stockler-Pinto
- Postgraduate Program in Cardiovascular Sciences, Fluminense Federal University, Niterói, Brazil.,Postgraduate Program in Nutrition Sciences, Fluminense Federal University, Niterói, Brazil
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Abuqwider J, Altamimi M, Mauriello G. Limosilactobacillus reuteri in Health and Disease. Microorganisms 2022; 10:microorganisms10030522. [PMID: 35336098 PMCID: PMC8953724 DOI: 10.3390/microorganisms10030522] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/22/2022] [Accepted: 02/24/2022] [Indexed: 02/01/2023] Open
Abstract
Limosilactobacillus reuteri is a microorganism with valuable probiotic qualities that has been widely employed in humans to promote health. It is a well-studied probiotic bacterium that exerts beneficial health effects due to several metabolic mechanisms that enhance the production of anti-inflammatory cytochines and modulate the gut microbiota by the production of antimicrobial molecules, including reuterin. This review provides an overview of the data that support the role of probiotic properties, and the antimicrobial and immunomodulatory effects of some L. reuteri strains in relation to their metabolite production profile on the amelioration of many diseases and disorders. Although the results discussed in this paper are strain dependent, they show that L. reuteri, by different mechanisms and various metabolites, may control body weight and obesity, improve insulin sensitivity and glucose homeostasis, increase gut integrity and immunomodulation, and attenuate hepatic disorders. Gut microbiota modulation by ingesting probiotic L. reuteri strains could be a promising preventative and therapeutic approach against many diseases and disorders.
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Affiliation(s)
- Jumana Abuqwider
- Department of Agricultural Science, University of Naples Federico II, 80049 Naples, Italy;
| | - Mohammad Altamimi
- Department of Nutrition and Food Technology, Faculty of Agriculture and Veterinary Medicine, An-Najah National University, Nablus P.O. Box 7, Palestine;
| | - Gianluigi Mauriello
- Department of Agricultural Science, University of Naples Federico II, 80049 Naples, Italy;
- Correspondence: ; Tel.: +39-081-2539452
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Xiao Y, Li K, Bian J, Liu H, Zhai X, El‐Omar E, Han L, Gong L, Wang M. Urolithin A attenuates diabetes‐associated cognitive impairment by ameliorating intestinal barrier dysfunction via N‐glycan biosynthesis pathway. Mol Nutr Food Res 2022; 66:e2100863. [DOI: 10.1002/mnfr.202100863] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 01/24/2022] [Indexed: 11/05/2022]
Affiliation(s)
- Yao Xiao
- College of Food Science and Engineering Northwest A & F University Yangling Shaanxi 712100 China
| | - Kailin Li
- College of Food Science and Engineering Northwest A & F University Yangling Shaanxi 712100 China
| | - Ji Bian
- Kolling Institute Sydney Medical School Royal North Shore Hospital University of Sydney St. Leonards NSW 2065 Australia
| | - Hang Liu
- School of Life Sciences and Biotechnology Shanghai Jiao Tong University Shanghai Center for Systems Biomedicine Shanghai 200240 China
| | - Xiaotong Zhai
- College of Food Science and Engineering Northwest A & F University Yangling Shaanxi 712100 China
- Academy of National Food and Strategic Reserves Administration No.11 Baiwanzhuang Street Beijing 100037 China
| | - Emad El‐Omar
- Microbiome Research Centre St George and Sutherland Clinical School University of New South Wales Sydney Australia
| | - Lin Han
- College of Food Science and Engineering Northwest A & F University Yangling Shaanxi 712100 China
| | - Lan Gong
- Microbiome Research Centre St George and Sutherland Clinical School University of New South Wales Sydney Australia
| | - Min Wang
- College of Food Science and Engineering Northwest A & F University Yangling Shaanxi 712100 China
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35
