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Rondanelli M, Borromeo S, Cavioni A, Gasparri C, Gattone I, Genovese E, Lazzarotti A, Minonne L, Moroni A, Patelli Z, Razza C, Sivieri C, Valentini EM, Barrile GC. Therapeutic Strategies to Modulate Gut Microbial Health: Approaches for Chronic Metabolic Disorder Management. Metabolites 2025; 15:127. [PMID: 39997751 PMCID: PMC11857149 DOI: 10.3390/metabo15020127] [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: 12/02/2024] [Revised: 01/17/2025] [Accepted: 01/28/2025] [Indexed: 02/26/2025] Open
Abstract
Numerous recent studies have suggested that the composition of the intestinal microbiota can trigger metabolic disorders, such as diabetes, prediabetes, obesity, metabolic syndrome, sarcopenia, dyslipidemia, hyperhomocysteinemia, and non-alcoholic fatty liver disease. Since then, considerable effort has been made to understand the link between the composition of intestinal microbiota and metabolic disorders, as well as the role of probiotics in the modulation of the intestinal microbiota. The aim of this review was to summarize the reviews and individual articles on the state of the art regarding ideal therapy with probiotics and prebiotics in order to obtain the reversion of dysbiosis (alteration in microbiota) to eubiosis during metabolic diseases, such as diabetes, prediabetes, obesity, hyperhomocysteinemia, dyslipidemia, sarcopenia, and non-alcoholic fatty liver diseases. This review includes 245 eligible studies. In conclusion, a condition of dysbiosis, or in general, alteration of the intestinal microbiota, could be implicated in the development of metabolic disorders through different mechanisms, mainly linked to the release of pro-inflammatory factors. Several studies have already demonstrated the potential of using probiotics and prebiotics in the treatment of this condition, detecting significant improvements in the specific symptoms of metabolic diseases. These findings reinforce the hypothesis that a condition of dysbiosis can lead to a generalized inflammatory picture with negative consequences on different organs and systems. Moreover, this review confirms that the beneficial effects of probiotics on metabolic diseases are promising, but more research is needed to determine the optimal probiotic strains, doses, and administration forms for specific metabolic conditions.
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Affiliation(s)
- Mariangela Rondanelli
- Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy;
| | - Sara Borromeo
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Alessandro Cavioni
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Clara Gasparri
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Ilaria Gattone
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Elisa Genovese
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Alessandro Lazzarotti
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Leonardo Minonne
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Alessia Moroni
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Zaira Patelli
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Claudia Razza
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Claudia Sivieri
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Eugenio Marzio Valentini
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Gaetan Claude Barrile
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
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Gu X, Yuan L, Gan L, Zhang Z, Zhou S, Fu Z, Liu Y, Xin Z, Cheng S, Zhou X, Yan H, Wang Q. Understanding the Role of Exercise and Probiotic Interventions on Non-Alcoholic Fatty Liver Disease Alleviation in Zebrafish: Dialogue Between the Gut and Liver. Int J Mol Sci 2025; 26:1360. [PMID: 39941128 PMCID: PMC11818905 DOI: 10.3390/ijms26031360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 02/01/2025] [Accepted: 02/04/2025] [Indexed: 02/16/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), the most prevalent chronic liver illness, is characterized by hepatic steatosis. Exercise and probiotics can regulate the gut microbiota to treat NAFLD; however, their combined effects and the mechanisms of gut-liver communication remain unclear. Inconsistent results on probiotic efficacy further warrant investigation. In this study, zebrafish fed a high-fat diet (HFD) for six weeks were subjected to swimming exercise (HFDE), probiotic intervention (HFDP), or a combination of both (HFDEP) for 10 weeks to explore their effects on NAFLD and the corresponding mechanism. The results showed that NAFLD alleviation followed the order HFDEP > HFDE > HFDP. HFDEP and HFDE treatments effectively reduced Body Mass Index (BMI), relative liver weight, liver vacuolation density, lipid droplets in liver sections, triglyceride, free fatty acid, glucose, and pyruvic acid. In contrast, a single probiotic treatment had limited impact, suggesting a complementary role in NAFLD treatment. Glucose and fatty acid metabolism were central to the "gut-liver" axis. The reduced conversion of glucose to pyruvic acid, decreased fatty acid synthesis and esterification, and accelerated fatty acid transformation to CO2 contributed to NAFLD improvement under HFDE and HFDEP treatments. This study provides promising theoretical groundwork for potential prevention and treatment strategies for NAFLD.
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Affiliation(s)
- Xueyan Gu
- Physical Education College, Jiangxi Normal University, Nanchang 330022, China; (X.G.); (L.Y.); (S.Z.); (Z.F.); (S.C.); (X.Z.); (H.Y.)
| | - Liyan Yuan
- Physical Education College, Jiangxi Normal University, Nanchang 330022, China; (X.G.); (L.Y.); (S.Z.); (Z.F.); (S.C.); (X.Z.); (H.Y.)
| | - Long Gan
- Energy Research Institute, Jiangxi Academy of Sciences, Nanchang 330012, China;
| | - Zehui Zhang
- School of Water Resources & Environmental Engineering, East China University of Technology, Nanchang 330013, China;
| | - Shibiao Zhou
- Physical Education College, Jiangxi Normal University, Nanchang 330022, China; (X.G.); (L.Y.); (S.Z.); (Z.F.); (S.C.); (X.Z.); (H.Y.)
| | - Zhenliang Fu
- Physical Education College, Jiangxi Normal University, Nanchang 330022, China; (X.G.); (L.Y.); (S.Z.); (Z.F.); (S.C.); (X.Z.); (H.Y.)
| | - Yu Liu
- Research Institute of Microbiology, Jiangxi Academy of Sciences, Nanchang 330012, China; (Y.L.); (Z.X.)
| | - Zaijun Xin
- Research Institute of Microbiology, Jiangxi Academy of Sciences, Nanchang 330012, China; (Y.L.); (Z.X.)
| | - Shaohang Cheng
- Physical Education College, Jiangxi Normal University, Nanchang 330022, China; (X.G.); (L.Y.); (S.Z.); (Z.F.); (S.C.); (X.Z.); (H.Y.)
| | - Xinyou Zhou
- Physical Education College, Jiangxi Normal University, Nanchang 330022, China; (X.G.); (L.Y.); (S.Z.); (Z.F.); (S.C.); (X.Z.); (H.Y.)
| | - Hualong Yan
- Physical Education College, Jiangxi Normal University, Nanchang 330022, China; (X.G.); (L.Y.); (S.Z.); (Z.F.); (S.C.); (X.Z.); (H.Y.)
| | - Qiyu Wang
- Research Institute of Microbiology, Jiangxi Academy of Sciences, Nanchang 330012, China; (Y.L.); (Z.X.)
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Termite F, Archilei S, D’Ambrosio F, Petrucci L, Viceconti N, Iaccarino R, Liguori A, Gasbarrini A, Miele L. Gut Microbiota at the Crossroad of Hepatic Oxidative Stress and MASLD. Antioxidants (Basel) 2025; 14:56. [PMID: 39857390 PMCID: PMC11759774 DOI: 10.3390/antiox14010056] [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: 12/13/2024] [Revised: 12/30/2024] [Accepted: 01/02/2025] [Indexed: 01/27/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition marked by excessive lipid accumulation in hepatic tissue. This disorder can lead to a range of pathological outcomes, including metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. Despite extensive research, the molecular mechanisms driving MASLD initiation and progression remain incompletely understood. Oxidative stress and lipid peroxidation are pivotal in the "multiple parallel hit model", contributing to hepatic cell death and tissue damage. Gut microbiota plays a substantial role in modulating hepatic oxidative stress through multiple pathways: impairing the intestinal barrier, which results in bacterial translocation and chronic hepatic inflammation; modifying bile acid structure, which impacts signaling cascades involved in lipidic metabolism; influencing hepatocytes' ferroptosis, a form of programmed cell death; regulating trimethylamine N-oxide (TMAO) metabolism; and activating platelet function, both recently identified as pathogenetic factors in MASH progression. Moreover, various exogenous factors impact gut microbiota and its involvement in MASLD-related oxidative stress, such as air pollution, physical activity, cigarette smoke, alcohol, and dietary patterns. This manuscript aims to provide a state-of-the-art overview focused on the intricate interplay between gut microbiota, lipid peroxidation, and MASLD pathogenesis, offering insights into potential strategies to prevent disease progression and its associated complications.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Luca Miele
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy (S.A.)
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Kovynev A, Ying Z, Zhang S, Olgiati E, Lambooij JM, Visentin C, Guigas B, Ducarmon QR, Rensen PCN, Schönke M. Timing Matters: Late, but Not Early, Exercise Training Ameliorates MASLD in Part by Modulating the Gut-Liver Axis in Mice. J Pineal Res 2024; 76:e70003. [PMID: 39539028 DOI: 10.1111/jpi.70003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 10/10/2024] [Accepted: 10/21/2024] [Indexed: 11/16/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects two billion people worldwide and is currently mostly treatable via lifestyle interventions, such as exercise training. However, it is unclear whether the positive effects of exercise are restricted to unique circadian windows. We therefore aimed to study whether the timing of exercise training differentially modulates MASLD development. Twenty weeks old male APOE*3-Leiden.CETP mice were fed a high fat-high cholesterol diet to induce MASLD and treadmill-trained for 1 h five times per week for 12 weeks either early (ZT13; E-RUN) or late (ZT22; L-RUN) in the dark phase while corresponding sedentary groups (E-SED and L-SED) did not. Late, but not early exercise training decreased the MASLD score, body weight, fat mass, and liver triglycerides, accompanied by an altered composition of the gut microbiota. Specifically, only late exercise training increased the abundance of short-chain fatty acid-producing bacterial families and genera, such as Akkermansia, Lachnospiraceae, and Rikenella. To assess the role of the gut microbiota in training-induced effects, the study was repeated and trained (ZT22 only, RUN) or sedentary mice (SED) served as fecal donors for sedentary recipient mice (RUN FMT and SED FMT). Fecal microbiota transplantation reduced liver weight and plasma triglycerides in RUN FMT compared to SED FMT and tended to lower the MASLD score and liver triglycerides. Timing of exercise training is a critical factor for the positive effect on MASLD in this preclinical model, and the effect of late exercise is partially mediated via the gut-liver axis.
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Affiliation(s)
- Artemiy Kovynev
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Zhixiong Ying
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Sen Zhang
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Emanuele Olgiati
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Joost M Lambooij
- Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, The Netherlands
- Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands
| | - Clara Visentin
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Bruno Guigas
- Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, The Netherlands
| | - Quinten R Ducarmon
- Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, The Netherlands
| | - Patrick C N Rensen
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Milena Schönke
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Lei S, Liu G, Wang S, Zong G, Zhang X, Pan L, Han J. Intermittent Fasting Improves Insulin Resistance by Modulating the Gut Microbiota and Bile Acid Metabolism in Diet-Induced Obesity. Mol Nutr Food Res 2024; 68:e2400451. [PMID: 39520336 PMCID: PMC11605789 DOI: 10.1002/mnfr.202400451] [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: 06/18/2024] [Revised: 10/04/2024] [Indexed: 11/16/2024]
Abstract
SCOPE Adipose tissue macrophages (ATMs) are crucial in the pathogenesis of insulin resistance (IR). Intermittent fasting (IF) is an effective intervention for obesity. However, the underlying mechanism by which IF improves IR remains unclear. METHODS AND RESULTS Male C57BL/6J mice are fed chow-diet and high-fat diet (HFD) for 12 weeks, then is randomized into ad libitum feeding or every other day fasting for 8 weeks. Markers of ATMs and expression of uncoupling protein 1 (UCP-1) are determined. Gut microbiota and bile acids (BAs) are profiled using 16S rRNA sequencing and targeted metabolomics analysis. Results indicate that IF improves IR in HFD-induced obesity. IF decreases ATM infiltration, pro-inflammatory M1 gene expression, and promotes white adipose tissue (WAT) browning by elevating UCP-1 expression. IF restructures microbiota composition, significantly expanding the abundance of Verrucomicrobia particularly Akkermansia muciniphila, with the decrease of that of Firmicutes. IF increases the level of total BAs and alters the composition of BAs with higher proportion of 12α-hydroxylated (12α-OH) BAs. The changes in these BAs are correlated with differential bacteria. CONCLUSION The findings indicate that IF improves IR partially mediated by the interplay between restructured gut microbiota and BAs metabolism, which has implications for the dietary management in obesity.
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Affiliation(s)
- Sha Lei
- Department of Endocrinology and Metabolism, Tongji Hospital, School of MedicineTongji UniversityShanghai200065China
| | - Guanghui Liu
- Department of Endocrinology and Metabolism, Tongji Hospital, School of MedicineTongji UniversityShanghai200065China
| | - Shouli Wang
- Department of Hematology, Shanghai Ninth People's HospitalShanghai Jiaotong University School of MedicineShanghai200233China
| | - Guannan Zong
- Department of Endocrinology and Metabolism, Tongji Hospital, School of MedicineTongji UniversityShanghai200065China
| | - Xiaoya Zhang
- Department of Endocrinology and Metabolism, Tongji Hospital, School of MedicineTongji UniversityShanghai200065China
| | - Lingling Pan
- Department of Endocrinology and Metabolism, Tongji Hospital, School of MedicineTongji UniversityShanghai200065China
| | - Junfeng Han
- Department of Endocrinology and Metabolism, Tongji Hospital, School of MedicineTongji UniversityShanghai200065China
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Chaudhary S, Kaur P, Singh TA, Bano KS, Vyas A, Mishra AK, Singh P, Mehdi MM. The dynamic crosslinking between gut microbiota and inflammation during aging: reviewing the nutritional and hormetic approaches against dysbiosis and inflammaging. Biogerontology 2024; 26:1. [PMID: 39441393 DOI: 10.1007/s10522-024-10146-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 10/01/2024] [Indexed: 10/25/2024]
Abstract
The early-life gut microbiota (GM) is increasingly recognized for its contributions to human health and disease over time. Microbiota composition, influenced by factors like race, geography, lifestyle, and individual differences, is subject to change. The GM serves dual roles, defending against pathogens and shaping the host immune system. Disruptions in microbial composition can lead to immune dysregulation, impacting defense mechanisms. Additionally, GM aids digestion, releasing nutrients and influencing physiological systems like the liver, brain, and endocrine system through microbial metabolites. Dysbiosis disrupts intestinal homeostasis, contributing to age-related diseases. Recent studies are elucidating the bacterial species that characterize a healthy microbiota, defining what constitutes a 'healthy' colonic microbiota. The present review article focuses on the importance of microbiome composition for the development of homeostasis and the roles of GM during aging and the age-related diseases caused by the alteration in gut microbial communities. This article might also help the readers to find treatments targeting GM for the prevention of various diseases linked to it effectively.
