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Novel -inositol to butyrate fermentation pathway in the prevalent human gut species a bacterium associated with improved metabolic and liver health.

Lee, Chi-Hsien;Bui, Thi Phuong Nam;Petitfils, Camille;Jian, Ching;Cani, Patrice D;et.al.
(2026) Gut — (2026)

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Authors
  • Lee, Chi-Hsienorcid-logoUCLouvain
    Co-first author
  • Bui, Thi Phuong Nam
    Co-first author
  • Co-first author
  • Jian, Chingorcid-logo
    Author
  • Wong, Giselle CUCLouvain
    Author
  • Puel, AnthonyUCLouvain
    Author
  • Delzenne, Nathalie Morcid-logoUCLouvain
    Author
  • Muccioli, Giulio Gorcid-logoUCLouvain
    Author
  • Author
  • Cani, Patrice Dorcid-logoUCLouvain
    Author
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Abstract
is a recently discovered butyrate producer whose presence in stool correlates with improved metabolic health. Whether its abundance is reduced in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) remains unknown. Mechanistic insight into its butyrate production from -inositol, a dietary compound from fruits, beans, grains and nuts with metabolic benefits, is also limited. To assess population-level distribution, relative abundance and strain diversity of in humans, and to elucidate its metabolic capacity to ferment -inositol into butyrate. We analysed several human cohorts for associations with liver health and evaluated J115 supplementation in a diet-induced steatosis mouse model. An antibody-guided anaerobic cell-sorting strategy enabled isolation of distinct strains. We combined C-labelled inositol isotopes with NMR, mass spectrometry, genomics and proteomics. We found that and two related species ( and ) are prevalent gut bacteria in the human gut. abundance was reduced in MASLD across two cohorts and inversely correlated with fibrosis score in a third cohort. Treatment with J115 improved glycaemia and hepatic steatosis in high-fat diet fed mice. We identified a non-canonical -inositol-to-butyrate fermentation pathway. 19 human strains were isolated, comparative genomics of 23 strains revealed an open pangenome (about 2100 core genes) including the full inositol fermentation pathway. possesses a unique, conserved route to convert dietary -inositol into butyrate, distinguishing it from other commensals and supporting its potential as a next-generation probiotic for metabolic and liver health.
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Citations

Lee, C.-H., Bui, T. P. N., Petitfils, C., Jian, C., Wong, G. C., Puel, A., Le Roy, T., Bellais, S., Ben Abdallah, B., Nehlich, M., Leicht, T., Jia, M., Hoyles, L., Federici, M., Fernández-Real, J. M., Burcelin, R., Dumas, M.-E., Delzenne, N. M., Clavel, T., et al. (2026). Novel -inositol to butyrate fermentation pathway in the prevalent human gut species a bacterium associated with improved metabolic and liver health. Gut. Published. https://doi.org/10.1136/gutjnl-2025-336617 (Original work published 2026)