Clostridia from preterm infants metabolize human milk oligosaccharides to suppress pathobionts and modulate intestinal function in organoids

Chapman, Jonathan A., Masi, Andrea C., Beck, Lauren C., Watson, Hannah, Young, Gregory R., Browne, Hilary P., Shao, Yan, Kiu, Raymond, Nelson, Andrew, Doyle, Jennifer A., Palmowski, Pawel, Lengyel, Márton, Connolly, James P. R., Lamb, Christopher A., Porter, Andrew, Lawley, Trevor D., Hall, Lindsay J., Embleton, Nicholas D., Perry, John D., Berrington, Janet E. and Stewart, Christopher J. (2026) Clostridia from preterm infants metabolize human milk oligosaccharides to suppress pathobionts and modulate intestinal function in organoids. Nature Microbiology, 11. pp. 940-959. ISSN 2058-5276

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Abstract

Infant gut microbiome development is strongly impacted by breastmilk and human milk oligosaccharides (HMOs), which can protect preterm infants against pathologies including necrotizing enterocolitis. 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 Clostridium species isolated from preterm infants (born at <32 weeks gestation), in particular Clostridium perfringens lacking the toxin perfringolysin O (PfoA), metabolized HMOs. Clostridium species produced beneficial metabolites including short-chain fatty acids and tryptophan catabolites at higher quantities than Bifidobacterium species in vitro. Cell-free supernatant from C. perfringens 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 pfoA−C. perfringens strains could contribute to healthy infant gut development.

Item Type:	Article
Additional Information:	Data availability: The RNA-seq data have been deposited in the Sequencing Read Archive (SRA) under study accession number PRJNA1214204. The proteomics datasets are deposited in MassIVE under submission ID MSV000096907. Sequencing reads for de novo genomes have been deposited in the European Nucleotide Archive (ENA) under accession number ERP187615. Source data are provided with this paper.
Uncontrolled Keywords:	microbiology,immunology,applied microbiology and biotechnology,genetics,microbiology (medical),cell biology ,/dk/atira/pure/subjectarea/asjc/2400/2404
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	09 Apr 2026 15:30
Last Modified:	09 Apr 2026 15:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/102740
DOI:	10.1038/s41564-026-02297-4

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