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Affiliation(s)
- Sakshi Chaudhary
- Department of Biochemistry, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Pardeep Kaur
- Department of Biotechnology, Chandigarh University, Mohali, Punjab, 140413, India
| | - Thokchom Arjun Singh
- Department of Microbiology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Kaniz Shahar Bano
- Department of Microbiology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Ashish Vyas
- Department of Microbiology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Alok Kumar Mishra
- Department of Microbiology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Prabhakar Singh
- Department of Biotechnology, School of Bio and Chemical Engineering, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, 600119, India
| | - Mohammad Murtaza Mehdi
- Department of Biochemistry, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India.
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Okada G, Mabuchi R, Kambara C, Tanimoto S, Fujii T. Association of eating habits and Firmicutes/Bacteroidetes ratio among Japanese female university students: A cross-sectional study. Nutr Health 2024; 30:555-563. [PMID: 36177526 DOI: 10.1177/02601060221129771] [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: 11/16/2022]
Abstract
Background & Aims: University students are prone to changes in their health status and lifestyle due to changes in their living environment and associated stress and anxiety. These changes may affect them in later life. This study utilized a cross-sectional study among Japanese female university students to examine dietary factors affecting their fecal microbiota. Methods: Sixty-eight healthy female university students were evaluated using an eating behavior assessment and diet history questionnaire. The 12-component Japanese diet index (JDI-12) was then calculated. A quantitative real-time PCR method was used to analyze the predominant bacterial species in the gut, and the Firmicutes/Bacteroidetes ratio (F/B ratio) at the phylum level was calculated. The partial correlation between the fecal microbiota and eating behavior abnormality score was assessed, and dietary habits associated with the F/B ratio were analyzed. Results: A significant correlation was identified between F/B ratios and the eating behavior abnormality score (r = 0.26, FDR = 0.064). Additionally, multiple regression analysis identified a negative correlation trend between the F/B ratio and JDI-12 score (β = -0.22; p = 0.091), and exploratory analysis found a negative association between the F/B ratio and consumption of beef and pork, one of the less beneficial JDI-12 components (β = -0.33, FDR = 0.120). Conclusion: In healthy female university students, there was a positive correlation between eating behavior abnormality and the F/B ratio, indicating that adherence to the Japanese diet pattern may be associated with a lower F/B ratio.
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Affiliation(s)
- Genya Okada
- Department of Health Sciences, Prefectural University of Hiroshima, Hiroshima, Japan
| | - Ryota Mabuchi
- Department of Local Resources, Faculty of Bioresource Science, Prefectural University of Hiroshima, Hiroshima, Japan
| | - Chisako Kambara
- Department of Health Sciences, Prefectural University of Hiroshima, Hiroshima, Japan
| | - Shota Tanimoto
- Department of Health Sciences, Prefectural University of Hiroshima, Hiroshima, Japan
| | - Tamotsu Fujii
- Department of Health Sciences, Prefectural University of Hiroshima, Hiroshima, Japan
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Lange EC, Rampelotto PH, Longo L, de Freitas LBR, Uribe-Cruz C, Alvares-da-Silva MR. Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease. World J Hepatol 2024; 16:832-842. [PMID: 38818297 PMCID: PMC11135274 DOI: 10.4254/wjh.v16.i5.832] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 02/02/2024] [Accepted: 03/05/2024] [Indexed: 05/22/2024] Open
Abstract
BACKGROUND Metabolic-dysfunction associated steatotic liver disease (MASLD) is a hepatic manifestation of metabolic syndrome. Studies suggest ornithine aspartate (LOLA) as drug therapy. AIM To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD. METHODS Adult male Sprague Dawley rats were randomized into three groups: Control (10 rats fed with a standard diet), MASLD (10 rats fed with a high-fat and choline-deficient diet), and LOLA (10 rats receiving 200 mg/kg/d LOLA, after the 16th week receiving high-fat and choline-deficient diet). After 28 wk of the experiment, animals were euthanized, and feces present in the intestine were collected. Following fecal DNA extraction, the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™ system. RESULTS Alpha and beta diversity metrics were comparable between MASLD and LOLA. 3 OTUs were differentially abundant between MASLD and LOLA, which belong to the species Helicobacter rodentium, Parabacteroides goldsteinii, and Parabacteroides distasonis. The functional prediction provided two different metabolic profiles between MASLD and LOLA. The 9 pathways differentially abundant in MASLD are related to a change in energy source, adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis. The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate, including tricarboxylic acid cycle pathways, purine/guanosine nucleotides biosynthesis, pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis. CONCLUSION Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD, it was associated with changes in specific gut microbes and their related metabolic pathways.
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Affiliation(s)
- Elisa Carolina Lange
- Experimental Laboratory of Hepatology and Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-007, Brazil
| | - Pabulo Henrique Rampelotto
- Experimental Laboratory of Hepatology and Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
- Bioinformatics and Biostatistics Core Facility, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brazil
- Graduate Program in Biological Sciences: Pharmacology and Therapeutics, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-007, Brazil
| | - Larisse Longo
- Experimental Laboratory of Hepatology and Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-007, Brazil
| | - Laura Bainy Rodrigues de Freitas
- Experimental Laboratory of Hepatology and Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
| | - Carolina Uribe-Cruz
- Experimental Laboratory of Hepatology and Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-007, Brazil
- Facultad de Ciencias de la Salud, Universidad Católica de las Misiones, Posadas, Misiones 3300, Argentina
| | - Mario Reis Alvares-da-Silva
- Experimental Laboratory of Hepatology and Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-007, Brazil
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, RS, Brazil
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) researcher, Brasília 71605-001, Brazil.
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9
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Tsigalou C, Tsolou A, Stavropoulou E, Konstantinidis T, Zafiriou E, Dardiotis E, Tsirogianni A, Bogdanos D. Unraveling the intricate dance of the Mediterranean diet and gut microbiota in autoimmune resilience. Front Nutr 2024; 11:1383040. [PMID: 38818135 PMCID: PMC11137302 DOI: 10.3389/fnut.2024.1383040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 05/07/2024] [Indexed: 06/01/2024] Open
Abstract
The nutritional habits regulate the gut microbiota and increase risk of an autoimmune disease. Western diet is rich in sugars, meat, and poly-unsaturated fatty acids, which lead to dysbiosis of intestinal microbiota, disruption of gut epithelial barrier and chronic mucosal inflammation. In contrast, the Mediterranean Diet (MedDiet) is abundant in ω3 fatty acids, fruits, and vegetables, possessing anti-inflammatory properties that contribute to the restoration of gut eubiosis. Numerous studies have extensively examined the impact of MedDiet and its components on both health and various disease states. Additionally, specific investigations have explored the correlation between MedDiet, microbiota, and the risk of autoimmune diseases. Furthermore, the MedDiet has been linked to a reduced risk of cardiovascular diseases, playing a pivotal role in lowering mortality rates among individuals with autoimmune diseases and comorbidities. The aim of the present review is to specifically highlight current knowledge regarding possible interactions of MedDiet with the patterns of intestinal microbiota focusing on autoimmunity and a blueprint through dietary modulations for the prevention and management of disease's activity and progression.
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Affiliation(s)
- Christina Tsigalou
- Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, University Hospital, Alexandroupolis, Greece
| | - Avgi Tsolou
- Laboratory of Molecular Cell Biology, Cell Cycle and Proteomics, Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece
| | - Elisavet Stavropoulou
- Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, University Hospital, Alexandroupolis, Greece
| | - Theocharis Konstantinidis
- Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, University Hospital, Alexandroupolis, Greece
| | - Efterpi Zafiriou
- Department of Dermatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
| | - Efthymios Dardiotis
- Department of Neurology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
| | - Alexandra Tsirogianni
- Department of Immunology-Histocompatibility, Evangelismos General Hospital, Athens, Greece
| | - Dimitrios Bogdanos
- Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
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10
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Sia T, Tanaka RO, Mousad A, Narayan AP, Si K, Bacchus L, Ouerghi H, Patel A, Patel A, Cunningham E, Epstein T, Fu J, Liu S, Khuda R, McDonald P, Mallik S, McNulty J, Pan M, Leung J. Fructose malabsorption and fructan malabsorption are associated in patients with irritable bowel syndrome. BMC Gastroenterol 2024; 24:143. [PMID: 38654193 PMCID: PMC11040878 DOI: 10.1186/s12876-024-03230-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 04/15/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND Food malabsorption and intolerance is implicated in gastrointestinal symptoms among patients with irritable bowel syndrome (IBS). Key triggers include fructose and fructan. Prior studies examined fructose and fructan malabsorption separately in IBS patients. None have concurrently assessed both within the same patient group. We aimed to investigate the association between fructose and fructan malabsorption in the same patients with IBS using hydrogen breath testing (HBT). METHODS We retrospectively identified patients with IBS who underwent fructose and fructan HBTs and abstracted their results from the electronic medical record. Fructose and fructan HBTs were performed by administering a 25 g fructose solution or 10 g fructan solution, followed by breath hydrogen readings every 30 min for 3 h. Patients were positive for fructose or fructan malabsorption if breath hydrogen levels exceeded 20 ppm. RESULTS Of 186 IBS patients, 71 (38.2%) were positive for fructose malabsorption and 91 (48.9%) were positive for fructan malabsorption. Of these patients, 42 (22.6%) were positive for fructose malabsorption and fructan malabsorption. Positive fructose HBT readings were significantly associated with positive fructan HBT readings (p = 0.0283). Patients positive for fructose malabsorption or fructan malabsorption had 1.951 times higher odds of testing positive for the other carbohydrate. CONCLUSIONS Our results reveal a clinically significant association between fructose malabsorption and fructan malabsorption in patients with IBS. Fructan malabsorption should be assessed in patients with fructose malabsorption, and vice versa. Further studies are required to identify the mechanisms underlying our findings.
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Affiliation(s)
- Twan Sia
- Boston Specialists, 65 Harrison Ave #201, Boston, MA, 02111, USA
- Stanford University School of Medicine, 291 Campus Drive, Stanford, CA, 94305, USA
| | - Riki O Tanaka
- Boston Specialists, 65 Harrison Ave #201, Boston, MA, 02111, USA
| | - Albert Mousad
- Tufts University School of Medicine, 145 Harrison Ave, Boston, MA, 02111, USA
| | - Aditya P Narayan
- Stanford University School of Medicine, 291 Campus Drive, Stanford, CA, 94305, USA
| | - Kristen Si
- Boston Specialists, 65 Harrison Ave #201, Boston, MA, 02111, USA
| | - Leeon Bacchus
- Boston Specialists, 65 Harrison Ave #201, Boston, MA, 02111, USA
| | - Hind Ouerghi
- Boston Specialists, 65 Harrison Ave #201, Boston, MA, 02111, USA
| | - Aashka Patel
- Boston Specialists, 65 Harrison Ave #201, Boston, MA, 02111, USA
| | - Arnav Patel
- Boston Specialists, 65 Harrison Ave #201, Boston, MA, 02111, USA
| | - Evan Cunningham
- Boston Specialists, 65 Harrison Ave #201, Boston, MA, 02111, USA
| | - Taylor Epstein
- Boston Specialists, 65 Harrison Ave #201, Boston, MA, 02111, USA
| | - Jerry Fu
- Boston Specialists, 65 Harrison Ave #201, Boston, MA, 02111, USA
| | - Stanley Liu
- Boston Specialists, 65 Harrison Ave #201, Boston, MA, 02111, USA
| | - Raisa Khuda
- Boston Specialists, 65 Harrison Ave #201, Boston, MA, 02111, USA
| | - Paige McDonald
- Boston Specialists, 65 Harrison Ave #201, Boston, MA, 02111, USA
| | - Shibani Mallik
- Boston Specialists, 65 Harrison Ave #201, Boston, MA, 02111, USA
| | - Joanna McNulty
- Boston Specialists, 65 Harrison Ave #201, Boston, MA, 02111, USA
| | - Michelle Pan
- Boston Specialists, 65 Harrison Ave #201, Boston, MA, 02111, USA
| | - John Leung
- Boston Specialists, 65 Harrison Ave #201, Boston, MA, 02111, USA.
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11
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Zhou X, Zhang J, Sun Y, Shen J, Sun B, Ma Q. Glutamine Ameliorates Liver Steatosis via Regulation of Glycolipid Metabolism and Gut Microbiota in High-Fat Diet-Induced Obese Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:15656-15667. [PMID: 37847053 DOI: 10.1021/acs.jafc.3c05566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2023]
Abstract
Obesity and its associated conditions, such as nonalcoholic fatty liver disease (NAFLD), are risk factors for health. The aim of this study was to explore the effects of glutamine (Gln) on liver steatosis induced by a high-fat diet (HFD) and HEPG2 cells induced by oleic acid. Gln demonstrated a positive influence on hepatic homeostasis by suppressing acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS) and promoting sirtuin 1 (SIRT1) expression while improving glucose metabolism by regulating serine/threonine protein kinase (AKT)/factor forkhead box O1 (FOXO1) signals in vivo and in vitro. Obese Gln-fed mice had higher colonic short-chain fatty acid (SCFA) contents and lower inflammation factor protein levels in the liver, HEPG2 cells, and jejunum. Gln-treated obese mice had an effective decrease in Firmicutes abundance. These findings indicate that Gln serves as a nutritional tool in managing obesity and related disorders.