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Mata-Martínez P, Bergón-Gutiérrez M, del Fresno C. Dectin-1 Signaling Update: New Perspectives for Trained Immunity. Front Immunol 2022; 13:812148. [PMID: 35237264 PMCID: PMC8882614 DOI: 10.3389/fimmu.2022.812148] [Citation(s) in RCA: 93] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 01/20/2022] [Indexed: 12/12/2022] Open
Abstract
The C-type lectin receptor Dectin-1 was originally described as the β-glucan receptor expressed in myeloid cells, with crucial functions in antifungal responses. However, over time, different ligands both of microbial-derived and endogenous origin have been shown to be recognized by Dectin-1. The outcomes of this recognition are diverse, including pro-inflammatory responses such as cytokine production, reactive oxygen species generation and phagocytosis. Nonetheless, tolerant responses have been also attributed to Dectin-1, depending on the specific ligand engaged. Dectin-1 recognition of their ligands triggers a plethora of downstream signaling pathways, with complex interrelationships. These signaling routes can be modulated by diverse factors such as phosphatases or tetraspanins, resulting either in pro-inflammatory or regulatory responses. Since its first depiction, Dectin-1 has recently gained a renewed attention due to its role in the induction of trained immunity. This process of long-term memory of innate immune cells can be triggered by β-glucans, and Dectin-1 is crucial for its initiation. The main signaling pathways involved in this process have been described, although the understanding of the above-mentioned complexity in the β-glucan-induced trained immunity is still scarce. In here, we have reviewed and updated all these factors related to the biology of Dectin-1, highlighting the gaps that deserve further research. We believe on the relevance to fully understand how this receptor works, and therefore, how we could harness it in different pathological conditions as diverse as fungal infections, autoimmunity, or cancer.
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Affiliation(s)
| | | | - Carlos del Fresno
- Immune response and Immunomodulation Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain
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36
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Antidiabetic Effects of Pediococcus acidilactici pA1c on HFD-Induced Mice. Nutrients 2022; 14:nu14030692. [PMID: 35277051 PMCID: PMC8839473 DOI: 10.3390/nu14030692] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/28/2022] [Accepted: 01/28/2022] [Indexed: 12/11/2022] Open
Abstract
Prediabetes (PreD), which is associated with impaired glucose tolerance and fasting blood glucose, is a potential risk factor for type 2 diabetes mellitus (T2D). Growing evidence suggests the role of the gastrointestinal microbiota in both PreD and T2D, which opens the possibility for a novel nutritional approach, based on probiotics, for improving glucose regulation and delaying disease progression of PreD to T2D. In this light, the present study aimed to assess the antidiabetic properties of Pediococcus acidilactici (pA1c) in a murine model of high-fat diet (HFD)-induced T2D. For that purpose, C57BL/6 mice were given HFD enriched with either probiotic (1 × 1010 CFU/day) or placebo for 12 weeks. We determined body weight, fasting blood glucose, glucose tolerance, HOMA-IR and HOMA-β index, C-peptide, GLP-1, leptin, and lipid profile. We also measured hepatic gene expression (G6P, PEPCK, GCK, IL-1β, and IL-6) and examined pancreatic and intestinal histology (% of GLP-1+ cells, % of goblet cells and villus length). We found that pA1c supplementation significantly attenuated body weight gain, mitigated glucose dysregulation by reducing fasting blood glucose levels, glucose tolerance test, leptin levels, and insulin resistance, increased C-peptide and GLP-1 levels, enhanced pancreatic function, and improved intestinal histology. These findings indicate that pA1c improved HFD-induced T2D derived insulin resistance and intestinal histology, as well as protected from body weight increase. Together, our study proposes that pA1c may be a promising new dietary management strategy to improve metabolic disorders in PreD and T2D.
