{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T18:21:31Z","timestamp":1789064491072,"version":"build-2803163510"},"reference-count":75,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,2]],"date-time":"2022-10-02T00:00:00Z","timestamp":1664668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Global lifestyle changes have led to an increased incidence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), requiring further in-depth research to understand the mechanisms and develop new therapeutic strategies. In particular, high-fat and high-fructose diets have been shown to increase intestinal permeability, which can expose the liver to endotoxins. Indeed, accumulating evidence points to a link between these liver diseases and the intestinal axis, including dysbiosis of the gut microbiome and leaky-gut syndrome. Here, we review the mechanisms contributing to these links between the liver and small intestine in the pathogenesis of NAFLD\/NASH, focusing on the roles of intestinal microbiota and their metabolites to influence enzymes essential for proper liver metabolism and function. Advances in next-generation sequencing technology have facilitated analyses of the metagenome, providing new insights into the roles of the intestinal microbiota and their functions in physiological and pathological mechanisms. This review summarizes recent research linking the gut microbiome to liver diseases, offering new research directions to elucidate the detailed mechanisms and novel targets for treatment and prevention.<\/jats:p>","DOI":"10.3390\/ijms231911689","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T22:19:27Z","timestamp":1665267567000},"page":"11689","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Current Research on the Pathogenesis of NAFLD\/NASH and the Gut\u2013Liver Axis: Gut Microbiota, Dysbiosis, and Leaky-Gut Syndrome"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7240-4851","authenticated-orcid":false,"given":"Takashi","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michihiro","family":"Iwaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6263-1436","authenticated-orcid":false,"given":"Atsushi","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asako","family":"Nogami","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Yoneda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1146\/annurev-immunol-051116-052415","article-title":"Immune responses in the liver","volume":"36","author":"Kubes","year":"2018","journal-title":"Annu. 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