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Affiliation(s)
- Xinbo Zhou
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
| | - Junjie Zhang
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
| | - Yutong Sun
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
| | - Jian Shen
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
| | - Bo Sun
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
| | - Qingquan Ma
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
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12
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Zhao Y, Li C, Luan Z, Chen J, Wang C, Jing Y, Qi S, Zhao Z, Zhang H, Wu J, Chen Y, Li Z, Zhao B, Wang S, Yang Y, Sun G. Lactobacillus oris improves non-alcoholic fatty liver in mice and inhibits endogenous cholesterol biosynthesis. Sci Rep 2023; 13:12946. [PMID: 37558739 PMCID: PMC10412569 DOI: 10.1038/s41598-023-38530-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: 09/01/2022] [Accepted: 07/10/2023] [Indexed: 08/11/2023] Open
Abstract
We previously confirmed that a strain of Lactobacillus oris isolated from the fecal samples of healthy Hainan centenarian having potent lipid-lowering ability in HepG2 cells; and this study was to investigate the effect of the stain on non-alcoholic fatty liver in mice in vivio. The Lactobacillus oris strain isolated from Hainan centenarian fecal samples were frozen stored in our laboratory. Thirty ob/ob mice (10 in each group) were orally gavaged with Lactobacillus oris (Lactobacillus, 5 × 109 cfu), mixed probiotics (Mixed, 5 × 109 cfu, a mixture with known lipid-lowering ability), or culture medium (Control) respectively. Lactobacillus oris isolated from fecal samples of Hainan centenarians showed significantly in vivo lipid lowering ability compared with the controls, and the ability was comparable with mixed probiotics strains in mice The possible mechanisms of lipid-lowering of probiotics and Lactobacillus oris may be associated with HMGR inhibition to suppress the synthesis of endogenous cholesterol; bile acids reabsorption, and intestinal FXR-FGF15 signaling pathways promoting the cholesterol conversion into bile acids secretion.
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Affiliation(s)
- Yiming Zhao
- Department of Gastroenterology and Hepatology, Hainan Hospital of PLA General Hospital, Sanya, 572013, China
| | - Congyong Li
- Sixth Health Care Department, Second Medical Center of PLA General Hospital, Beijing, 100853, China
| | - Zhe Luan
- Department of Gastroenterology and Hepatology, First Medical Center of PLA General Hospital, Beijing, 100853, China
| | - Jun Chen
- Unit 91917, Beijing, 102401, China
| | - Cong Wang
- Emergency Department, Tianjin First Central Hospital, Tianjin, 300192, China
| | - Yujia Jing
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China
| | - Shirui Qi
- Emergency Department, Tianjin First Central Hospital, Tianjin, 300192, China
| | - Zhizhuang Zhao
- Department of Gastroenterology and Hepatology, Hainan Hospital of PLA General Hospital, Sanya, 572013, China
| | - Hanwen Zhang
- Department of Gastroenterology and Hepatology, First Medical Center of PLA General Hospital, Beijing, 100853, China
| | - Junling Wu
- Department of Gastroenterology and Hepatology, First Medical Center of PLA General Hospital, Beijing, 100853, China
| | - Yi Chen
- Department of Gastroenterology and Hepatology, First Medical Center of PLA General Hospital, Beijing, 100853, China
| | - Zhuanyu Li
- Beijing QuantiHealth Technology Co., Ltd., Beijing, 100070, China
| | - Bowen Zhao
- Beijing QuantiHealth Technology Co., Ltd., Beijing, 100070, China
| | - Shufang Wang
- Department of Gastroenterology and Hepatology, First Medical Center of PLA General Hospital, Beijing, 100853, China.
| | - Yunsheng Yang
- Department of Gastroenterology and Hepatology, First Medical Center of PLA General Hospital, Beijing, 100853, China.
| | - Gang Sun
- Department of Gastroenterology and Hepatology, First Medical Center of PLA General Hospital, Beijing, 100853, China.
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13
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Wang L, Jiang Y, Yu Q, Xiao C, Sun J, Weng L, Qiu Y. Gentiopicroside improves high-fat diet-induced NAFLD in association with modulation of host serum metabolome and gut microbiome in mice. Front Microbiol 2023; 14:1145430. [PMID: 37614606 PMCID: PMC10443917 DOI: 10.3389/fmicb.2023.1145430] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 07/24/2023] [Indexed: 08/25/2023] Open
Abstract
Objective The incidence of non-alcoholic fatty liver disease is increasing every year, and there is growing evidence that metabolites and intestinal bacteria play a causal role in NAFLD. Gentiopicroside, a major iridoids compound in gentian, has been reported to reduce hepatic lipid accumulation. However to date, no studies have confirmed whether the predominance of Gentiopicroside is related to metabolites and intestinal bacteria. Therefore, we sought to study whether the hypolipidemic effect of Gentiopicroside is related to metabolic function and intestinal flora regulation. Methods In the present study, C57BL/6J mice were fed a high-fat diet for 12 weeks, followed by a high-fat diet with or without Gentiopicroside for 8 weeks, respectively. The Gentiopicroside intervention reduced body weight gain, liver index, and decreased serum biochemical parameters such as alanine aminotransferase, aspartate aminotransferase, and triglycerides in high-fat fed mice. The effect of Gentiopicroside on non-alcoholic fatty liver disease was studied using serum untargeted metabolomics and 16S rDNA assay. Results Metabolomic analysis showed that the addition of Gentiopicroside significantly altered the levels of amino acids, unmetabolized Gentiopicroside after administration, and metabolites such as Cinnoline, Galabiosylceramide, and Tryptophyl-Tyrosine, which are involved in the pathways regulating bile secretion, tryptophan metabolism, and lipid metabolism. Analysis of intestinal bacteria showed that Gentiopicrosides altered the community composition structure of intestinal bacteria, characterized by an increase and a decrease in beneficial and harmful bacteria, respectively. In addition, correlation analysis showed that the effect of Gentiopicroside on metabolites was positively correlated with intestinal flora Bacteroides, Lactobacillus, Muribaculum, and Prevotellaceae_UCG_001. Finally, the combined analysis revealed that metabolites were associated with the regulation of Firmicutes and Actinobacteria and positively correlated with lipid levels. Conclusion These results suggest that Gentiopicroside may be a potential agent for the prevention of intestinal disorders and the alleviation of non-alcoholic fatty liver disease.
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Affiliation(s)
| | | | | | | | | | - Lili Weng
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Ye Qiu
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
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14
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Sun E, Meng X, Kang Z, Gu H, Li M, Tan X, Feng L, Jia X. Zengshengping improves lung cancer by regulating the intestinal barrier and intestinal microbiota. Front Pharmacol 2023; 14:1123819. [PMID: 36992837 PMCID: PMC10040556 DOI: 10.3389/fphar.2023.1123819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 02/24/2023] [Indexed: 03/16/2023] Open
Abstract
Lung cancer is a common malignant tumor in clinical practice, and its morbidity and mortality are in the forefront of malignant tumors. Radiotherapy, chemotherapy, and surgical treatment play an important role in the treatment of lung cancer, however, radiotherapy has many complications and even causes partial loss of function, the recurrence rate after surgical resection is high, and the toxic and side effects of chemotherapy drugs are strong. Traditional Chinese medicine has played a huge role in the prognosis and improvement of lung cancer, among them, Zengshengping (ZSP) has the effect of preventing and treating lung cancer. Based on the “gut-lung axis” and from the perspective of “treating the lung from the intestine”, the purpose of this study was to research the effect of Zengshengping on the intestinal physical, biological, and immune barriers, and explore its role in the prevention and treatment of lung cancer. The Lewis lung cancer and urethane-induced lung cancer models were established in C57BL/6 mice. The tumor, spleen, and thymus were weighed, and the inhibition rate, splenic and thymus indexes analyzed. Inflammatory factors and immunological indexes were detected by enzyme-linked immunosorbent assay. Collecting lung and colon tissues, hematoxylin and eosin staining was performed on lung, colon tissues to observe histopathological damage. Immunohistochemistry and Western blotting were carried out to detect tight junction protein expression in colon tissues and expression of Ki67 and p53 proteins in tumor tissues. Finally, the feces of mice were collected to investigate the changes in intestinal microbiota using 16SrDNA high-throughput sequencing technology. ZSP significantly reduced tumor weight and increased the splenic and thymus indexes. It decreased expression of Ki67 protein and increased expression of p53 protein. Compared with Model group, ZSP group reduced the serum levels of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α), and ZSP group increased the concentration of secretory immunoglobulin A (sIgA) in the colon and the bronchoalveolar lavage fluid (BALF). ZSPH significantly increased the level of tight junction proteins such as ZO-1, Occludin and Claudin-1. Model group significantly reduced the relative abundance of Akkermansia (p < 0.05) and significantly promoted the amount of norank_f_Muribaculaceae, norank_f_Lachnospiraceae (p < 0.05) compared with that in the Normal group. However, ZSP groups increased in probiotic strains (Akkermansia) and decreased in pathogens (norank_f_Muribaculaceae, norank_f_Lachnospiraceae). Compared with the urethane-induced lung cancer mice, the results showed that ZSP significantly increased the diversity and richness of the intestinal microbiota in the Lewis lung cancer mice. ZSP played an important role in the prevention and treatment of lung cancer by enhancing immunity, protecting the intestinal mucosa and regulating the intestinal microbiota.
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Affiliation(s)
- E. Sun
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- Key Laboratory of New Drug Delivery System of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, China
| | - Xiangqi Meng
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- Key Laboratory of New Drug Delivery System of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, China
| | - Zhaoxia Kang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- Key Laboratory of New Drug Delivery System of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, China
| | - Huimin Gu
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Mingyu Li
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiaobin Tan
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- Key Laboratory of New Drug Delivery System of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, China
| | - Liang Feng
- School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
- *Correspondence: Liang Feng, ; Xiaobin Jia,
| | - Xiaobin Jia
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
- *Correspondence: Liang Feng, ; Xiaobin Jia,
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15
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Guimarães VHD, Marinho BM, Motta-Santos D, Mendes GDRL, Santos SHS. Nutritional implications in the mechanistic link between the intestinal microbiome, renin-angiotensin system, and the development of obesity and metabolic syndrome. J Nutr Biochem 2023; 113:109252. [PMID: 36509338 DOI: 10.1016/j.jnutbio.2022.109252] [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: 06/10/2022] [Revised: 11/12/2022] [Accepted: 12/07/2022] [Indexed: 12/13/2022]
Abstract
Obesity and metabolic disorders represent a significant global health problem and the gut microbiota plays an important role in modulating systemic homeostasis. Recent evidence shows that microbiota and its signaling pathways may affect the whole metabolism and the Renin-Angiotensin System (RAS), which in turn seems to modify microbiota. The present review aimed to investigate nutritional implications in the mechanistic link between the intestinal microbiome, renin-angiotensin system, and the development of obesity and metabolic syndrome components. A description of metabolic changes was obtained based on relevant scientific literature. The molecular and physiological mechanisms that impact the human microbiome were addressed, including the gut microbiota associated with obesity, diabetes, and hepatic steatosis. The RAS interaction signaling and modulation were analyzed. Strategies including the use of prebiotics, symbiotics, probiotics, and biotechnology may affect the gut microbiota and its impact on human health.
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Affiliation(s)
- Victor Hugo Dantas Guimarães
- Laboratory of Health Science, Postgraduate Program in Health Science, Universidade Estadual de Montes Claros (Unimontes), Montes Claros, Minas Gerais, Brazil
| | - Barbhara Mota Marinho
- Laboratory of Health Science, Postgraduate Program in Health Science, Universidade Estadual de Montes Claros (Unimontes), Montes Claros, Minas Gerais, Brazil
| | - Daisy Motta-Santos
- School of Physical Education, Physiotherapy, and Occupational Therapy - EEFFTO, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil
| | - Gabriela da Rocha Lemos Mendes
- Food Engineering, Institute of Agricultural Sciences (ICA), Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil
| | - Sérgio Henrique Sousa Santos
- Laboratory of Health Science, Postgraduate Program in Health Science, Universidade Estadual de Montes Claros (Unimontes), Montes Claros, Minas Gerais, Brazil; Food Engineering, Institute of Agricultural Sciences (ICA), Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil.
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16
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Swallah MS, Bondzie-Quaye P, Wu Y, Acheampong A, Sossah FL, Elsherbiny SM, Huang Q. Therapeutic potential and nutritional significance of Ganoderma lucidum - a comprehensive review from 2010 to 2022. Food Funct 2023; 14:1812-1838. [PMID: 36734035 DOI: 10.1039/d2fo01683d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
With a long history in traditional Asian medicine, Ganoderma lucidum (G. lucidum) is a mushroom species suggested to improve health and extend life. Its medicinal reputation has merited it with numerous attributes and titles, and it is evidenced to be effective in the prevention and treatment of various metabolic disorders owing to its unique source of bioactive metabolites, primarily polysaccharides, triterpenoids, and polyphenols, attributed with antioxidant, anti-inflammatory, anticancer, hepatoprotective, antidiabetic activities, etc. These unique potential pharmaceutical properties have led to its demand as an important resource of nutrient supplements in the food industry. It is reported that the variety of therapeutic/pharmacological properties was mainly due to its extensive prebiotic and immunomodulatory functions. All literature summarized in this study was collated based on a systematic review of electronic libraries (PubMed, Scopus databases, Web of Science Core Collection, and Google Scholar) from 2010-2022. This review presents an updated and comprehensive summary of the studies on the immunomodulatory therapies and nutritional significance of G. lucidum, with the focus on recent advances in defining its immunobiological mechanisms and the possible applications in the food and pharmaceutical industries for the prevention and management of chronic diseases. In addition, toxicological evidence and the adoption of standard pharmaceutical methods for the safety assessment, quality assurance, and efficacy testing of G. lucidum-derived compounds will be the gateway to bringing them into health establishments.
