Journal article
Dietary fibre-adapted gut microbiome clears dietary fructose and reverses hepatic steatosis
Nature metabolism, Vol.7(9), pp.1801-1818
09/01/2025
DOI: 10.1038/s42255-025-01356-0
PMID: 40954286
Abstract
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 peroxidation. These multi-modal effects of inulin are transmittable by the gut microbiome, where Bacteroides acidifaciens acts as a key player. Thus, the gut microbiome, adapted to use inulin (a fructose polymer), efficiently catabolizes dietary monomeric fructose, thereby protecting the host. These findings provide a mechanism for how fibre can facilitate the gut microbiome to mitigate the host's exposure to harmful nutrients and disease progression.
Details
- Title: Subtitle
- Dietary fibre-adapted gut microbiome clears dietary fructose and reverses hepatic steatosis
- Creators
- Sunhee Jung - University of California, IrvineHosung Bae - University of California, IrvineWon-Suk Song - University of California, IrvineYujin Chun - University of California, IrvineJohnny Le - University of California, IrvineYasmine Alam - University of California, IrvineAmandine Verlande - University of California, IrvineSung Kook Chun - University of California, IrvineJoohwan Kim - University of California, IrvineMiranda E Kelly - University of California, IrvineMiranda L Lopez - University of California, IrvineSang Hee Park - University of California, IrvineDaniel Onofre - University of California, IrvineJongwon Baek - University of California, IrvineKi-Hong Jang - University of California, IrvineVarvara I Rubtsova - University of California, IrvineAlexis Anica - University of California, IrvineSelma Masri - University of California, IrvineGina Lee - University of California, IrvineCholsoon Jang - University of California, Irvine
- Resource Type
- Journal article
- Publication Details
- Nature metabolism, Vol.7(9), pp.1801-1818
- DOI
- 10.1038/s42255-025-01356-0
- PMID
- 40954286
- NLM abbreviation
- Nat Metab
- ISSN
- 2522-5812
- eISSN
- 2522-5812
- Grant note
- R01-AA029124 / U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01CA244519 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) K22-CA234399 / U.S. Department of Health & Human Services | National Institutes of Health (NIH) 2021R1A6A3A-14039681 / National Research Foundation of Korea (NRF) T32GM008620 / U.S. Department of Health & Human Services | National Institutes of Health (NIH) K22 CA234399 / NCI NIH HHS R21 AA030358 / NIAAA NIH HHS R01 CA244519 / NCI NIH HHS T32 GM008620 / NIGMS NIH HHS P30CA062203 / UC | UC Irvine | Chao Family Comprehensive Cancer Center (CFCCC)
- Language
- English
- Date published
- 09/01/2025
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985217035902771
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