Strain-specific impacts of probiotics are a significant driver of gut microbiome development in very preterm infants

Beck, Lauren C., Masi, Andrea C., Young, Greg, Vatanen, Tommi, Lamb, Christopher A., Smith, Rachel, Coxhead, Jonathan, Butler, Alana, Marsland, Benjamin J., Embleton, Nicholas D., Berrington, Janet E. and Stewart, Christopher J. (2022) Strain-specific impacts of probiotics are a significant driver of gut microbiome development in very preterm infants. Nature Microbiology, 7 (10). pp. 1525-1535. ISSN 2058-5276

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The development of the gut microbiome from birth plays important roles in short- and long-term health, but factors influencing preterm gut microbiome development are poorly understood. In the present study, we use metagenomic sequencing to analyse 1,431 longitudinal stool samples from 123 very preterm infants (<32 weeks’ gestation) who did not develop intestinal disease or sepsis over a study period of 10 years. During the study period, one cohort had no probiotic exposure whereas two cohorts were given different probiotic products: Infloran (Bifidobacterium bifidum and Lactobacillus acidophilus) or Labinic (B. bifidum, B. longum subsp. infantis and L. acidophilus). Mothers’ own milk, breast milk fortifier, antibiotics and probiotics were significantly associated with the gut microbiome, with probiotics being the most significant factor. Probiotics drove microbiome transition into different preterm gut community types (PGCTs), each enriched in a different Bifidobacterium sp. and significantly associated with increased postnatal age. Functional analyses identified stool metabolites associated with PGCTs and, in preterm-derived organoids, sterile faecal supernatants impacted intestinal, organoid monolayer, gene expression in a PGCT-specific manner. The present study identifies specific influencers of gut microbiome development in very preterm infants, some of which overlap with those impacting term infants. The results highlight the importance of strain-specific differences in probiotic products and their impact on host interactions in the preterm gut.

Item Type: Article
Additional Information: Funding information: We thank the NICU staff involved in the sample collection, particularly J. Groombridge. We thank the families for their willingness to help and support research. We also thank D. Smith, K. Hoffman, M. Wong and J. Petrosino (Baylor College of Medicine) for support with bioinformatic processing of raw data. This work was supported by the Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and The Royal Society (grant no. 221745/Z/20/Z), a Newcastle University Academic career Track Fellowship and the 2021 Lister Institute Prize Fellow Award. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any author-accepted manuscript version arising from this submission. Astarte Medical provided funding for stool sample retrieval and shipment for metagenomic sequencing. Tiny Lives supported set-up of the initial study and the biobanking fees. The funders played no part in the study design, analysis, interpretation or reporting.
Subjects: C500 Microbiology
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Elena Carlaw
Date Deposited: 11 Nov 2022 16:25
Last Modified: 11 Nov 2022 16:30

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