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Affiliation(s)
- Mohammed Sharif Swallah
- CAS Key Laboratory of High Magnetic Field and Iron Beam Physical Biology, Institute of Intelligent Agriculture, Institute of Intelligent Machines, Hefei Institute of Physical Sciences, Chinese Academy of Sciences, Hefei, 230031, China. .,Science Island Branch of Graduate School, University of Science and Technology of China, Hefei, 230026, China
| | - Precious Bondzie-Quaye
- CAS Key Laboratory of High Magnetic Field and Iron Beam Physical Biology, Institute of Intelligent Agriculture, Institute of Intelligent Machines, Hefei Institute of Physical Sciences, Chinese Academy of Sciences, Hefei, 230031, China. .,Science Island Branch of Graduate School, University of Science and Technology of China, Hefei, 230026, China
| | - Yahui Wu
- CAS Key Laboratory of High Magnetic Field and Iron Beam Physical Biology, Institute of Intelligent Agriculture, Institute of Intelligent Machines, Hefei Institute of Physical Sciences, Chinese Academy of Sciences, Hefei, 230031, China. .,Science Island Branch of Graduate School, University of Science and Technology of China, Hefei, 230026, China
| | - Adolf Acheampong
- CAS Key Laboratory of High Magnetic Field and Iron Beam Physical Biology, Institute of Intelligent Agriculture, Institute of Intelligent Machines, Hefei Institute of Physical Sciences, Chinese Academy of Sciences, Hefei, 230031, China. .,Science Island Branch of Graduate School, University of Science and Technology of China, Hefei, 230026, China
| | - Frederick Leo Sossah
- Council For Scientific And Industrial Research (CSIR), Oil Palm Research Institute, Coconut Research Programme, P.O.Box 245, Sekondi, Ghana.,Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, China
| | - Shereen M Elsherbiny
- CAS Key Laboratory of High Magnetic Field and Iron Beam Physical Biology, Institute of Intelligent Agriculture, Institute of Intelligent Machines, Hefei Institute of Physical Sciences, Chinese Academy of Sciences, Hefei, 230031, China. .,Science Island Branch of Graduate School, University of Science and Technology of China, Hefei, 230026, China.,Department of Physics, Faculty of Science, Mansoura University, Mansoura 33516, Egypt
| | - Qing Huang
- CAS Key Laboratory of High Magnetic Field and Iron Beam Physical Biology, Institute of Intelligent Agriculture, Institute of Intelligent Machines, Hefei Institute of Physical Sciences, Chinese Academy of Sciences, Hefei, 230031, China. .,Science Island Branch of Graduate School, University of Science and Technology of China, Hefei, 230026, China
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17
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Non-alcoholic Fatty Liver Disease (NAFLD), Type 2 Diabetes, and Non-viral Hepatocarcinoma: Pathophysiological Mechanisms and New Therapeutic Strategies. Biomedicines 2023; 11:biomedicines11020468. [PMID: 36831004 PMCID: PMC9953066 DOI: 10.3390/biomedicines11020468] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 02/01/2023] [Accepted: 02/03/2023] [Indexed: 02/09/2023] Open
Abstract
In recent years, the incidence of non-viral hepatocellular carcinoma (HCC) has increased dramatically, which is probably related to the increased prevalence of metabolic syndrome, together with obesity and type 2 diabetes mellitus (T2DM). Several epidemiological studies have established the association between T2DM and the incidence of HCC and have demonstrated the role of diabetes mellitus as an independent risk factor for the development of HCC. The pathophysiological mechanisms underlying the development of Non-alcoholic fatty liver disease (NAFLD) and its progression to Non-alcoholic steatohepatitis (NASH) and cirrhosis are various and involve pro-inflammatory agents, oxidative stress, apoptosis, adipokines, JNK-1 activation, increased IGF-1 activity, immunomodulation, and alteration of the gut microbiota. Moreover, these mechanisms are thought to play a significant role in the development of NAFLD-related hepatocellular carcinoma. Early diagnosis and the timely correction of risk factors are essential to prevent the onset of liver fibrosis and HCC. The purpose of this review is to summarize the current evidence on the association among obesity, NASH/NAFLD, T2DM, and HCC, with an emphasis on clinical impact. In addition, we will examine the main mechanisms underlying this complex relationship, and the promising strategies that have recently emerged for these diseases' treatments.
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Ramos-Lopez O. Multi-Omics Nutritional Approaches Targeting Metabolic-Associated Fatty Liver Disease. Genes (Basel) 2022; 13:2142. [PMID: 36421817 PMCID: PMC9690481 DOI: 10.3390/genes13112142] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 11/15/2022] [Accepted: 11/16/2022] [Indexed: 10/29/2023] Open
Abstract
Currently, metabolic-associated fatty liver disease (MAFLD) is a leading global cause of chronic liver disease, and is expected to become one of the most common indications of liver transplantation. MAFLD is associated with obesity, involving multiple mechanisms such as alterations in lipid metabolism, insulin resistance, hyperinflammation, mitochondrial dysfunction, cell apoptosis, oxidative stress, and extracellular matrix formation. However, the onset and progression of MAFLD is variable among individuals, being influenced by intrinsic (personal) and external environmental factors. In this context, sequence structural variants across the human genome, epigenetic phenomena (i.e., DNA methylation, histone modifications, and long non-coding RNAs) affecting gene expression, gut microbiota dysbiosis, and metabolomics/lipidomic fingerprints may account for differences in MAFLD outcomes through interactions with nutritional features. This knowledge may contribute to gaining a deeper understanding of the molecular and physiological processes underlying MAFLD pathogenesis and phenotype heterogeneity, as well as facilitating the identification of biomarkers of disease progression and therapeutic targets for the implementation of tailored nutritional strategies. This comprehensive literature review highlights the potential of nutrigenetic, nutriepigenetic, nutrimetagenomic, nutritranscriptomics, and nutrimetabolomic approaches for the prevention and management of MAFLD in humans through the lens of precision nutrition.
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Affiliation(s)
- Omar Ramos-Lopez
- Medicine and Psychology School, Autonomous University of Baja California, Tijuana 22390, Mexico
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Microbiota Dysbiosis and Gut Barrier Dysfunction Associated with Non-Alcoholic Fatty Liver Disease Are Modulated by a Specific Metabolic Cofactors' Combination. Int J Mol Sci 2022; 23:ijms232213675. [PMID: 36430154 PMCID: PMC9692973 DOI: 10.3390/ijms232213675] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 10/31/2022] [Accepted: 11/04/2022] [Indexed: 11/10/2022] Open
Abstract
The gut is a selective barrier that not only allows the translocation of nutrients from food, but also microbe-derived metabolites to the systemic circulation that flows through the liver. Microbiota dysbiosis occurs when energy imbalances appear due to an unhealthy diet and a sedentary lifestyle. Dysbiosis has a critical impact on increasing intestinal permeability and epithelial barrier deterioration, contributing to bacterial and antigen translocation to the liver, triggering non-alcoholic fatty liver disease (NAFLD) progression. In this study, the potential therapeutic/beneficial effects of a combination of metabolic cofactors (a multi-ingredient; MI) (betaine, N-acetylcysteine, L-carnitine, and nicotinamide riboside) against NAFLD were evaluated. In addition, we investigated the effects of this metabolic cofactors' combination as a modulator of other players of the gut-liver axis during the disease, including gut barrier dysfunction and microbiota dysbiosis. Diet-induced NAFLD mice were distributed into two groups, treated with the vehicle (NAFLD group) or with a combination of metabolic cofactors (NAFLD-MI group), and small intestines were harvested from all animals for histological, molecular, and omics analysis. The MI treatment ameliorated gut morphological changes, decreased gut barrier permeability, and reduced gene expression of some proinflammatory cytokines. Moreover, epithelial cell proliferation and the number of goblet cells were increased after MI supplementation. In addition, supplementation with the MI combination promoted changes in the intestinal microbiota composition and diversity, as well as modulating short-chain fatty acids (SCFAs) concentrations in feces. Taken together, this specific combination of metabolic cofactors can reverse gut barrier disruption and microbiota dysbiosis contributing to the amelioration of NAFLD progression by modulating key players of the gut-liver axis.
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Alrahawy M, Javed S, Atif H, Elsanhoury K, Mekhaeil K, Eskander G. Microbiome and Colorectal Cancer Management. Cureus 2022; 14:e30720. [DOI: 10.7759/cureus.30720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/26/2022] [Indexed: 11/06/2022] Open
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Zhu X, Zhang Z, Yang X, Qi L, Guo Y, Tang X, Xie Y, Chen D. RETRACTED: Improvement of extraction from Hericium erinaceus on the gut-brain axis in AD-like mice. Brain Res 2022; 1793:148038. [PMID: 35934088 DOI: 10.1016/j.brainres.2022.148038] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 06/21/2022] [Accepted: 07/30/2022] [Indexed: 12/20/2022]
Abstract
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the lead author, Dr. Diling Chen. Dr. Chen alerted the Editor-in-Chief that data previously published in Aging (Albany NY). 2020 Jan 6; 12:260-287 https://doi.org/10.18632/aging.102614 were accidently reused in the above-referenced Brain Research article. Dr. Chen is a co-author on both articles. The reused content pertains to the fecal transplantation data of the model group, represented by Figure 2 in the Aging article and Figure 5 in the Brain Research article. Dr. Chen did not carefully check the data published by the team before the final submission, resulting in repeated use. The lead author states further that it was an honest mistake, and the team had no intention to plagiarize previously published material. All authors were notified and all are in agreement with the retraction. The authors apologize to the scientific community for any inconvenience or challenges resulting from the publication and retraction of this article.
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Affiliation(s)
- Xiangxiang Zhu
- Academy of Life Sciences, Jinan University, Guangdong Province, Guangzhou 510000, China; State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China
| | - Zilei Zhang
- Academy of Life Sciences, Jinan University, Guangdong Province, Guangzhou 510000, China
| | - Xin Yang
- The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, China
| | - Longkai Qi
- State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China
| | - Yinrui Guo
- State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China
| | - Xiaocui Tang
- State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China; Guangzhou Laboratory, No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou 510005, Guangdong Province, China
| | - Yizhen Xie
- State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China
| | - Diling Chen
- State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China; Guangzhou Laboratory, No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou 510005, Guangdong Province, China.
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Derosa G, Guasti L, D’Angelo A, Martinotti C, Valentino MC, Di Matteo S, Bruno GM, Maresca AM, Gaudio GV, Maffioli P. Probiotic Therapy With VSL#3® in Patients With NAFLD: A Randomized Clinical Trial. Front Nutr 2022; 9:846873. [PMID: 35685888 PMCID: PMC9172906 DOI: 10.3389/fnut.2022.846873] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Accepted: 03/07/2022] [Indexed: 12/12/2022] Open
Abstract
Aim To evaluate if VSL#3® [a high-concentration multi-strain probiotic mix containing one strain of Streptococcus thermophilus BT01, three strains of Bifidobacteria (B. breve BB02; B. animalis subspecies [subsp.] lactis BL03, previously identified as B. longum BL03; and B. animalis subsp. lactis BI04, previously identified as B. infantis BI04), and four strains of Lactobacilli (L. acidophilus BA05, L. plantarum BP06, L. paracasei BP07, and L. helveticus BD08, previously identified as L. delbrueckii subsp. bulgaricus BD08)] therapy could improve hepatic parameters. Methods We enrolled 60 Caucasian patients aged ≥ 18 years of either sex with the diagnosis of non-alcoholic fatty liver disease (NAFLD), according to practice guidance, in a double-blind, placebo-controlled study. Patients were randomized to take placebo or VSL#3®, 2 sachets/day in the morning for 3 months. VSL#3® and placebo were self-administered. Results We did not observe any change in body mass index (BMI), circumferences, fasting plasma glucose (FPG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and adiponectin (ADN) with neither treatment. A statistically significant triglycerides (Tg) decrease (p < 0.05 vs. baseline, and p < 0.05 vs. placebo, respectively) and high-sensitivity C-reactive protein (Hs-CRP) decrease (p < 0.05 vs. baseline) was observed in the group of patients being treated with VSL#3® compared with placebo. Transaminases and gamma-glutamyltransferase (γ-GT) were significantly reduced in VSL#3® group (p < 0.05 vs. baseline and placebo, respectively) compared with the placebo group. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and hepatic steatosis index (HSI) were significantly lower than the VSL#3® group (p < 0.05 vs. baseline and placebo, respectively) compared with the placebo group. All patients reported an improvement or the disappearance of hepatic steatosis. Conclusion Probiotic therapy with VSL#3® ameliorates hepatic parameters and echography grading, while reducing Tg and the inflammatory status, without any difference between men and women.
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Affiliation(s)
- Giuseppe Derosa
- Center of Diabetes and Metabolic Diseases, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Italian Nutraceutical Society (SINut), Bologna, Italy
- *Correspondence: Giuseppe Derosa,
| | - Luigina Guasti
- Geriatric Division, ASST dei Sette Laghi, University of Insubria, Varese, Italy
| | - Angela D’Angelo
- Center of Diabetes and Metabolic Diseases, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
| | - Chiara Martinotti
- S.A.V.E. Studi Analisi Valutazioni Economiche Research Center, Milan, Italy
| | | | - Sergio Di Matteo
- S.A.V.E. Studi Analisi Valutazioni Economiche Research Center, Milan, Italy
| | - Giacomo M. Bruno
- Department of Management Information and Production Engineering, University of Bergamo, Bergamo, Italy
| | - Andrea M. Maresca
- Medical Division, ASST dei Sette Laghi, University of Insubria, Varese, Italy
| | | | - Pamela Maffioli
- Center of Diabetes and Metabolic Diseases, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Italian Nutraceutical Society (SINut), Bologna, Italy
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Smirne C, Croce E, Di Benedetto D, Cantaluppi V, Comi C, Sainaghi PP, Minisini R, Grossini E, Pirisi M. Oxidative Stress in Non-Alcoholic Fatty Liver Disease. LIVERS 2022; 2:30-76. [DOI: 10.3390/livers2010003] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it still remains an orphan of adequate therapies. This review highlights the interaction between oxidative stress (OS) and disturbed lipid metabolism. Several reactive oxygen species generators, including those produced in the gastrointestinal tract, contribute to the lipotoxic hepatic (and extrahepatic) damage by fatty acids and a great variety of their biologically active metabolites in a “multiple parallel-hit model”. This leads to inflammation and fibrogenesis and contributes to NAFLD progression. The alterations of the oxidant/antioxidant balance affect also metabolism-related organelles, leading to lipid peroxidation, mitochondrial dysfunction, and endoplasmic reticulum stress. This OS-induced damage is at least partially counteracted by the physiological antioxidant response. Therefore, modulation of this defense system emerges as an interesting target to prevent NAFLD development and progression. For instance, probiotics, prebiotics, diet, and fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. The OS and its counter-regulation are under the influence of individual genetic and epigenetic factors as well. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors, coupled with new OS biomarkers, will likely assist in noninvasive diagnosis and monitoring of NAFLD progression and in further personalizing treatments.