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Song X, Wang L, Liu Y, Zhang X, Weng P, Liu L, Zhang R, Wu Z. The gut microbiota–brain axis: Role of the gut microbial metabolites of dietary food in obesity. Food Res Int 2022; 153:110971. [DOI: 10.1016/j.foodres.2022.110971] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 01/27/2022] [Accepted: 01/30/2022] [Indexed: 12/13/2022]
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Riedel S, Pheiffer C, Johnson R, Louw J, Muller CJF. Intestinal Barrier Function and Immune Homeostasis Are Missing Links in Obesity and Type 2 Diabetes Development. Front Endocrinol (Lausanne) 2022; 12:833544. [PMID: 35145486 PMCID: PMC8821109 DOI: 10.3389/fendo.2021.833544] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 12/27/2021] [Indexed: 12/19/2022] Open
Abstract
Noncommunicable diseases, such as type 2 diabetes (T2D), place a burden on healthcare systems worldwide. The rising prevalence of obesity, a major risk factor for T2D, is mainly attributed to the adoption of Westernized diets and lifestyle, which cause metabolic dysfunction and insulin resistance. Moreover, diet may also induce changes in the microbiota composition, thereby affecting intestinal immunity. The critical role of intestinal immunity and intestinal barrier function in the development of T2D is increasingly acknowledged, however, limited studies have investigated the link between intestinal function and metabolic disease. In this review, studies reporting specific roles of the intestinal immune system and intestinal epithelial cells (IECs) in metabolic disease are highlighted. Innate chemokine signaling, eosinophils, immunoglobulin A (IgA), T helper (Th) 17 cells and their cytokines were associated with obesity and/or dysregulated glucose homeostasis. Intestinal epithelial cells (IECs) emerged as critical modulators of obesity and glucose homeostasis through their effect on lipopolysaccharide (LPS) signaling and decontamination. Furthermore, IECs create a link between microbial metabolites and whole-body metabolic function. Future in depth studies of the intestinal immune system and IECs may provide new opportunities and targets to develop treatments and prevention strategies for obesity and T2D.
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Affiliation(s)
- Sylvia Riedel
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, South Africa
- Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, Tygerberg, South Africa
| | - Carmen Pheiffer
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, South Africa
- Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, Tygerberg, South Africa
- Department of Obstetrics and Gynaecology, University of Pretoria, Pretoria, South Africa
| | - Rabia Johnson
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, South Africa
- Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, Tygerberg, South Africa
| | - Johan Louw
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, South Africa
- Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, South Africa
| | - Christo J. F. Muller
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, South Africa
- Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, Tygerberg, South Africa
- Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, South Africa
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de Wouters d’Oplinter A, Rastelli M, Van Hul M, Delzenne NM, Cani PD, Everard A. Gut microbes participate in food preference alterations during obesity. Gut Microbes 2022; 13:1959242. [PMID: 34424831 PMCID: PMC8386729 DOI: 10.1080/19490976.2021.1959242] [Citation(s) in RCA: 61] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Hypothalamic regulations of food intake are altered during obesity. The dopaminergic mesocorticolimbic system, responsible for the hedonic response to food intake, is also affected. Gut microbes are other key players involved in obesity. Therefore, we investigated whether the gut microbiota plays a causal role in hedonic food intake alterations contributing to obesity. We transferred fecal material from lean or diet-induced obese mice into recipient mice and evaluated the hedonic food intake using a food preference test comparing the intake of control and palatable diets (HFHS, High-Fat High-Sucrose) in donor and recipient mice. Obese mice ate 58% less HFHS during the food preference test (p < 0.0001) than the lean donors, suggesting a dysregulation of the hedonic food intake during obesity. Strikingly, the reduction of the pleasure induced by eating during obesity was transferable through gut microbiota transplantation since obese gut microbiota recipient mice exhibited similar reduction in HFHS intake during the food preference test (40% reduction as compared to lean gut microbiota recipient mice, p < 0.01). This effect was associated with a consistent trend in modifications of dopaminergic markers expression in the striatum. We also pinpointed a highly positive correlation between HFHS intake and Parabacteroides (p < 0.0001), which could represent a potential actor involved in hedonic feeding probably through the gut-to-brain axis. We further demonstrated the key roles played by gut microbes in this paradigm since depletion of gut microbiota using broad-spectrum antibiotics also altered HFHS intake during food preference test in lean mice. In conclusion, we discovered that gut microbes regulate hedonic aspects of food intake. Our data demonstrate that gut microbiota modifications associated with obesity participate in dysregulations of the reward and hedonic components of the food intake. These data provide evidence that gut microbes could be an interesting therapeutic target to tackle hedonic disorders related to obesity.
