{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T19:41:58Z","timestamp":1784230918186,"version":"3.55.0"},"reference-count":42,"publisher":"American Society for Clinical Investigation","issue":"12","funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["Grant-in-Aid for Scientific Research 16K09374"],"award-info":[{"award-number":["Grant-in-Aid for Scientific Research 16K09374"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Foundation for Advancement of International Science","award":["JPMJPR1537"],"award-info":[{"award-number":["JPMJPR1537"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,6,21]]},"abstract":"<jats:p>The gut-liver axis is of clinical importance as a potential therapeutic target in a wide range of liver diseases; however, the mechanisms underlying interactions between microbial products and immune responses in the liver remain unknown. In this study, we demonstrated that IL-10\u2013producing macrophages contribute to immune tolerance in the inflamed liver under intestinal barrier disruption in a murine tandem model of dextran sulfate sodium (DSS) colitis and concanavalin A (Con A) hepatitis. Intestinal barrier disruption protected mice from subsequent liver injury, and the severity of colitis directly affected susceptibility to such injury. The protective effect of DSS\u2013Con A was canceled in gut-sterilized mice, suggesting that gut microbiota play a substantial role in this process. Altered gut microbiota and their metabolites, along with a disrupted intestinal barrier, directly gave rise to immunological permissiveness in the inflamed liver. We identified 1-methylnicotinamide (1-MNA) as a candidate metabolite capable of suppressing liver injury with the potential to induce IL-10\u2013producing macrophages. Consistently, expression of nicotinamide N-methyltransferase, which converts nicotinamide to 1-MNA, was upregulated in the liver of DSS\u2013Con A mice, and this effect was abrogated by gut sterilization. Collectively, our results provide a mechanistic insight into the regulation of immunological balance in the liver via the gut-liver axis.<\/jats:p>","DOI":"10.1172\/jci.insight.91980","type":"journal-article","created":{"date-parts":[[2018,6,20]],"date-time":"2018-06-20T11:01:31Z","timestamp":1529492491000},"source":"Crossref","is-referenced-by-count":32,"title":["Intestinal barrier regulates immune responses in the liver via IL-10\u2013producing macrophages"],"prefix":"10.1172","volume":"3","author":[{"given":"Nobuhito","family":"Taniki","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinanomachi, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiro","family":"Nakamoto","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinanomachi, 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