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Affiliation(s)
- Carlo Smirne
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Eleonora Croce
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Davide Di Benedetto
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Vincenzo Cantaluppi
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Cristoforo Comi
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Pier Paolo Sainaghi
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Rosalba Minisini
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Elena Grossini
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Mario Pirisi
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
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Chaudhry R, Bamola VD, Kapardar R, Lal B, Sharma A. A metagenomic assessment of gut microbiota in Indian colon cancer patients. J Cancer Res Ther 2022; 18:96-102. [DOI: 10.4103/0973-1482.341139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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Li Y, Shao L, Mou Y, Zhang Y, Ping Y. Sleep, circadian rhythm and gut microbiota: alterations in Alzheimer's disease and their potential links in the pathogenesis. Gut Microbes 2021; 13:1957407. [PMID: 34520319 PMCID: PMC8463034 DOI: 10.1080/19490976.2021.1957407] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [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
ABSTRATCIn recent years, emerging studies have observed gut microbiota (GM) alterations in Alzheimer's disease (AD), even in individuals with mild cognitive impairment (MCI). Further, impaired sleep and circadian patterns are common symptoms of AD, while sleep and circadian rhythm disruption (SCRD) is associated with greater β-amyloid (Aβ) burden and AD risk, sometimes years before the clinical onset of AD. Moreover, reports have demonstrated that GM and its metabolites exhibit diurnal rhythmicity and the role of SCRD in dampening the GM rhythmicity and eubiosis. This review will provide an evaluation of clinical and animal studies describing GM alterations in distinct conditions, including AD, sleep and circadian disruption. It aims to identify the overlapping and distinctive GM alterations in these conditions and their contributions to pathophysiology. Although most studies are observational and use different methodologies, data indicate partial commonalities in GM alterations and unanimity at functional level. Finally, we discuss the possible interactions between SCRD and GM in AD pathogenesis, as well as several methodological improvements that are necessary for future research.
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Affiliation(s)
- Yi Li
- School of Medicine, Imperial College London, London, UK
| | - Lingzhan Shao
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
| | - Yang Mou
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
| | - Yan Zhang
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
| | - Yong Ping
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China,Shanghai Mental Health Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China,CONTACT Yong Ping Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
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Zhou Y, Lu W, Yang G, Chen Y, Cao J, Zhou C. Bile acid metabolism and liver fibrosis following treatment with bifid triple viable capsules in nonalcoholic fatty liver disease. Am J Transl Res 2021; 13:13485-13497. [PMID: 35035690 PMCID: PMC8748085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 10/14/2021] [Indexed: 06/14/2023]
Abstract
PURPOSE This study investigated liver enzymes, bile acid metabolism, and liver fibrosis in nonalcoholic fatty liver disease (NAFLD) to evaluate the therapeutic effects of microecological preparations on fatty liver. METHODS Liver enzymes, liver fibrosis, and bile acids were assessed in 40 healthy volunteers and 124 NAFLD patients. All patients were retested for liver enzymes, bile acids, and liver fibrosis after two months of bifid triple viable capsule therapy. Results: (1) Prior to treatment, alanine aminotransferase, aspartate aminotransferase, glutamyl transpeptidase, FibroScan liver stiffness, total bile acid, chenodeoxycholic acid, deoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, glycodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, and taurolithocholic acid increased with the severity of NAFLD (P<0.05). Primary/secondary bile acids increased in patients compared to healthy controls; free/conjugated bile acids decreased (P<0.05). (2) We detected a positive correlation between total bile acid, cholic acid, chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, glycodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, taurolithocholic acid, tauroursodeoxycholic acid, and FibroScan liver stiffness. (3) Following treatment, liver enzymes decreased. Bile acids were impacted by decreasing primary/secondary bile acids and increasing free/conjugated bile acids. Improvements were observed in the fibrosis of mild fatty liver. No effects were observed for moderate and severe fatty liver. CONCLUSIONS Liver enzymes, bile acids, and liver fibrosis were correlated with the severity of NAFLD. There were positive correlations between bile acids and liver fibrosis. Bifid triple viable capsules could decrease liver enzymes and impact bile acid metabolism but failed to effectively improve liver fibrosis.
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Affiliation(s)
- Yuqing Zhou
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University Suzhou, Jiangsu, China
| | - Wen Lu
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University Suzhou, Jiangsu, China
| | - Guorong Yang
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University Suzhou, Jiangsu, China
| | - Yifeng Chen
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University Suzhou, Jiangsu, China
| | - Jiwei Cao
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University Suzhou, Jiangsu, China
| | - Chunli Zhou
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University Suzhou, Jiangsu, China
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Zhang Y, Yang L, Zhao N, Hong Z, Cai B, Le Q, Yang T, Shi L, He J. Soluble Polysaccharide Derived from Laminaria japonica Attenuates Obesity-Related Nonalcoholic Fatty Liver Disease Associated with Gut Microbiota Regulation. Mar Drugs 2021; 19:699. [PMID: 34940698 PMCID: PMC8706399 DOI: 10.3390/md19120699] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 12/07/2021] [Accepted: 12/08/2021] [Indexed: 01/22/2023] Open
Abstract
In this study, the effects of a polysaccharide derived from Laminaria japonica (LJP) on obesity were investigated in mice fed a high-fat diet (HFD). LJP significantly attenuated obesity-related features, lowering serum triglycerides, glucose, total cholesterol and low-density lipoprotein cholesterol levels. HFD-induced liver steatosis and hepatocellular ballooning were significantly attenuated by LJP. Additionally, LJP was found to significantly modulate hepatic gene expressions of AMPK and HMGCR, which are key regulators of lipid and cholesterol metabolism. We further found that LJP ameliorated HFD-induced gut microbiota (GM) dysbiosis by significantly reducing the obesity-related Firmicutes to Bacteroidetes ratio, meanwhile promoting the growth of Verrucomicrobia at the phylum level. At the genus level, propionate-producing bacteria Bacteroides and Akkermansia were elevated by LJP, which might explain the result that LJP elevated fecal propionate concentration. Taken together, these findings suggest that dietary intake of LJP modulates hepatic energy homeostasis to alleviate obesity-related nonalcoholic fatty liver disease associated with GM regulation.
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Affiliation(s)
- Yiping Zhang
- Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China; (Y.Z.); (L.Y.); (N.Z.); (Z.H.); (B.C.); (Q.L.); (T.Y.); (L.S.)
- Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China
| | - Longhe Yang
- Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China; (Y.Z.); (L.Y.); (N.Z.); (Z.H.); (B.C.); (Q.L.); (T.Y.); (L.S.)
- Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China
| | - Nannan Zhao
- Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China; (Y.Z.); (L.Y.); (N.Z.); (Z.H.); (B.C.); (Q.L.); (T.Y.); (L.S.)
- Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China
| | - Zhuan Hong
- Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China; (Y.Z.); (L.Y.); (N.Z.); (Z.H.); (B.C.); (Q.L.); (T.Y.); (L.S.)
- Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China
| | - Bing Cai
- Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China; (Y.Z.); (L.Y.); (N.Z.); (Z.H.); (B.C.); (Q.L.); (T.Y.); (L.S.)
- Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China
| | - Qingqing Le
- Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China; (Y.Z.); (L.Y.); (N.Z.); (Z.H.); (B.C.); (Q.L.); (T.Y.); (L.S.)
- Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China
| | - Ting Yang
- Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China; (Y.Z.); (L.Y.); (N.Z.); (Z.H.); (B.C.); (Q.L.); (T.Y.); (L.S.)
- Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China
| | - Lijun Shi
- Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China; (Y.Z.); (L.Y.); (N.Z.); (Z.H.); (B.C.); (Q.L.); (T.Y.); (L.S.)
- Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China
| | - Jianlin He
- Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China; (Y.Z.); (L.Y.); (N.Z.); (Z.H.); (B.C.); (Q.L.); (T.Y.); (L.S.)
- Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China
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Lonardo A. Separating the apples from the oranges: from NAFLD heterogeneity to personalized medicine. EXPLORATION OF MEDICINE 2021. [DOI: 10.37349/emed.2021.00061] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 10/09/2021] [Indexed: 01/11/2025] Open
Abstract
Recently, Arrese and Colleagues have published a review article entitled, “Insights into Nonalcoholic Fatty-Liver Disease (NAFLD) Heterogeneity” (Semin Liver Dis. 2021;41:421-34. doi: 10.1055/s-0041-1730927). This milestone publication clearly and exhaustively explains the multitude of pathogenic pathways involved in the development and progression of disease eventually conducive to heterogeneous clinical phenotypes and different disease outcomes. The present commentary first briefly discusses the biological grounds of NAFLD heterogeneity and then illustrates the work by Arrese et al. In conclusion, the presently adopted nomenclatures appear inadequate in rendering the complexity of disease in the individual patient. In order to adopt the principles of personalized care, what remains to be done is to propose and validate a simple and accurate classification system. This should give full consideration to the principal disease modifiers and should shape a scheme to be adopted in both clinical practice and in the research arena. Care should be taken to not neglect the systemic nature of disease.
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Affiliation(s)
- Amedeo Lonardo
- Department of Internal Medicine, Azienda Ospedaliero-Universitaria of Modena, 41100 Modena, Italy
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Liu X, Zhao K, Jing N, Kong Q, Yang X. Epigallocatechin Gallate (EGCG) Promotes the Immune Function of Ileum in High Fat Diet Fed Mice by Regulating Gut Microbiome Profiling and Immunoglobulin Production. Front Nutr 2021; 8:720439. [PMID: 34616764 PMCID: PMC8488439 DOI: 10.3389/fnut.2021.720439] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 07/19/2021] [Indexed: 01/24/2023] Open
Abstract
This study aimed to investigate the regulatory effect of epigallocatechin gallate (EGCG) on the composition of the gut microbiome, the transcriptomic profiling of ileum, and their interplay in high fat diet (HFD) induced obese mice. Intragastric administration of EGCG to C57BL/6J mice for 14 consecutive weeks remarkably decreased HFD induced excessive fat deposition (p < 0.001), and the increment of serum TG, TC, HDL-C (p < 0.05), as well as improved glucose tolerance (p < 0.001). EGCG shifted the gut microbiota mainly by elevating the relative abundance of Parasutterrlla, Bacteroides, and Akkermansia (p < 0.01), decreasing that of norank_f_Erysipelotrichaceae, unclassified_f_Ruminococcaceae, Anaerotruncus, Roseburia, norank_Lachnospiraceae, and Lachnospiraceae_UCG_006 (p < 0.01) at the genus level. In addition, EGCG affected the transcriptomic profiling of ileum, and the differentially expressed (DE) genes after HFD or/and EGCG treatment were mostly enriched in the immune reaction of ileum, such as the GO term of “immune effector process” and “phagocytosis, recognition.” Furthermore, the KEGG category of “immune diseases,” “immune system,” and “infection diseases: bacterial” were commonly enriched by the DE genes of the two treatments. Among those DE genes, 16 immunoglobulins heavy chain variable region encoded genes (Ighvs) and other immunity-related genes, such as complement component 2 (C2), interferon-induced transmembrane protein 1 (Iftm1), polymeric immunoglobulin receptor (pigR), and alanyl aminopeptidase (Anpep), were highly correlated with the shifted microbes in the gut (p < 0.05, absolute r > 0.5). Overall, the results suggested that EGCG ameliorated the HFD induced metabolic disorder mainly by regulating gut microbiome profiling and the immunoglobulin production of ileum, while the genes expressed in the ileum, especially Ighvs, C2, Iftm1, pigR, and Anpep, might play important roles in coordinating the immunity of mice regarding the gut microbes and the host interactions.
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Affiliation(s)
- Xiaoxia Liu
- Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou, China.,Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, and Xi'an Key Laboratory of Characteristic Fruit Storage and Fresh-keeping, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, China
| | - Ke Zhao
- Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou, China.,Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, and Xi'an Key Laboratory of Characteristic Fruit Storage and Fresh-keeping, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, China
| | - Nana Jing
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, and Xi'an Key Laboratory of Characteristic Fruit Storage and Fresh-keeping, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, China
| | - Qingjun Kong
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, and Xi'an Key Laboratory of Characteristic Fruit Storage and Fresh-keeping, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, China
| | - Xingbin Yang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, and Xi'an Key Laboratory of Characteristic Fruit Storage and Fresh-keeping, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, China
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30
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Kumar V, Xin X, Ma J, Tan C, Osna N, Mahato RI. Therapeutic targets, novel drugs, and delivery systems for diabetes associated NAFLD and liver fibrosis. Adv Drug Deliv Rev 2021; 176:113888. [PMID: 34314787 PMCID: PMC8440458 DOI: 10.1016/j.addr.2021.113888] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 06/12/2021] [Accepted: 07/18/2021] [Indexed: 02/08/2023]
Abstract
Type 2 diabetes mellitus (T2DM) associated non-alcoholic fatty liver disease (NAFLD) is the fourth-leading cause of death. Hyperglycemia induces various complications, including nephropathy, cirrhosis and eventually hepatocellular carcinoma (HCC). There are several etiological factors leading to liver disease development, which involve insulin resistance and oxidative stress. Free fatty acid (FFA) accumulation in the liver exerts oxidative and endoplasmic reticulum (ER) stresses. Hepatocyte injury induces release of inflammatory cytokines from Kupffer cells (KCs), which are responsible for activating hepatic stellate cells (HSCs). In this review, we will discuss various molecular targets for treating chronic liver diseases, including homeostasis of FFA, lipid metabolism, and decrease in hepatocyte apoptosis, role of growth factors, and regulation of epithelial-to-mesenchymal transition (EMT) and HSC activation. This review will also critically assess different strategies to enhance drug delivery to different cell types. Targeting nanocarriers to specific liver cell types have the potential to increase efficacy and suppress off-target effects.
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Affiliation(s)
- Virender Kumar
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Xiaofei Xin
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Jingyi Ma
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Chalet Tan
- Department of Pharmaceutics and Drug Delivery, University of Mississippi, University, MS 38677, USA
| | - Natalia Osna
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA
| | - Ram I Mahato
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA.