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Affiliation(s)
- Alice de Wouters d’Oplinter
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), UCLouvain, Université Catholique De Louvain, Brussels, Belgium
| | - Marialetizia Rastelli
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), UCLouvain, Université Catholique De Louvain, Brussels, Belgium
| | - Matthias Van Hul
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), UCLouvain, Université Catholique De Louvain, Brussels, Belgium
| | - Nathalie M. Delzenne
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université Catholique De Louvain, Brussels, Belgium
| | - Patrice D. Cani
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), UCLouvain, Université Catholique De Louvain, Brussels, Belgium
| | - Amandine Everard
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), UCLouvain, Université Catholique De Louvain, Brussels, Belgium,CONTACT Amandine Everard UCLouvain, Université Catholique De Louvain, LDRI, Metabolism and Nutrition Research Group, Av. E. Mounier, 73 Box B1.73.11, B-1200Brussels, Belgium
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40
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Khan RN, Maner-Smith K, A. Owens J, Barbian ME, Jones RM, R. Naudin C. At the heart of microbial conversations: endocannabinoids and the microbiome in cardiometabolic risk. Gut Microbes 2022; 13:1-21. [PMID: 33896380 PMCID: PMC8078674 DOI: 10.1080/19490976.2021.1911572] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Cardiometabolic syndrome encompasses intertwined risk factors such as hypertension, dyslipidemia, elevated triglycerides, abdominal obesity, and other maladaptive metabolic and inflammatory aberrations. As the molecular mechanisms linking cardiovascular disease and metabolic disorders are investigated, endocannabinoids have emerged as molecules of interest. The endocannabinoid system (ECS) of biologically active lipids has been implicated in several conditions, including chronic liver disease, osteoporosis, and more recently in cardiovascular diseases. The gut microbiome is a major regulator of inflammatory and metabolic signaling in the host, and if disrupted, has the potential to drive metabolic and cardiovascular diseases. Extensive studies have unraveled the impact of the gut microbiome on host physiology, with recent reports showing that gut microbes exquisitely control the ECS, with significant influences on host metabolic and cardiac health. In this review, we outline how modulation of the gut microbiome affects host metabolism and cardiovascular health via the ECS, and how these findings could be exploited as novel therapeutic targets for various metabolic and cardiac diseases.
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Affiliation(s)
- Ramsha Nabihah Khan
- Division of Gastroenterology and Hepatology, Department of Pediatrics, Children’s Healthcare of Atlanta and Emory University, Atlanta, Georgia, USA
| | - Kristal Maner-Smith
- Emory Integrated Metabolomics and Lipidomics Core, Emory University, Atlanta, Georgia, USA
| | - Joshua A. Owens
- Division of Gastroenterology and Hepatology, Department of Pediatrics, Children’s Healthcare of Atlanta and Emory University, Atlanta, Georgia, USA
| | - Maria Estefania Barbian
- Division of Neonatology, Department of Pediatrics, Children’s Healthcare of Atlanta and Emory University, Atlanta, Georgia, USA
| | - Rheinallt M. Jones
- Division of Gastroenterology and Hepatology, Department of Pediatrics, Children’s Healthcare of Atlanta and Emory University, Atlanta, Georgia, USA
| | - Crystal R. Naudin
- Division of Gastroenterology and Hepatology, Department of Pediatrics, Children’s Healthcare of Atlanta and Emory University, Atlanta, Georgia, USA,CONTACT Crystal R. Naudin Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University School of Medicine, 615 Michael Street, Atlanta, GA30322, United States of America
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Rath E, Haller D. Intestinal epithelial cell metabolism at the interface of microbial dysbiosis and tissue injury. Mucosal Immunol 2022; 15:595-604. [PMID: 35534699 PMCID: PMC9259489 DOI: 10.1038/s41385-022-00514-x] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 03/16/2022] [Accepted: 04/05/2022] [Indexed: 02/07/2023]
Abstract
The intestinal epithelium represents the most regenerative tissue in the human body, located in proximity to the dense and functionally diverse microbial milieu of the microbiome. Episodes of tissue injury and incomplete healing of the intestinal epithelium are a prerequisite for immune reactivation and account for recurrent, chronically progressing phenotypes of inflammatory bowel diseases (IBD). Mitochondrial dysfunction and associated changes in intestinal epithelial functions are emerging concepts in the pathogenesis of IBD, suggesting impaired metabolic flexibility of epithelial cells affects the regenerative capacity of the intestinal tissue. Next to rendering the intestinal mucosa susceptible to inflammatory triggers, metabolic reprogramming of the epithelium is implicated in shaping adverse microbial environments. In this review, we introduce the concept of "metabolic injury" as a cell autonomous mechanism of tissue wounding in response to mitochondrial perturbation. Furthermore, we highlight epithelial metabolism as intersection of microbiome, immune cells and epithelial regeneration.
