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      Bacteroides and NAFLD: pathophysiology and therapy

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          Abstract

          Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition observed globally, with the potential to progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. Currently, the US Food and Drug Administration (FDA) has not approved any drugs for the treatment of NAFLD. NAFLD is characterized by histopathological abnormalities in the liver, such as lipid accumulation, steatosis, hepatic balloon degeneration, and inflammation. Dysbiosis of the gut microbiota and its metabolites significantly contribute to the initiation and advancement of NAFLD. Bacteroides, a potential probiotic, has shown strong potential in preventing the onset and progression of NAFLD. However, the precise mechanism by which Bacteroides treats NAFLD remains uncertain. In this review, we explore the current understanding of the role of Bacteroides and its metabolites in the treatment of NAFLD, focusing on their ability to reduce liver inflammation, mitigate hepatic steatosis, and enhance intestinal barrier function. Additionally, we summarize how Bacteroides alleviates pathological changes by restoring the metabolism, improving insulin resistance, regulating cytokines, and promoting tight-junctions. A deeper comprehension of the mechanisms through which Bacteroides is involved in the pathogenesis of NAFLD should aid the development of innovative drugs targeting NAFLD.

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          Most cited references138

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          An obesity-associated gut microbiome with increased capacity for energy harvest.

          The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.
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            The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon.

            The microbiome is being characterized by large-scale sequencing efforts, yet it is not known whether it regulates host metabolism in a general versus tissue-specific manner or which bacterial metabolites are important. Here, we demonstrate that microbiota have a strong effect on energy homeostasis in the colon compared to other tissues. This tissue specificity is due to colonocytes utilizing bacterially produced butyrate as their primary energy source. Colonocytes from germfree mice are in an energy-deprived state and exhibit decreased expression of enzymes that catalyze key steps in intermediary metabolism including the TCA cycle. Consequently, there is a marked decrease in NADH/NAD(+), oxidative phosphorylation, and ATP levels, which results in AMPK activation, p27(kip1) phosphorylation, and autophagy. When butyrate is added to germfree colonocytes, it rescues their deficit in mitochondrial respiration and prevents them from undergoing autophagy. The mechanism is due to butyrate acting as an energy source rather than as an HDAC inhibitor. Copyright © 2011 Elsevier Inc. All rights reserved.
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              The abundance and variety of carbohydrate-active enzymes in the human gut microbiota.

              Descriptions of the microbial communities that live on and in the human body have progressed at a spectacular rate over the past 5 years, fuelled primarily by highly parallel DNA-sequencing technologies and associated advances in bioinformatics, and by the expectation that understanding how to manipulate the structure and functions of our microbiota will allow us to affect health and prevent or treat diseases. Among the myriad of genes that have been identified in the human gut microbiome, those that encode carbohydrate-active enzymes (CAZymes) are of particular interest, as these enzymes are required to digest most of our complex repertoire of dietary polysaccharides. In this Analysis article, we examine the carbohydrate-digestive capacity of a simplified but representative mini-microbiome in order to highlight the abundance and variety of bacterial CAZymes that are represented in the human gut microbiota.
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                Author and article information

                Contributors
                URI : http://loop.frontiersin.org/people/2521518/overviewRole: Role:
                Role: Role:
                Role: Role:
                URI : http://loop.frontiersin.org/people/782379/overviewRole: Role: Role:
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                20 March 2024
                2024
                : 15
                : 1288856
                Affiliations
                [1] 1Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo , Zhejiang, China
                [2] 2Cixi Biomedical Research Institute, Wenzhou Medical University, Ningbo , Zhejiang, China
                [3] 3Liver Diseases Institute, Ningbo No. 2 Hospital, Ningbo , Zhejiang, China
                [4] 4Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo , Zhejiang, China
                Author notes

                Edited by: Xiaozhen Jen Mou, Kent State University, United States

                Reviewed by: Jeehwan Oh, University of Wisconsin-Madison, United States

                Salvatore Pezzino, University of Catania, Italy

                *Correspondence: Hongshan Li, lihongshan_1982@ 123456126.com

                These authors have contributed equally to this work and share first authorship

                Article
                10.3389/fmicb.2024.1288856
                10988783
                38572244
                e8b234ed-aa49-41df-ac53-490651065245
                Copyright © 2024 Zhang, Zhou, He and Li.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 05 September 2023
                : 07 March 2024
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 138, Pages: 14, Words: 11361
                Funding
                The authors declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Zhejiang Provincial Natural Science Foundation of China under Grant No. LY23H290004, the Ningbo Natural Science Foundation, Project ID: 2022J242, the Major Special Science and Technology Project of Ningbo City (#2022Z128), National Administration of Traditional Chinese Medicine - Zhejiang Provincial Administration of Traditional Chinese Medicine Joint Construction Technology Plan (GZY-ZJ-KJ-23092), Zhejiang Province Traditional Chinese Medicine Science and Technology Plan (2022ZB332), and the Project of NINGBO Leading Medical and Health Discipline, Project Number: 2022Z01.
                Categories
                Microbiology
                Review
                Custom metadata
                Microbial Physiology and Metabolism

                Microbiology & Virology
                bacteroides,nafld,steatosis,liver inflammation,intestinal barrier
                Microbiology & Virology
                bacteroides, nafld, steatosis, liver inflammation, intestinal barrier

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