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31
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Ming J, Yu X, Xu X, Wang L, Ding C, Wang Z, Xie X, Li S, Yang W, Luo S, He Q, Du Y, Tian Z, Gao X, Ma K, Fang Y, Li C, Zhao J, Wang X, Ji Q. Effectiveness and safety of Bifidobacterium and berberine in human hyperglycemia and their regulatory effect on the gut microbiota: a multi-center, double-blind, randomized, parallel-controlled study. Genome Med 2021; 13:125. [PMID: 34365978 PMCID: PMC8351344 DOI: 10.1186/s13073-021-00942-7] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 07/21/2021] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Berberine and Bifidobacterium have been reported to improve glucose tolerance in people with hyperglycemia or other metabolic disorders. This study aimed to assess the hypoglycemic effect and the regulation of the gut microbiota caused by berberine and Bifidobacterium and the possible additive benefits of their combination. METHODS This was an 18-week, multi-center, randomized, double-blind, parallel-controlled study of patients newly diagnosed with hyperglycemia. After a 2-week run-in period, 300 participants were randomly assigned to the following four groups for 16 weeks of treatment: berberine (Be), Bifidobacterium (Bi), berberine and Bifidobacterium (BB), and placebo group. The primary efficacy endpoint was the absolute value of fasting plasma glucose (FPG) compared with baseline after 16 weeks of treatment. RESULTS Between October 2015 and April 2018, a total of 297 participants were included in the primary analysis. Significant reductions of FPG were observed in the Be and BB groups compared with the placebo group, with a least square (LS) mean difference of - 0.50, 95% CI [- 0.85, - 0.15] mmol/L, and - 0.55, 95% CI [- 0.91, - 0.20] mmol/L, respectively. The Be and BB groups also showed significant reductions in 2-h postprandial plasma glucose. A pronounced decrease in HbA1c occurred in the BB group compared to the placebo group. Moreover, compared with the Bi and placebo groups, the Be and BB groups had more changes in the gut microbiota from the baseline. CONCLUSIONS Berberine could regulate the structure and function of the human gut microbiota, and Bifidobacterium has the potential to enhance the hypoglycemic effect of berberine. These findings provide new insights into the hypoglycemic potential of berberine and Bifidobacterium. TRIAL REGISTRATION ClinicalTrials.gov , NCT03330184. Retrospectively registered on 18 October 2017.
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Affiliation(s)
- Jie Ming
- Endocrinology Research Center, Department of Endocrinology and Metabolism, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
| | - Xinwen Yu
- Endocrinology Research Center, Department of Endocrinology and Metabolism, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
| | | | - Li Wang
- Endocrinology Research Center, Department of Endocrinology and Metabolism, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
| | - Chao Ding
- Department of General Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | | | - Xuan Xie
- Department of Endocrinology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Sheli Li
- Department of Endocrinology, Affiliated Hospital of Yan'an University, Yan'an, China
| | - Wenjuan Yang
- The Fifth Department of Internal Medicine, Shaanxi Aerospace Hospital, Xi'an, China
- Department of Endocrinology, Xi'an Daxing Hospital, Xi'an, China
| | - Shu Luo
- Genertec Universal Xi'an Aero-Engine Hospital, Xi'an, China
| | - Qingzhen He
- Department of Endocrinology, Xi'an High-Tech Hospital, Xi'an, China
| | - Yafang Du
- Department of Endocrinology, Chang'an Hospital, Xi'an, China
| | - Zhufang Tian
- Department of Endocrinology, Xi'an Central Hospital, Xi'an, China
| | - Xiling Gao
- Department of Endocrinology, Yan'an People's Hospital, Yan'an, China
| | - Kaiyan Ma
- Department of Endocrinology, Shangluo Central Hospital, Shangluo, China
| | - Yujie Fang
- Endocrinology Research Center, Department of Endocrinology and Metabolism, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
| | - Chen Li
- Department of Health Statistics, Fourth Military Medical University, Xi'an, China
| | - Jiajun Zhao
- Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
| | | | - Qiuhe Ji
- Endocrinology Research Center, Department of Endocrinology and Metabolism, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
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32
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Gao LL, Ma JM, Fan YN, Zhang YN, Ge R, Tao XJ, Zhang MW, Gao QH, Yang JJ. Lycium barbarum polysaccharide combined with aerobic exercise ameliorated nonalcoholic fatty liver disease through restoring gut microbiota, intestinal barrier and inhibiting hepatic inflammation. Int J Biol Macromol 2021; 183:1379-1392. [PMID: 33992651 DOI: 10.1016/j.ijbiomac.2021.05.066] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 05/04/2021] [Accepted: 05/10/2021] [Indexed: 12/28/2022]
Abstract
Gut microbiota and intestinal permeability have been demonstrated to be the key players in the gut-liver cross talk in nonalcoholic fatty liver disease (NAFLD). Lycium barbarum polysaccharides (LBPs), which seem to be a potential prebiotic, and aerobic exercise (AE) have shown protective effects on NAFLD. However, their combined effects on intestinal microecology remain unclear. This study evaluated the effects of LBP, AE, and its combination (LBP + AE) on gut microbiota composition, intestinal barrier, and hepatic inflammation in NAFLD. LBP + AE showed high abundance and diversity of gut microbiota, restored the gut microbiota composition, increased some Bacteroidetes, short chain fatty acids, but decreased Proteobacteria and the ratio of Firmicutes/Bacteroidetes. Simultaneously, LBP, AE, and LBP + AE could restore the colonic and ileum tight junctions by increasing the expression of zonula occludens-1 and occludin. They also downregulated gut-derived lipopolysaccharides (LPSs), hepatic LPS-binding proteins, inflammatory factors, and related indicators of the LPS/TLR4/NF-κB signaling pathway for the liver. Our results implied that LBP could be considered a prebiotic agent, and LBP + AE might be a promising treatment for NAFLD because it could maintain gut microbiota balance, thereby restoring intestinal barrier and exerting hepatic benefits.
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Affiliation(s)
- Lu-Lu Gao
- School of Public Health and Management, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750004, China.
| | - Jia-Min Ma
- School of Public Health and Management, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750004, China
| | - Yan-Na Fan
- School of Public Health and Management, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750004, China
| | - Yan-Nan Zhang
- School of Public Health and Management, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750004, China
| | - Rui Ge
- School of Public Health and Management, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750004, China
| | - Xiu-Juan Tao
- School of Public Health and Management, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750004, China
| | - Meng-Wei Zhang
- School of Public Health and Management, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750004, China
| | - Qing-Han Gao
- School of Public Health and Management, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750004, China.
| | - Jian-Jun Yang
- School of Public Health and Management, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750004, China.
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33
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Su Q, Liu Q. Factors Affecting Gut Microbiome in Daily Diet. Front Nutr 2021; 8:644138. [PMID: 34041257 PMCID: PMC8141808 DOI: 10.3389/fnut.2021.644138] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Accepted: 04/16/2021] [Indexed: 12/13/2022] Open
Abstract
There is a growing recognition that a good diet can help people maintain mental and physical health, while a bad one will cause the disorder of body function, and even lead to several diseases. A lot of attentions have been devoted to analyze every possible health-related factor in the daily diet, including food ingredients, additives, and cooking process. With the support of high-throughput sequencing technology, there is accumulating evidence gradually clarifying that most of these factors are mainly through the interactions with gut microbiome to trigger downstream effects. The gut microbiome may be able to act as a very sensitive mirror in response to human daily diet. A complex network of interactions among diet, gut microbiome, and health has been gradually depicted, but it is rarely discussed from a more comprehensive perspective. To this end, this review summarized the latest updates in diet-gut microbiome interactions, analyzed most identified factors involved in this process, showed the possibility of maintaining health or alleviating diseases by diet intervention, aiming to help people choose a suitable recipe more accurately.
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Affiliation(s)
| | - Qin Liu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
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34
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Lonardo A, Arab JP, Arrese M. Perspectives on Precision Medicine Approaches to NAFLD Diagnosis and Management. Adv Ther 2021; 38:2130-2158. [PMID: 33829368 PMCID: PMC8107169 DOI: 10.1007/s12325-021-01690-1] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 02/26/2021] [Indexed: 02/06/2023]
Abstract
Precision medicine defines the attempt to identify the most effective approaches for specific subsets of patients based on their genetic background, clinical features, and environmental factors. Nonalcoholic fatty liver disease (NAFLD) encompasses the alcohol-like spectrum of liver disorders (steatosis, steatohepatitis with/without fibrosis, and cirrhosis and hepatocellular carcinoma) in the nonalcoholic patient. Recently, disease renaming to MAFLD [metabolic (dysfunction)-associated fatty liver disease] and positive criteria for diagnosis have been proposed. This review article is specifically devoted to envisaging some clues that may be useful to implementing a precision medicine-oriented approach in research and clinical practice. To this end, we focus on how sex and reproductive status, genetics, intestinal microbiota diversity, endocrine and metabolic status, as well as physical activity may interact in determining NAFLD/MAFLD heterogeneity. All these factors should be considered in the individual patient with the aim of implementing an individualized therapeutic plan. The impact of considering NAFLD heterogeneity on the development of targeted therapies for NAFLD subgroups is also extensively discussed.
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Affiliation(s)
- Amedeo Lonardo
- Department of Internal Medicine, Azienda Ospedaliero-Universitaria, Ospedale Civile di Baggiovara, 1135 Via Giardini, 41126, Modena, Italy.
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Departamento de Biología Celular y Molecular, Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Marco Arrese
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Departamento de Biología Celular y Molecular, Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
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35
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Abenavoli L, Procopio AC, Scarpellini E, Polimeni N, Aquila I, Larussa T, Boccuto L, Luzza F. Gut microbiota and non-alcoholic fatty liver disease: a narrative review. Minerva Gastroenterol (Torino) 2021; 67:339-347. [PMID: 33871224 DOI: 10.23736/s2724-5985.21.02896-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The gastrointestinal tract of the adult human represents the habitat of the ecological community of commensal, symbiotic and pathogenic microorganisms, defined as the gut microbiota, which has more than 100 trillion microorganisms representing one of the most complex ecosystems. Colonization of the gastrointestinal tract by microorganisms begins at the time of birth. Contrary to what was previously hypothesized, a large number of fundamental functions for the host are attributed to the gut microbiota to date. The gut microbiota, therefore, does not represent a passive set of microbes hosted inside the human organism but plays a crucial role in the balance of the organism itself. An alteration of the microbiota is a phenomenon known as dysbiosis. The latter can be implicated in the development of complex liver diseases like non-alcoholic fatty liver disease. The aim of this review is to describe the most interesting data linking the development of non-alcoholic fatty liver disease with the gut microbiota and, therefore, to underline the importance of the microbiota itself, as a potential therapeutic target in the treatment of non-alcoholic fatty liver disease.
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Affiliation(s)
- Ludovico Abenavoli
- Department of Health Sciences, Magna Graecia University, Catanzaro, Italy -
| | - Anna C Procopio
- Department of Health Sciences, Magna Graecia University, Catanzaro, Italy
| | - Emidio Scarpellini
- Clinical Nutrition Unit and Internal Medicine Unit, Madonna del Soccorso General Hospital, San Benedetto del Tronto, Ascoli Piceno, Italy
| | - Natale Polimeni
- Digestive Disease Endoscopy Unit, Madonna della Consolazione Hospital, Reggio Calabria, Italy
| | - Isabella Aquila
- Department of Health Sciences, Magna Graecia University, Catanzaro, Italy
| | - Tiziana Larussa
- Department of Health Sciences, Magna Graecia University, Catanzaro, Italy
| | - Luigi Boccuto
- School of Nursing, College of Behavioral, Social and Health Sciences, Clemson University, Clemson, SC, USA
| | - Francesco Luzza
- Department of Health Sciences, Magna Graecia University, Catanzaro, Italy
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36
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Ni J, Fu C, Huang R, Li Z, Li S, Cao P, Zhong K, Ge M, Gao Y. Metabolic syndrome cannot mask the changes of faecal microbiota compositions caused by primary hepatocellular carcinoma. Lett Appl Microbiol 2021; 73:73-80. [PMID: 33768575 DOI: 10.1111/lam.13477] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 03/16/2021] [Accepted: 03/22/2021] [Indexed: 12/19/2022]
Abstract
Both hepatocellular carcinoma (HCC) and metabolic syndrome are closely associated with the composition of the gut microbiota (GM). Although it has been proposed that elements of the GM can be used as biomarkers for the early diagnosis of HCC, whether metabolic syndrome results in a misrepresentation of the results of the early diagnosis of HCC using GM remains unclear. We compared the differences in the faecal microbiota of 10 patients with primary HCC, six patients with type 2 diabetes mellitus (T2DM), seven patients with arterial hypertension, six patients with both HCC and T2DM, and 10 patients with both HCC and arterial hypertension, as well as 10 healthy subjects, using high-throughput sequencing of 16S rRNA gene amplicons. Our results revealed a significant difference in the GM between subjects with and without HCC. The 49 bacterial genera out of the 494 detected genera were significantly different between the groups. These results show that changes in the GM can be used to distinguish between subjects with and without HCC, and can resist interference of T2DM and arterial hypertension with the GM. The results of the present study provide an important basis for the clinical auxiliary diagnosis of HCC by detecting the GM.
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Affiliation(s)
- J Ni
- Research and Development Center, Guangdong Meilikang Bio-Sciences Ltd., Dongguan, China.,Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center of Artificial Organ and Tissue Engineering, Zhujiang Hospital of Southern Medical University, Guangzhou, China.,Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research, Guangdong Medical University, Dongguan, China
| | - C Fu
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center of Artificial Organ and Tissue Engineering, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - R Huang
- Department of Neonatal Surgery, Guangdong Women and Children Hospital, Guangzhou, China
| | - Z Li
- Research and Development Center, Guangdong Meilikang Bio-Sciences Ltd., Dongguan, China
| | - S Li
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center of Artificial Organ and Tissue Engineering, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - P Cao
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center of Artificial Organ and Tissue Engineering, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - K Zhong
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center of Artificial Organ and Tissue Engineering, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - M Ge
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center of Artificial Organ and Tissue Engineering, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - Y Gao
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center of Artificial Organ and Tissue Engineering, Zhujiang Hospital of Southern Medical University, Guangzhou, China.,State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China
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37
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Sindi AS, Geddes DT, Wlodek ME, Muhlhausler BS, Payne MS, Stinson LF. Can we modulate the breastfed infant gut microbiota through maternal diet? FEMS Microbiol Rev 2021; 45:6133472. [PMID: 33571360 DOI: 10.1093/femsre/fuab011] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 02/09/2021] [Indexed: 12/11/2022] Open
Abstract
Initial colonisation of the infant gut is robustly influenced by regular ingestion of human milk, a substance that contains microbes, microbial metabolites, immune proteins, and oligosaccharides. Numerous factors have been identified as potential determinants of the human milk and infant gut microbiota, including maternal diet; however, there is limited data on the influence of maternal diet during lactation on either of these. Here, we review the processes thought to contribute to human milk and infant gut bacterial colonisation and provide a basis for considering the role of maternal dietary patterns during lactation in shaping infant gut microbial composition and function. Although only one observational study has directly investigated the influence of maternal diet during lactation on the infant gut microbiome, data from animal studies suggests that modulation of the maternal gut microbiota, via diet or probiotics, may influence the mammary or milk microbiota. Additionally, evidence from human studies suggests that the maternal diet during pregnancy may affect the gut microbiota of the breastfed infant. Together, there is a plausible hypothesis that maternal diet during lactation may influence the infant gut microbiota. If substantiated in further studies, this may present a potential window of opportunity for modulating the infant gut microbiome in early life.
