Novel <i>myo</i>-inositol to butyrate fermentation pathway in the prevalent human gut species <i>Dysosmobacter welbionis,</i> a bacterium associated with improved metabolic and liver health.
basic_science · Level V
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- Record sourced from PubMed, PMID 41500802.
- Also identified by DOI 10.1136/gutjnl-2025-336617.
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Abstract
<i>Dysosmobacter welbionis</i> 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 <i>myo</i>-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 <i>D. welbionis</i> in humans, and to elucidate its metabolic capacity to ferment <i>myo</i>-inositol into butyrate. We analysed several human cohorts for associations with liver health and evaluated <i>D. welbionis</i> J115<sup>T</sup> supplementation in a diet-induced steatosis mouse model. An antibody-guided anaerobic cell-sorting strategy enabled isolation of distinct strains. We combined <sup>13</sup>C-labelled inositol isotopes with NMR, mass spectrometry, genomics and proteomics. We found that <i>D. welbionis</i> and two related species (<i>D. hominis</i> and <i>D. segnis</i>) are prevalent gut bacteria in the human gut. <i>D. welbionis</i> abundance was reduced in MASLD across two cohorts and inversely correlated with fibrosis score in a third cohort. Treatment with <i>D. welbionis</i> J115<sup>T</sup> improved glycaemia and hepatic steatosis in high-fat diet fed mice. We identified a non-canonical <i>myo</i>-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 <i>myo-</i>inositol fermentation pathway. <i>D. welbionis</i> possesses a unique, conserved route to convert dietary <i>myo</i>-inositol into butyrate, distinguishing it from other commensals and supporting its potential as a next-generation probiotic for metabolic and liver health.