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HMO metabolism in bifidobacteria is well characterized and linked to health outcomes, but the scope of HMO-utilizing species remains unclear. Here, using a combination of genomics, proteomics and metabolomics, we show that\n                    <jats:italic>Clostridium<\/jats:italic>\n                    species isolated from preterm infants (born at &lt;32\u2009weeks gestation), in particular\n                    <jats:italic>Clostridium perfringens<\/jats:italic>\n                    lacking the toxin perfringolysin O (PfoA), metabolized HMOs.\n                    <jats:italic>Clostridium<\/jats:italic>\n                    species produced beneficial metabolites including short-chain fatty acids and tryptophan catabolites at higher quantities than\n                    <jats:italic>Bifidobacterium<\/jats:italic>\n                    species in vitro. Cell-free supernatant from\n                    <jats:italic>C. perfringens<\/jats:italic>\n                    was non-toxic to colonic cell lines, promoted the growth of commensal bifidobacteria and inhibited growth of pathobionts isolated from the preterm infant gut in vitro. It also suppressed inflammation in preterm-derived intestinal organoids. These findings expand our understanding of HMO-metabolizing microbes and suggest that\n                    <jats:italic>pfoA<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>C. perfringens<\/jats:italic>\n                    strains could contribute to healthy infant gut development.\n                  <\/jats:p>","DOI":"10.1038\/s41564-026-02297-4","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T10:02:13Z","timestamp":1773655333000},"page":"940-959","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Clostridia from preterm infants metabolize human milk oligosaccharides to suppress pathobionts and modulate intestinal function in organoids"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1068-8278","authenticated-orcid":false,"given":"Jonathan A.","family":"Chapman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea C.","family":"Masi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren C.","family":"Beck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Watson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory R.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1305-2470","authenticated-orcid":false,"given":"Hilary P.","family":"Browne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8662-0504","authenticated-orcid":false,"given":"Yan","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4483-1215","authenticated-orcid":false,"given":"Raymond","family":"Kiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Doyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Palmowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rton","family":"Lengyel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0394-3413","authenticated-orcid":false,"given":"James P. 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N.D.E. and J.E.B. declare research funding paid to their institution from Prolacta Biosciences, NeoKare UK and Danone Early Life Nutrition for grants between 2016\u20132022. N.D.E. declares lecture honoraria from Nestle Nutrition Institute and Abbot Nutrition and declares providing consultancy advice to legal firms involved in class action for infants developing NEC; all honoraria and consultancy fees were donated to charity. C.J.S. declares lecture honoraria from Nestl\u00e9 Nutrition Institute. T.D.L. is the co-founder and CSO of Microbiotica. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}