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Affiliation(s)
- Azhar S Sindi
- Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia.,College of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Donna T Geddes
- School of Molecular Sciences, The University of Western Australia, Perth, Western Australia, Australia
| | - Mary E Wlodek
- Department of Physiology, University of Melbourne, Melbourne, Victoria, Australia
| | - Beverly S Muhlhausler
- CSIRO, Adelaide, South Australia, Australia.,School of Agriculture, Food and Wine, The University of Adelaide, Adelaide, South Australia, Australia
| | - Matthew S Payne
- Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia
| | - Lisa F Stinson
- School of Molecular Sciences, The University of Western Australia, Perth, Western Australia, Australia
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38
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Luo Y, Lin H. Inflammation initiates a vicious cycle between obesity and nonalcoholic fatty liver disease. IMMUNITY INFLAMMATION AND DISEASE 2020; 9:59-73. [PMID: 33332766 PMCID: PMC7860600 DOI: 10.1002/iid3.391] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 11/23/2020] [Accepted: 11/26/2020] [Indexed: 12/14/2022]
Abstract
Low‐level of chronic inflammation activation is characteristic of obesity. Nonalcoholic fatty liver disease (NAFLD) is closely linked to obesity and is an emerging health problem, it originates from abnormal accumulation of triglycerides in the liver, and sometimes causes inflammatory reactions that could contribute to cirrhosis and liver cancer, thus its pathogenesis needs to be clarified for more treatment options. Once NAFLD is established, it contributes to systemic inflammation, the low‐grade inflammation is continuously maintained during NAFLD causing impaired resolution of inflammation in obesity, which subsequently exacerbates its severity. This study focuses on the effects of obesity‐induced inflammations, which are the underlying causes of the disease progression and development of more severe inflammatory and fibrotic stages. Understanding the relationship between obesity and NAFLD could help in establishing attractive therapeutic targets or diagnostic markers in obesity‐induced inflammation response and provides new approaches for the prevention and treatment of NAFLD in obesity.
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Affiliation(s)
- Yunfei Luo
- Department of Pathophysiology, Schools of Basic Sciences, Jiangxi Provincial Key Laboratory of Tumor Pathogens and Molecular Pathology, Nanchang University, Nanchang, China
| | - Hui Lin
- Department of Pathophysiology, Schools of Basic Sciences, Jiangxi Provincial Key Laboratory of Tumor Pathogens and Molecular Pathology, Nanchang University, Nanchang, China
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39
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Zubeldia-Varela E, Barber D, Barbas C, Perez-Gordo M, Rojo D. Sample pre-treatment procedures for the omics analysis of human gut microbiota: Turning points, tips and tricks for gene sequencing and metabolomics. J Pharm Biomed Anal 2020; 191:113592. [PMID: 32947167 DOI: 10.1016/j.jpba.2020.113592] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 07/29/2020] [Accepted: 08/23/2020] [Indexed: 02/06/2023]
Abstract
The connection between gut microbiota and human health is becoming increasingly relevant and the number of groups working in this field is constantly growing. In this context, from high-throughput gene sequencing to metabolomics analysis, the omics technologies have contributed enormously to unveil the secret crosstalk between us and our microbes. All the omics technologies produce a great amount of information, and processing this information is time-consuming and expensive. For this reason, a correct experimental design and a careful pre-analytical planning are crucial. To study the human gut microbiota, faeces are the sample of choice. Faecal material is complex, and procedures for collecting and preserving faeces are not well-established. Furthermore, increasing evidence suggests that multiple confounding factors, such as antibiotics consumption, mode of delivery, diet, aging and several diseases and disorders can alter the composition and functionality of the microbiota. This review is focused on the discussion of critical general issues during the pre-analytical planning, from patient handling to faeces sampling, including collection procedures, transport, storage conditions and possible pre-treatments, which are critical for a successful research in omics with a special attention to metabolomics and gene sequencing. We also point out that the adoption of standard operating procedures in the field is needed to guarantee accuracy and reproducibility of results.
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Affiliation(s)
- Elisa Zubeldia-Varela
- Centre for Metabolomics and Bioanalysis (CEMBIO), Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain; Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Universidad San Pablo-CEU, CEU Universities, ARADyAL, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain
| | - Domingo Barber
- Institute of Applied and Molecular Medicine (IMMA), Facultad de Medicina, Universidad San Pablo-CEU, CEU Universities, ARADyAL, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain
| | - Coral Barbas
- Centre for Metabolomics and Bioanalysis (CEMBIO), Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain
| | - Marina Perez-Gordo
- Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Universidad San Pablo-CEU, CEU Universities, ARADyAL, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain; Institute of Applied and Molecular Medicine (IMMA), Facultad de Medicina, Universidad San Pablo-CEU, CEU Universities, ARADyAL, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain
| | - David Rojo
- Centre for Metabolomics and Bioanalysis (CEMBIO), Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain.
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Zhang M, Wang Z, Hao S, Hao L, Zhang X, Yu P, Sun H. Synthesis of natural 3'-Prenylchalconaringenin and biological evaluation of ameliorating non-alcoholic fatty liver disease and metabolic syndrome. Eur J Med Chem 2020; 205:112649. [PMID: 32791402 DOI: 10.1016/j.ejmech.2020.112649] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 07/07/2020] [Accepted: 07/07/2020] [Indexed: 12/22/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and important risk factor for cardiac diseases, diabetes and extrahepatic cancers. Natural 3'-geranylchalconaringenin (GC) and desmethylxanthohumol (DX) from hop were synthesized using a regio-selective iodination and the Suzuki coupling reaction as key steps. GC and DX, along with their aglycone naringenin chalcone (NC) were investigated their decreasing the accumulation of cellular lipids. GC reduced lipid content and activated the AMP-activated protein kinase (AMPK) pathway in HepG2 and 3T3-L1 cells. In addition, GC had an obvious therapeutic effect on alleviating NAFLD and metabolic syndrome by activating the AMPK pathway in vivo. In conclusion, GC may be potentially used as a candidate drug and functional food for treating NAFLD and metabolic syndrome.
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Affiliation(s)
- Mengdi Zhang
- China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, PR China
| | - Zhaoxin Wang
- China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, PR China
| | - Siyu Hao
- China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, PR China
| | - Lei Hao
- China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, PR China
| | - Xinying Zhang
- China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, PR China
| | - Peng Yu
- China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, PR China.
| | - Hua Sun
- China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, PR China.
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Shao M, Ye Z, Qin Y, Wu T. Abnormal metabolic processes involved in the pathogenesis of non-alcoholic fatty liver disease (Review). Exp Ther Med 2020; 20:26. [PMID: 32934691 PMCID: PMC7471863 DOI: 10.3892/etm.2020.9154] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 05/28/2020] [Indexed: 12/13/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and can lead to liver cirrhosis or liver cancer in severe cases. In recent years, the incidence of NAFLD has increased substantially. The trend has continued to increase and has become a key point of concern for health systems. NAFLD is often associated with metabolic abnormalities caused by increased visceral obesity, including insulin resistance, diabetes mellitus, hypertension, dyslipidemia, atherosclerosis and systemic microinflammation. Therefore, the pathophysiological mechanisms of NAFLD must be clarified to develop new drug treatment strategies. Recently, researchers have conducted numerous studies on the pathogenesis of NAFLD and have identified various important regulatory factors and potential molecular mechanisms, providing new targets and a theoretical basis for the treatment of NAFLD. However, the pathogenesis of NAFLD is extremely complex and involves the interrelationship and influence of multiple organs and systems. Therefore, the condition must be explored further. In the present review, the abnormal metabolic process, including glucose, lipid, amino acid, bile acid and iron metabolism are reviewed. It was concluded that NAFLD is associated with an imbalanced metabolic network that involves glucose, lipids, amino acids, bile acids and iron, and lipid metabolism is the core metabolic process. The current study aimed to provide evidence and hypotheses for research and clinical treatment of NAFLD.
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Affiliation(s)
- Mingmei Shao
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
| | - Zixiang Ye
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
| | - Yanhong Qin
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
| | - Tao Wu
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
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Longo L, Tonin Ferrari J, Rampelotto PH, Hirata Dellavia G, Pasqualotto A, P Oliveira C, Thadeu Schmidt Cerski C, Reverbel da Silveira T, Uribe-Cruz C, Álvares-da-Silva MR. Gut Dysbiosis and Increased Intestinal Permeability Drive microRNAs, NLRP-3 Inflammasome and Liver Fibrosis in a Nutritional Model of Non-Alcoholic Steatohepatitis in Adult Male Sprague Dawley Rats. Clin Exp Gastroenterol 2020; 13:351-368. [PMID: 32982365 PMCID: PMC7509481 DOI: 10.2147/ceg.s262879] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Accepted: 07/23/2020] [Indexed: 12/12/2022] Open
Abstract
Background/Aim The interactions between the gut and liver have been described in the progression of non-alcoholic steatohepatitis (NASH). The aim of this study was to develop an experimental nutritional model of NASH simulating metabolic changes occurring in humans. Materials and Methods Adult male Sprague Dawley rats were randomized into two groups: controls (standard diet) and intervention (high-fat and choline-deficient diet) for 16 weeks, each experimental group with 10 animals. Biochemical analysis, hepatic lipid content, microRNAs, inflammatory, gut permeability markers and gut microbiota were measured. Results Animals in the intervention group showed significantly higher delta Lee index (p=0.017), abdominal circumference (p<0.001), abdominal adipose tissue (p<0.001) and fresh liver weight (p<0.001), as well as higher serum levels of alanine aminotransferase (p=0.010), glucose (p=0.013), total cholesterol (p=0.033), LDL cholesterol (p=0.011), and triglycerides (p=0.011), and lower HDL cholesterol (p=0.006) compared to the control group. Higher TLR4 (p=0.041), TLR9 (p=0.033), MyD88 (p=0.001), Casp1 (p<0.001), NLPR3 (p=0.019), liver inflammation index interleukin (IL)-1β/IL10 (p<0.001), IL6/IL10 (p=0.002) and TNFα/IL10 (p=0.001) were observed in the intervention group, and also lower permeability markers Ocln (p=0.003) and F11r (p=0.041). Gene expression of miR-122 increased (p=0.041) and miR-145 (p=0.010) decreased in the intervention group. Liver steatosis, inflammation and fibrosis, along with collagen fiber deposition increment (p<0.001), were seen in the intervention group. Regarding gut microbiota, Bray-Curtis dissimilarity index and number of operational taxonomic units were significantly different (p<0.001) between the groups. Composition of the gut microbiota showed a significant correlation with histopathological score of NAFLD (r=0.694) and index IL-1β/IL-10 (r=0.522). Conclusion This experimental model mimicking human NASH demonstrated gut and liver interaction, with gut microbiota and intestinal permeability changes occurring in parallel with systemic and liver inflammation, miRNAs regulation and liver tissue damage.
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Affiliation(s)
- Larisse Longo
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.,Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Jéssica Tonin Ferrari
- Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Pabulo Henrique Rampelotto
- Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.,Graduate Program in Pharmaceutical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Gustavo Hirata Dellavia
- School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Amanda Pasqualotto
- Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Claudia P Oliveira
- Department of Gastroenterology (LIM07), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Carlos Thadeu Schmidt Cerski
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.,School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.,Unit of Surgical Pathology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Themis Reverbel da Silveira
- Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Carolina Uribe-Cruz
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.,Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Mário Reis Álvares-da-Silva
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.,Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.,School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.,Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
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Wang CZ, Wan JY, Wan J, Wang S, Luo Y, Zeng J, Yao H, Zhang CF, Zhang QH, Sawadogo WR, Xu M, Du W, Qi LW, Li P, Yuan CS. Human intestinal microbiota derived metabolism signature from a North American native botanical Oplopanax horridus with UPLC/Q-TOF-MS analysis. Biomed Chromatogr 2020; 34:e4911. [PMID: 32496571 DOI: 10.1002/bmc.4911] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 06/02/2020] [Indexed: 01/23/2023]
Abstract
Oplopanax horridus, widely distributed in North America, is an herbal medicine traditionally used by Pacific indigenous peoples for various medical conditions. After oral ingestion, constituents in O. horridus extract (OhE) could be converted to their metabolites by the enteric microbiome before absorption. In this study, in order to mimic gut environment, the OhE was biotransformed using the enteric microbiome of healthy human subjects. For accurate and reliable data collection with optimized approaches in sample preparation and analytical conditions, ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry were used to characterize parent constituents and their metabolites. In the extract, 20 parent compounds were identified including polyynes, sesquiterpenes, monoterpeondids, phenylpropanoids and phenolic acids. After the biotransformation, a total of 78 metabolites were identified, of which 37 belonged to polyynes metabolites. The common biotransformation pathways are hydroxylation, acetylization, methylation and demethylation. Based on the pathway distributions, the metabolism signature of OhE has been explored. The metabolism pathways of OhE compounds are dependent on their structural classifications and hydrophilic/hydrophobic properties. In summary, with comprehensive analysis, we systematically investigated human microbiome-derived OhE metabolites. The enteric microbial metabolism signature provides novel information for future effective use of O. horridus.
