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      Diet and gut microbiome in fatty liver and its associated liver cancer

      1 , 1
      Journal of Gastroenterology and Hepatology
      Wiley

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          <p class="first" id="d4932207e62">Non-alcoholic fatty liver disease (NAFLD) is the major cause of chronic liver disease worldwide as a consequence of a sedentary lifestyle and overnutrition. NAFLD could progress to non-alcoholic steatohepatitis (NASH), which may further develop to cirrhosis and hepatocellular carcinoma (HCC). The gut microbiome is one of the central regulators in host metabolism. Diet could change human gut microbiome rapidly and reproducibly and modulate several metabolic pathways. Both diet and gut microbiome dysbiosis are associated with NAFLD and its related HCC (NAFLD-HCC). Dietary cholesterol, fiber, fat, or carbohydrate could change the microbiome composition to contribute to the development of NASH and NAFLD-HCC. Hence, identification of elements of the gut-liver axis that are primarily damaged in NASH and NAFLD-HCC offers new possibility for therapeutic intervention. In this review, the roles of gut microbiome and microbial metabolites in the development and progression of NAFLD and NAFLD-HCC are first discussed. The impacts of different diet compositions including cholesterol, fiber, fat, and sugar on the gut microbiome that leads to predisposition to NASH and NAFLD-HCC are also explored. We summarized the article by discussing potential therapeutic implication of diet and microbiome modulation in fatty liver and liver cancer. </p>

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          Most cited references86

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          Diet rapidly and reproducibly alters the human gut microbiome

          Long-term diet influences the structure and activity of the trillions of microorganisms residing in the human gut 1–5 , but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here, we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila, and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale, and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals 2 , reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi, and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids, and the outgrowth of microorganisms capable of triggering inflammatory bowel disease 6 . In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.
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            Metabolic endotoxemia initiates obesity and insulin resistance.

            Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endotoxemia increased or decreased during the fed or fasted state, respectively, on a nutritional basis and that a 4-week high-fat diet chronically increased plasma LPS concentration two to three times, a threshold that we have defined as metabolic endotoxemia. Importantly, a high-fat diet increased the proportion of an LPS-containing microbiota in the gut. When metabolic endotoxemia was induced for 4 weeks in mice through continuous subcutaneous infusion of LPS, fasted glycemia and insulinemia and whole-body, liver, and adipose tissue weight gain were increased to a similar extent as in high-fat-fed mice. In addition, adipose tissue F4/80-positive cells and markers of inflammation, and liver triglyceride content, were increased. Furthermore, liver, but not whole-body, insulin resistance was detected in LPS-infused mice. CD14 mutant mice resisted most of the LPS and high-fat diet-induced features of metabolic diseases. This new finding demonstrates that metabolic endotoxemia dysregulates the inflammatory tone and triggers body weight gain and diabetes. We conclude that the LPS/CD14 system sets the tone of insulin sensitivity and the onset of diabetes and obesity. Lowering plasma LPS concentration could be a potent strategy for the control of metabolic diseases.
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              The Impact of Dietary Fiber on Gut Microbiota in Host Health and Disease

              Food is a primordial need for our survival and well-being. However, diet is not only essential to maintain human growth, reproduction, and health, but it also modulates and supports the symbiotic microbial communities that colonize the digestive tract-the gut microbiota. Type, quality, and origin of our food shape our gut microbes and affect their composition and function, impacting host-microbe interactions. In this review, we will focus on dietary fibers, which interact directly with gut microbes and lead to the production of key metabolites such as short-chain fatty acids, and discuss how dietary fiber impacts gut microbial ecology, host physiology, and health. Hippocrates' notion "Let food be thy medicine and medicine be thy food" remains highly relevant millennia later, but requires consideration of how diet can be used for modulation of gut microbial ecology to promote health.
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                Author and article information

                Contributors
                Journal
                Journal of Gastroenterology and Hepatology
                J of Gastro and Hepatol
                Wiley
                0815-9319
                1440-1746
                January 2022
                November 03 2021
                January 2022
                : 37
                : 1
                : 7-14
                Affiliations
                [1 ]State Key Laboratory of Digestive Disease, Institute of Digestive Disease and The Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute The Chinese University of Hong Kong Shatin Hong Kong China
                Article
                10.1111/jgh.15713
                34664301
                a3dcf749-ded6-40d0-af1c-a4f50e77e701
                © 2022

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                http://doi.wiley.com/10.1002/tdm_license_1.1

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