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Affiliation(s)
- Eva Rath
- grid.6936.a0000000123222966Technical University of Munich, Chair of Nutrition and Immunology, Freising-Weihenstephan, Germany
| | - Dirk Haller
- grid.6936.a0000000123222966Technical University of Munich, Chair of Nutrition and Immunology, Freising-Weihenstephan, Germany ,grid.6936.a0000000123222966Technical University of Munich, ZIEL Institute for Food & Health, Freising-Weihenstephan, Germany
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Osborn LJ, Orabi D, Goudzari M, Sangwan N, Banerjee R, Brown AL, Kadam A, Gromovsky AD, Linga P, Cresci GAM, Mak TD, Willard BB, Claesen J, Brown JM. A Single Human-Relevant Fast Food Meal Rapidly Reorganizes Metabolomic and Transcriptomic Signatures in a Gut Microbiota-Dependent Manner. IMMUNOMETABOLISM 2021; 3:e210029. [PMID: 34804604 PMCID: PMC8601658 DOI: 10.20900/immunometab20210029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND A major contributor to cardiometabolic disease is caloric excess, often a result of consuming low cost, high calorie fast food. Studies have demonstrated the pivotal role of gut microbes contributing to cardiovascular disease in a diet-dependent manner. Given the central contributions of diet and gut microbiota to cardiometabolic disease, we hypothesized that microbial metabolites originating after fast food consumption can elicit acute metabolic responses in the liver. METHODS We gave conventionally raised mice or mice that had their microbiomes depleted with antibiotics a single oral gavage of a liquified fast food meal or liquified control rodent chow meal. After four hours, mice were sacrificed and we used untargeted metabolomics of portal and peripheral blood, 16S rRNA gene sequencing, targeted liver metabolomics, and host liver RNA sequencing to identify novel fast food-derived microbial metabolites and their acute effects on liver function. RESULTS Several candidate microbial metabolites were enriched in portal blood upon fast food feeding, and were essentially absent in antibiotic-treated mice. Strikingly, at four hours post-gavage, fast food consumption resulted in rapid reorganization of the gut microbial community and drastically altered hepatic gene expression. Importantly, diet-driven reshaping of the microbiome and liver transcriptome was dependent on an intact microbial community and not observed in antibiotic ablated animals. CONCLUSIONS Collectively, these data suggest a single fast food meal is sufficient to reshape the gut microbial community in mice, yielding a unique signature of food-derived microbial metabolites. Future studies are in progress to determine the contribution of select metabolites to cardiometabolic disease progression and the translational relevance of these animal studies.
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Affiliation(s)
- Lucas J. Osborn
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA
| | - Danny Orabi
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA
- Department of General Surgery, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Maryam Goudzari
- Mass Spectrometry Core, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
| | - Naseer Sangwan
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
| | - Rakhee Banerjee
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
| | - Amanda L. Brown
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA
| | - Anagha Kadam
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
| | - Anthony D. Gromovsky
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA
| | - Pranavi Linga
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
| | - Gail A. M. Cresci
- Department of Inflammation and Immunity, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
| | - Tytus D. Mak
- Mass Spectrometry Data Center, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA
| | - Belinda B. Willard
- Mass Spectrometry Core, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
| | - Jan Claesen
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA
| | - J. Mark Brown
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA
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Cherkasova V, Kovalchuk O, Kovalchuk I. Cannabinoids and Endocannabinoid System Changes in Intestinal Inflammation and Colorectal Cancer. Cancers (Basel) 2021; 13:4353. [PMID: 34503163 PMCID: PMC8430689 DOI: 10.3390/cancers13174353] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 08/25/2021] [Indexed: 01/02/2023] Open
Abstract
Despite the multiple preventive measures and treatment options, colorectal cancer holds a significant place in the world's disease and mortality rates. The development of novel therapy is in critical need, and based on recent experimental data, cannabinoids could become excellent candidates. This review covered known experimental studies regarding the effects of cannabinoids on intestinal inflammation and colorectal cancer. In our opinion, because colorectal cancer is a heterogeneous disease with different genomic landscapes, the choice of cannabinoids for tumor prevention and treatment depends on the type of the disease, its etiology, driver mutations, and the expression levels of cannabinoid receptors. In this review, we describe the molecular changes of the endocannabinoid system in the pathologies of the large intestine, focusing on inflammation and cancer.