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Affiliation(s)
- Chong-Zhi Wang
- Tang Center for Herbal Medicine Research, and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA
| | - Jin-Yi Wan
- National Institute of Chinese Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Jingxuan Wan
- National Institute of Chinese Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Shilei Wang
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Yun Luo
- Tang Center for Herbal Medicine Research, and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA
| | - Jinxiang Zeng
- Tang Center for Herbal Medicine Research, and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA
| | - Haiqiang Yao
- Tang Center for Herbal Medicine Research, and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA
| | - Chun-Feng Zhang
- Tang Center for Herbal Medicine Research, and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA
| | - Qi-Hui Zhang
- Tang Center for Herbal Medicine Research, and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA
| | - Wamtinga Richard Sawadogo
- Tang Center for Herbal Medicine Research, and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA
| | - Ming Xu
- Tang Center for Herbal Medicine Research, and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA
| | - Wei Du
- Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA
| | - Lian-Wen Qi
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Ping Li
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Chun-Su Yuan
- Tang Center for Herbal Medicine Research, and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA.,Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, IL, USA
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Pathobiological and molecular connections involved in the high fructose and high fat diet induced diabetes associated nonalcoholic fatty liver disease. Inflamm Res 2020; 69:851-867. [DOI: 10.1007/s00011-020-01373-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 05/22/2020] [Accepted: 06/16/2020] [Indexed: 12/14/2022] Open
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Popescu RG, Voicu SN, Gradisteanu Pircalabioru G, Ciceu A, Gharbia S, Hermenean A, Georgescu SE, Panaite TD, Dinischiotu A. Effects of Dietary Inclusion of Bilberry and Walnut Leaves Powder on the Digestive Performances and Health of Tetra SL Laying Hens. Animals (Basel) 2020; 10:ani10050823. [PMID: 32397418 PMCID: PMC7278370 DOI: 10.3390/ani10050823] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 05/03/2020] [Accepted: 05/05/2020] [Indexed: 02/07/2023] Open
Abstract
Simple Summary In poultry, diet composition influences growth performance, egg production, as well as digestion. In this study, the effects of dietary additives obtained from bilberry and walnut leaves powder on the digestive performances of Tetra SL hens were evaluated by histologic and morphometric analyses of the intestinal mucosa as well as by the enzymatic activity measurements of alpha-amylase, invertase, maltase, and trypsin correlated with cecum microbiota. Abstract The purpose of this study was to examine the effects of dietary inclusion of two additives at the final concentration of 0.5% bilberry (E1) and 1% walnut (E2) leaves powder in the basal diet on digestive health of hens. A total number of 90 Tetra SL hens were divided into two experimental groups (E1 and E2) and one control group (C) consisting of 30 hens each. After four weeks, 10 hens of each group were sacrificed and tissue samples and intestinal content were taken from the duodenum, jejunum, and cecum in order to perform histological, enzymatic, and microbiota analyses. In groups E1 and E2, the histological analysis showed a significant increase of villus height, resulting probably in increased absorption of nutrients in duodenum and jejunum. A decrease in the specific activity of alpha-amylase and trypsin in E1 and E2 for both duodenum and jejunum compared to the control one was also recorded. In addition, the maltase and invertase specific activity in duodenum increased, a tendency that was kept for maltase but not for invertase in jejunum. The cecal microbiota of E1 and E2 individuals was characterized by an increase of Firmicutes and Lactobacilli and a decrease of Enterobacteriaceae. In conclusion, our results indicate that bilberry and walnut leaves additives in feed may improve the health status of the poultry gastrointestinal tract.
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Affiliation(s)
- Roua Gabriela Popescu
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania; (R.G.P.); (A.C.); (S.G.); (S.E.G.); (A.D.)
| | - Sorina Nicoleta Voicu
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania; (R.G.P.); (A.C.); (S.G.); (S.E.G.); (A.D.)
- Department of Pharmacy, Faculty of Pharmacy, Titu Maiorescu University, 004051 Bucharest, Romania
- Correspondence: ; Tel.: +40-21-318-1575
| | | | - Alina Ciceu
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania; (R.G.P.); (A.C.); (S.G.); (S.E.G.); (A.D.)
- Department of Experimental and Applied Biology, “Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 310414 Arad, Romania;
| | - Sami Gharbia
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania; (R.G.P.); (A.C.); (S.G.); (S.E.G.); (A.D.)
- Department of Experimental and Applied Biology, “Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 310414 Arad, Romania;
| | - Anca Hermenean
- Department of Experimental and Applied Biology, “Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 310414 Arad, Romania;
| | - Sergiu Emil Georgescu
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania; (R.G.P.); (A.C.); (S.G.); (S.E.G.); (A.D.)
| | - Tatiana Dumitra Panaite
- National Research and Development Institute for Animal Biology (IBNA Balotești), 077015 Ilfov, Romania;
| | - Anca Dinischiotu
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania; (R.G.P.); (A.C.); (S.G.); (S.E.G.); (A.D.)
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Consumption of salt leads to ameliorate symptoms of metabolic disorder and change of gut microbiota. Eur J Nutr 2020; 59:3779-3790. [DOI: 10.1007/s00394-020-02209-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 02/14/2020] [Indexed: 12/17/2022]
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Ghoshal UC, Goel A, Quigley EMM. Gut microbiota abnormalities, small intestinal bacterial overgrowth, and non-alcoholic fatty liver disease: An emerging paradigm. Indian J Gastroenterol 2020; 39:9-21. [PMID: 32291578 DOI: 10.1007/s12664-020-01027-w] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Evidence accumulates to implicate a role for the gut microbiota in non-alcoholic fatty liver disease (NAFLD)-a disorder that has reached almost epidemic proportions around the globe. For some time a disturbance in the gut microbiome, small intestinal bacterial overgrowth (SIBO), has been described among patients with liver disease, in general, and in the development and progression of NAFLD to nonalcoholic steatohepatitis (NASH), decompensated liver disease and hepatocellular cancer (HCC), in particular. More recently and permitted by the advent of high-throughput sequencing and allied molecular techniques, a much more detailed analysis of gut microbiota in NAFLD and NASH has become possible. In animal models, several mechanisms have been delineated which reveal how gut bacteria and their products could promote steatosis, hepatic inflammation, fibrosis, cirrhosis, and carcinogenesis. For understandable reasons evidence from human studies is less complete, but here again a plausible case is beginning to emerge to incriminate microbiota in NAFLD and NASH pathogenesis. Therapeutic interventions based on the modulation of the microbiome have been explored to some extent, but their application to everyday medical practice is still in the future.
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Affiliation(s)
- Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Amit Goel
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Eamonn M M Quigley
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India. .,Gastroenterology and Hepatology, Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College, 6550 Fannin St, SM 1201, Houston, TX, 77030, USA.
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48
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Du H, Zhao A, Wang Q, Yang X, Ren D. Supplementation of Inulin with Various Degree of Polymerization Ameliorates Liver Injury and Gut Microbiota Dysbiosis in High Fat-Fed Obese Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:779-787. [PMID: 31894986 DOI: 10.1021/acs.jafc.9b06571] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
The chain length of fructan determines its different physiological effects. This study is to explore the effects of low-performance inulin [LPI, degree of polymerization (DP) ≤ 9] and high-performance inulin (HPI, DP ≥ 23) on obesity-associated liver injury of high-fat diet (HFD) feeding mice and its underlying mechanism. Eight weeks of supplementation of C57BL/6J mice with HPI, relative to LPI (p < 0.05), caused the more efficient improvement against the HFD-induced liver insulin resistance through activating IRS1/PI3K/Akt pathway and reduced protein expressions of inflammatory factors nuclear factor-kappaB (NF-κB) and interleukin-6 (IL-6) in the liver. HPI exhibited the more positive effects on liver steatosis by inhibiting acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and sterol regulatory element binding protein 1 (SREBP1) in comparison with LPI (p < 0.05). HPI also increased acetic acid, propionic acid, and butyric acid levels in the colon of HFD-fed mice (p < 0.05). Compared to LPI, HPI feeding of HFD-fed mice led to the more effective decrease in the Firmicutes abundance from 72.1% to 34.5%, but a more significant increase in the Bacteroidetes population from 19.8 to 57.1% at the phyla level, and increased the abundance of Barnesiella, Bacteroides, and Parabacteroides at the genus level (p < 0.05). Depending on DP, HPI exerts the more positive regulation on liver injury and gut microbiota dysfunction than LPI.
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Affiliation(s)
- Haiping Du
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science , Shaanxi Normal University , Xi'an 710119 , China
| | - Aiqing Zhao
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science , Shaanxi Normal University , Xi'an 710119 , China
| | - Qi Wang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science , Shaanxi Normal University , Xi'an 710119 , China
| | - Xingbin Yang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science , Shaanxi Normal University , Xi'an 710119 , China
| | - Daoyuan Ren
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science , Shaanxi Normal University , Xi'an 710119 , China
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Huang J, Zhang W, Fan R, Liu Z, Huang T, Li J, Du T, Xiong T. Composition and functional diversity of fecal bacterial community of wild boar, commercial pig and domestic native pig as revealed by 16S rRNA gene sequencing. Arch Microbiol 2020; 202:843-857. [PMID: 31894392 DOI: 10.1007/s00203-019-01787-w] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Revised: 11/22/2019] [Accepted: 12/03/2019] [Indexed: 02/06/2023]
Abstract
The bacterial community in mammalian gastrointestinal tract is abundant and complex. To date, little is known about the gut microbiota of wild boar. This study aimed to investigate the fecal bacterial diversity of wild boar and compare with commercial pig and domestic native pig. The diet composition showed that the diets of wild boar, commercial pig and domestic native pig were different from each other. More than 1,760,000 quality-filtered sequences were obtained, and the results revealed distinct compositions and diversity of fecal microbiota in three groups. PCoA and NMDS analyses showed that fecal bacterial communities of wild boar, commercial pig and domestic native pig formed distinctly different clusters. Although the three groups shared a large size of OTUs comprising a core microbiota community, a strong distinction existed at family and genus levels. Ruminococcaceae, Prevotellaceae and Christensenellaceae were more abundant in the feces of wild boar than in domestic native pig and commercial pig. At the genus level, the proportion of unidentified Christensenellaceae was remarkably higher in wild boar group, while commercial pig and domestic native pig group had a higher abundance of Streptococcus and Lactobacillus. Tax4Fun predictions of metagenome function showed statistically significant differences in the functions of fecal microbiota in three groups. There were more bacteria genes with amino acid metabolism, cell growth and death, cell motility, energy metabolism, immune system and environmental adaptation observed in wild boar feces, while commercial pig feces contained more bacteria genes with carbohydrate metabolism, drug resistance, aging, infectious diseases, lipid metabolism, endocrine and metabolic diseases. These results indicated that the fecal microbial ecosystem of the wild boar is significantly different from that of domestic native pig and commercial pig, suggesting that diet is an important factor leading to differences in bacterial abundance and diversity in feces.
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Affiliation(s)
- Jinqing Huang
- State Key Laboratory of Food Science and Technology, No. 235 Nanjing East Road, Nanchang, 330047, Jiangxi, People's Republic of China.,School of Food Science and Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang, 330047, Jiangxi, People's Republic of China
| | - Wenjuan Zhang
- State Key Laboratory of Food Science and Technology, No. 235 Nanjing East Road, Nanchang, 330047, Jiangxi, People's Republic of China.,School of Food Science and Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang, 330047, Jiangxi, People's Republic of China
| | - Rong Fan
- Institute of Bioprocess and Pharmaceutical Technology, University of Applied Sciences, Wiesenstrasse 14, 35390, Giessen, Germany
| | - Zhanggen Liu
- State Key Laboratory of Food Science and Technology, No. 235 Nanjing East Road, Nanchang, 330047, Jiangxi, People's Republic of China.,School of Food Science and Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang, 330047, Jiangxi, People's Republic of China
| | - Tao Huang
- State Key Laboratory of Food Science and Technology, No. 235 Nanjing East Road, Nanchang, 330047, Jiangxi, People's Republic of China.,School of Food Science and Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang, 330047, Jiangxi, People's Republic of China
| | - Junyi Li
- State Key Laboratory of Food Science and Technology, No. 235 Nanjing East Road, Nanchang, 330047, Jiangxi, People's Republic of China.,School of Food Science and Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang, 330047, Jiangxi, People's Republic of China
| | - Tonghao Du
- State Key Laboratory of Food Science and Technology, No. 235 Nanjing East Road, Nanchang, 330047, Jiangxi, People's Republic of China.,School of Food Science and Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang, 330047, Jiangxi, People's Republic of China
| | - Tao Xiong
- State Key Laboratory of Food Science and Technology, No. 235 Nanjing East Road, Nanchang, 330047, Jiangxi, People's Republic of China. .,School of Food Science and Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang, 330047, Jiangxi, People's Republic of China.
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Abstract
AbstractDietary protein insufficiency has been linked to excessive TAG storage and non-alcoholic fatty liver disease (NAFLD) in developing countries. Hepatic TAG accumulation following a low-protein diet may be due to altered peroxisomal, mitochondrial and gut microbiota function. Hepatic peroxisomes and mitochondria normally mediate metabolism of nutrients to provide energy and substrates for lipogenesis. Peroxisome biogenesis and activities can be modulated by odd-chain fatty acids (OCFA) and SCFA that are derived from gut bacteria, for example, propionate and butyrate. Also produced during amino acid metabolism by peroxisomes and mitochondria, propionate and butyrate concentrations correlate inversely with risk of obesity, insulin resistance and NAFLD. In this horizon-scanning review, we have compiled available evidence on the effects of protein malnutrition on OCFA production, arising from loss in mitochondrial, peroxisomal and gut microbiota function, and its association with lipid accumulation in the liver. The methyl donor amino acid composition of dietary protein is an important contributor to liver function and lipid storage; the presence and abundance of dietary branched-chain amino acids can modulate the composition and metabolic activity of the gut microbiome and, on the other hand, can affect protective OCFA and SCFA production in the liver. In preclinical animal models fed with low-protein diets, specific amino acid supplementation can ameliorate fatty liver disease. The association between low dietary protein intake and fatty liver disease is underexplored and merits further investigation, particularly in vulnerable groups with dietary protein restriction in developing countries.
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