biostudies-literatureJung SU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)National Research Foundation of Korea (NRF)UC | UC Irvine | Chao Family Comprehensive Cancer Center (CFCCC)Ministry of Health and Welfare (Ministry of Health, Welfare and Family Affairs)NCI NIH HHSU.S. Department of Health & Human Services | National Institutes of Health (NIH)American Diabetes Association (ADA)1801-1818https://www.ebi.ac.uk/biostudies/studies/S-EPMC12460171biostudies-literatureUnknown7(9)Excessive consumption of the simple sugar fructose, which induces excessive hepatic lipogenesis and gut dysbiosis, is a risk factor for cardiometabolic diseases. Here we show in male mice that the gut microbiome, when adapted to dietary fibre inulin, catabolizes dietary fructose and mitigates or reverses insulin resistance, hepatic steatosis and fibrosis. Specifically, inulin supplementation, without affecting the host's small intestinal fructose catabolism, promotes the small intestinal microbiome to break down incoming fructose, thereby decreasing hepatic lipogenesis and fructose spillover to the colonic microbiome. Inulin also activates hepatic de novo serine synthesis and cystine uptake, augmenting glutathione production and protecting the liver from fructose-induced lipid peroxidationNature metabolismDietary fibre-adapted gut microbiome clears dietary fructose and reverses hepatic steatosis.PMC12460171RS-2024-00411784021R1A6A3A140391322021R1A6A3A-14039681HI19C1352F31DK134173T32GM008620R21-AA030358K22-CA234399R01-AA029124R01CA244519P30 CA06220311-23-PDF-03R01CA259370P30CA062203Bae HJang CChun SKMasri SLe JBaek JSong WSKim JOnofre DVerlande ALee GLopez MLChun YRubtsova VIAlam YKelly MEPark SHAnica AJung SJang KHfalseDietary fibre-adapted gut microbiome clears dietary fructose and reverses hepatic steatosis.Excessive consumption of the simple sugar fructose, which induces excessive hepatic lipogenesis and gut dysbiosis, is a risk factor for cardiometabolic diseases. Here we show in male mice that the gut microbiome, when adapted to dietary fibre inulin, catabolizes dietary fructose and mitigates or reverses insulin resistance, hepatic steatosis and fibrosis. Specifically, inulin supplementation, without affecting the host's small intestinal fructose catabolism, promotes the small intestinal microbiome to break down incoming fructose, thereby decreasing hepatic lipogenesis and fructose spillover to the colonic microbiome. Inulin also activates hepatic de novo serine synthesis and cystine uptake, augmenting glutathione production and protecting the liver from fructose-induced lipid peroxidation2025-01-01T00:00:00Z2025 Sep2026-06-03T19:37:55.894Z2026-04-30T03:12:27.473ZS-EPMC124601714095428610.1038/s42255-025-01356-0