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Affiliation(s)
| | - Olga Kovalchuk
- Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 7X8, Canada;
| | - Igor Kovalchuk
- Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 7X8, Canada;
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Zhang Y, Li JX, Zhang Y, Wang YL. Intestinal microbiota participates in nonalcoholic fatty liver disease progression by affecting intestinal homeostasis. World J Clin Cases 2021; 9:6654-6662. [PMID: 34447812 PMCID: PMC8362529 DOI: 10.12998/wjcc.v9.i23.6654] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/25/2021] [Accepted: 06/22/2021] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a pathogenesis that has not been fully elucidated. With the development of the theory of the gut-liver axis and the deepening of related research, the role of the intestinal tract in the pathogenesis of NAFLD has been investigated more. Intestinal microbiota, intestinal metabolites, and intestinal epithelial and immune-based barriers constitute the intestinal environment, which uses crosstalk to maintain the homeostasis of the intestinal environment. This paper reviews the progress in the study of intestinal microbiota, intestinal environment, and NAFLD and suggests that repair of intestinal functional balance may be a new idea for early prevention and intervention of NAFLD.
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Affiliation(s)
- Yang Zhang
- Department of Gastroenterology, Dong Fang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China
| | - Jun-Xiang Li
- Department of Gastroenterology, Dong Fang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China
| | - Yan Zhang
- Department of Gastroenterology, Dong Fang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China
| | - Yun-Liang Wang
- Department of Gastroenterology, Dong Fang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China
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Abstract
Summary
The human microbiota has a tremendous effect on our health. In the last decades, our knowledge about interactions between bacteria and humans have grown greatly. Not only is it necessary for humans to synthesize vitamins, to have tight intestinal barriers or protect from pathogens, it also has an impact on our immune system and thus plays an important role in autoimmune diseases and prevention of excessive inflammatory response. The idea of probiotics is to restore the balance in humans digestive microbiota. There is a growing number of scientific papers that proves a positive impact of using probiotics in various diseases. However, there are still questions that need to be answered before probiotics play a bigger role in the treatment. This paper presents the information about the use of probiotics in most common diseases of gastrointestinal tract.
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46
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Liu F, Hou P, Zhang H, Tang Q, Xue C, Li RW. Food-grade carrageenans and their implications in health and disease. Compr Rev Food Sci Food Saf 2021; 20:3918-3936. [PMID: 34146449 DOI: 10.1111/1541-4337.12790] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 04/22/2021] [Accepted: 05/13/2021] [Indexed: 12/19/2022]
Abstract
Food additives, often used to guarantee the texture, shelf-life, taste, and appearance of processed foods, have gained widespread attention due to their increased link to the growing incidence of chronic diseases. As one of the most common additives, carrageenans have been used in human diets for hundreds of years. While classified as generally recognized as safe (GRAS) for human consumption, numerous studies since the 1980s have suggested that carrageenans, particularly those with random coil conformations, may have adverse effects on gastrointestinal health, including aggravating intestinal inflammation. While these studies have provided some evidence of adverse effects, the topic is still controversial. Some have suggested that the negative consequence of the consumption of carrageenans may be structure dependent. Furthermore, pre-existing conditions may predispose individuals to varied outcomes of carrageenan intake. In this review, structure-function relationships of various carrageenans in the context of food safety are discussed. We reviewed the molecular mechanisms by which carrageenans exert their biological effects. We summarized the findings associated with carrageenan intake in animal models and clinical trials. Moreover, we examined the interactions between carrageenans and the gut microbiome in the pathogenesis of gastrointestinal disorders. This review argues for personalized guidance on carrageenan intake based on individuals' health status. Future research efforts that aim to close the knowledge gap on the effect of low-dose and chronic carrageenan intake as well as interactions among food additives should be conducive to the improved safety profile of carrageenans in processed food products.
