Human milk oligosaccharide metabolism by Clostridium species suppresses inflammation and pathogen growth

Chapman, J. A.; Masi, A. C.; Beck, L. C.; Watson, H.; Young, G. R.; Browne, H. P.; Shao, Y.; Kiu, R.; Nelson, A.; Doyle, J. A.; Palmowski, P.; Lengyel, M.; Connolly, J. P. R.; Lamb, C. A.; Porter, A.; Lawley, T. D.; Hall, L. J.; Embleton, N. D.; Perry, J. D.; Berrington, J. E.; Stewart, C. J.

doi:10.1101/2025.01.21.633585

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bioRxiv · 10.1101/2025.01.21.633585

Human milk oligosaccharide metabolism by Clostridium species suppresses inflammation and pathogen growth

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Abstract

Gut microbiome development is strongly impacted by breastmilk and human milk oligosaccharides (HMOs), with short- and long-term health implications. HMO metabolism is best characterised within bifidobacteria, but the full range of other HMO-utilising species remains unknown. This study examined HMO-utilising bacteria that colonise preterm infants (born <32 weeks gestation), their role in microbiome modulation, and their effects on intestinal barrier function. We found that infant-derived Clostridium perfringens, and three other Clostridium species, metabolise HMOs, producing short chain fatty acids, tryptophan catabolites, and other metabolites known to improve host health. C. perfringens inhibited pathobiont growth and supressed inflammation in preterm-derived intestinal organoids. These findings suggest a previously unrecognised role for C. perfringens, specifically those lacking the perfringolysin O gene, in promoting healthy gut development during infancy.

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Chapman, J. A., Masi, A. C., Beck, L. C., Watson, H., Young, G. R., Browne, H. P., Shao, Y., Kiu, R., Nelson, A., Doyle, J. A., Palmowski, P., Lengyel, M., Connolly, J. P. R., Lamb, C. A., Porter, A., Lawley, T. D., Hall, L. J., Embleton, N. D., Perry, J. D., Berrington, J. E., Stewart, C. J.. 2025-01-21. Human milk oligosaccharide metabolism by Clostridium species suppresses inflammation and pathogen growth. https://doi.org/10.1101/2025.01.21.633585

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