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Affiliation(s)
- Fang Liu
- College of Food Science and Engineering, Ocean University of China, Qingdao, China
| | - Pengfen Hou
- Affiliated Hospital of Qingdao Binhai University, Qingdao, China
| | - Hui Zhang
- College of Food Science and Engineering, Ocean University of China, Qingdao, China
| | - Qingjuan Tang
- College of Food Science and Engineering, Ocean University of China, Qingdao, China
| | - Changhu Xue
- College of Food Science and Engineering, Ocean University of China, Qingdao, China.,Laboratory of Marine Drugs and Biological Products, Pilot National Laboratory for Marine Science and Technology, Qingdao, China
| | - Robert W Li
- USDA-ARS Animal Genomics and Improvement Laboratory, Beltsville, Maryland, USA
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Cifarelli V, Appak-Baskoy S, Peche VS, Kluzak A, Shew T, Narendran R, Pietka KM, Cella M, Walls CW, Czepielewski R, Ivanov S, Randolph GJ, Augustin HG, Abumrad NA. Visceral obesity and insulin resistance associate with CD36 deletion in lymphatic endothelial cells. Nat Commun 2021; 12:3350. [PMID: 34099721 PMCID: PMC8184948 DOI: 10.1038/s41467-021-23808-3] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 05/13/2021] [Indexed: 12/18/2022] Open
Abstract
Disruption of lymphatic lipid transport is linked to obesity and type 2 diabetes (T2D), but regulation of lymphatic vessel function and its link to disease remain unclear. Here we show that intestinal lymphatic endothelial cells (LECs) have an increasing CD36 expression from lymphatic capillaries (lacteals) to collecting vessels, and that LEC CD36 regulates lymphatic integrity and optimizes lipid transport. Inducible deletion of CD36 in LECs in adult mice (Cd36ΔLEC) increases discontinuity of LEC VE-cadherin junctions in lacteals and collecting vessels. Cd36ΔLEC mice display slower transport of absorbed lipid, more permeable mesenteric lymphatics, accumulation of inflamed visceral fat and impaired glucose disposal. CD36 silencing in cultured LECs suppresses cell respiration, reduces VEGF-C-mediated VEGFR2/AKT phosphorylation and destabilizes VE-cadherin junctions. Thus, LEC CD36 optimizes lymphatic junctions and integrity of lymphatic lipid transport, and its loss in mice causes lymph leakage, visceral adiposity and glucose intolerance, phenotypes that increase risk of T2D. Genetic variants in CD36 have been associated with metabolic syndrome. Here, the authors found that lymphatic vessel integrity and lipid transport are influenced by CD36 expression, and lymphatic endothelial cell CD36 deficiency causes visceral obesity and insulin resistance, which are risk factors for metabolic syndrome and diabetes.
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Affiliation(s)
- Vincenza Cifarelli
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, USA.
| | - Sila Appak-Baskoy
- European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.,Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ-ZMBH Alliance), Heidelberg, Germany
| | - Vivek S Peche
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, USA
| | - Andrew Kluzak
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, USA
| | - Trevor Shew
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, USA
| | - Ramkumar Narendran
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, USA
| | - Kathryn M Pietka
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, USA
| | - Marina Cella
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, USA
| | - Curtis W Walls
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, USA
| | - Rafael Czepielewski
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, USA
| | - Stoyan Ivanov
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, USA
| | - Gwendalyn J Randolph
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, USA
| | - Hellmut G Augustin
- European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.,Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ-ZMBH Alliance), Heidelberg, Germany
| | - Nada A Abumrad
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, USA. .,Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, USA.
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Khan S, Luck H, Winer S, Winer DA. Emerging concepts in intestinal immune control of obesity-related metabolic disease. Nat Commun 2021; 12:2598. [PMID: 33972511 PMCID: PMC8110751 DOI: 10.1038/s41467-021-22727-7] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 03/22/2021] [Indexed: 12/19/2022] Open
Abstract
The intestinal immune system is an important modulator of glucose homeostasis and obesity-associated insulin resistance. Dietary factors, the intestinal microbiota and their metabolites shape intestinal immunity during obesity. The intestinal immune system in turn affects processes such as intestinal permeability, immune cell trafficking, and intestinal hormone availability, impacting systemic insulin resistance. Understanding these pathways might identify mechanisms underlying treatments for insulin resistance, such as metformin and bariatric surgery, or aid in developing new therapies and vaccination approaches. Here, we highlight evolving concepts centered on intestinal immunity, diet, and the microbiota to provide a working model of obesity-related metabolic disease.
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Affiliation(s)
- Saad Khan
- Department of Immunology, University of Toronto, Toronto, ON, Canada
- Division of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Hospital Research Institute (TGHRI), University Health Network, Toronto, ON, Canada
| | - Helen Luck
- Division of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Hospital Research Institute (TGHRI), University Health Network, Toronto, ON, Canada
| | - Shawn Winer
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
- Department of Laboratory Medicine, St. Michael's Hospital, Toronto, ON, Canada
| | - Daniel A Winer
- Department of Immunology, University of Toronto, Toronto, ON, Canada.
- Division of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Hospital Research Institute (TGHRI), University Health Network, Toronto, ON, Canada.
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
- Department of Pathology, University Health Network, Toronto, ON, Canada.
- Buck Institute for Research on Aging, Novato, CA, USA.
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Fan S, Raychaudhuri S, Page R, Shahinozzaman M, Obanda DN. Metagenomic insights into the effects of Urtica dioica vegetable on the gut microbiota of C57BL/6J obese mice, particularly the composition of Clostridia. J Nutr Biochem 2021; 91:108594. [PMID: 33545322 DOI: 10.1016/j.jnutbio.2021.108594] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 11/30/2020] [Accepted: 01/06/2021] [Indexed: 12/30/2022]
Abstract
Urtica dioica (UT) vegetable attenuates diet induced weight gain and insulin resistance. We hypothesized that UT imparts metabolic health by impacting the gut microbiota composition. We examined effects of UT on the cecal bacterial taxonomic signature of C57BL/6J mice fed isocaloric diets: a low-fat diet (LFD) with 10% fat, a high fat diet (HFD) with 45% fat or the HFD supplemented with 9% UT (HFUT). Among Firmicutes, the HFD had no significant impact on Clostridia, but increased Bacilli particularly genus Lactococcus and Lactobacillus. HFUT lowered Lactococcus but not Lactobacillus to levels of the LFD (P<.01; n=9). Further examination of Clostridia showed that HFUT increased genus Clostridium by over 2-fold particularly the species C. vincentii and C. disporicum and increased genus Turicibacter by three-fold (P<.05; n=9). Abundance of Clostridium and Turicibacter negatively correlated with body weight (P<.05; R2=0.42) and HOMA-IR (P<.05; R2=0.45). Turicibacter and Clostridium have been shown to be more abundant in lean phenotypes compared to obese. Clostridium impacts host phenotype by inducing intestinal T cell responses. The HFUT diet had no effect on members of Actinobacteria. Among Bacteroidetes, HFUT mainly increased proliferation of Bacteroides thetaiotaomicron (P<.05; n=9) with no significant impact on other groups. Functional analysis showed that HFUT enhanced bacterial beta-alanine and D-arginine metabolism both of which are associated with a lean phenotype and enhanced insulin sensitivity. We conclude that increasing the proliferation of Clostridium and Turicibacter and altering amino acid metabolism may be contributing mechanism(s) by which Urtica dioica impacts metabolic health.
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Affiliation(s)
- Si Fan
- University of Maryland, Department of Nutrition and Food Sciences, College Park, MD, USA
| | - Samnhita Raychaudhuri
- University of Maryland, Department of Nutrition and Food Sciences, College Park, MD, USA
| | - Ryan Page
- Louisiana State University, Department of Animal Sciences, Baton Rouge, LA, USA
| | - Md Shahinozzaman
- University of Maryland, Department of Nutrition and Food Sciences, College Park, MD, USA
| | - Diana N Obanda
- University of Maryland, Department of Nutrition and Food Sciences, College Park, MD, USA.
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50
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Sang T, Guo C, Guo D, Wu J, Wang Y, Wang Y, Chen J, Chen C, Wu K, Na K, Li K, Fang L, Guo C, Wang X. Suppression of obesity and inflammation by polysaccharide from sporoderm-broken spore of Ganoderma lucidum via gut microbiota regulation. Carbohydr Polym 2021; 256:117594. [DOI: 10.1016/j.carbpol.2020.117594] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 12/27/2020] [Accepted: 12/28/2020] [Indexed: 02/07/2023]
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