Abstract
Background
Uncertainty remains about the role of probiotics to prevent necrotising enterocolitis (NEC) some of which arises from the variety of probiotic interventions used in different trials, many with no prior evidence of potential efficacy. Mechanistic studies of intestinal barrier function embedded in a large probiotic trial could provide evidence about which properties of probiotics might be important for NEC prevention thus facilitating identification of strains with therapeutic potential.
Methods
Intestinal permeability, stool microbiota, SCFAs and mucosal inflammation were assessed from the second postnatal week in babies enrolled to a randomised controlled trial of B. breve BBG-001 (the PiPS trial). Results were compared by allocation and by stool colonisation with the probiotic.
Results
Ninety-four preterm babies were recruited across six nested studies. B. breve BBG-001 content was higher by allocation and colonisation; Enterobacteriaceae and acetic acid levels were higher by colonisation. No measure of intestinal barrier function showed differences. The PiPS trial found no evidence of efficacy to reduce NEC.
Conclusions
That the negative results of the PiPS trial were associated with failure of this probiotic to modify intestinal barrier function supports the possibility that the tests described here have the potential to identify strains to progress to large clinical trials.
Impact
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Uncertainty about the therapeutic role of probiotics to prevent necrotising enterocolitis is in part due to the wide range of bacterial strains with no previous evidence of efficacy used in clinical trials.
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We hypothesised that mechanistic studies embedded in a probiotic trial would provide evidence about which properties of probiotics might be important for NEC prevention.
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The finding that the probiotic strain tested, Bifidobacterium breve BBG-001, showed neither effects on intestinal barrier function nor clinical efficacy supports the possibility that these tests have the potential to identify strains to progress to large clinical trials.
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Acknowledgements
Our thanks are extended to Yakult Honsha European Research Centre for Microbiology ESV (YHER), Belgium for analysing faecal samples for both microbiota and short-chain fatty acids. YHER had no role in the data analyses and interpretation of the results presented in this manuscript. The interventions for the PiPS trial were provided without charge by Yakult Honsha Co. Ltd. (Tokyo, Japan) until the point of entry to the UK. The PiPS trial was funded by the UK National Institute for Health Research Health Technology Assessment Programme, project number 05/501/04. Simon Eaton acknowledges support from the NIHR Great Ormond Street Biomedical Research Centre. Special thanks are extended to Mr. Nik Hannay for creating the figure presented in this manuscript. This study was supported by a strategic Research Grant from Barts Charity (Ref: 719/1102).
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P.F. designed the study, performed laboratory analyses, analysed data and wrote the manuscript; M.W. designed the study, provided laboratory support and reviewed the data and manuscript; S.E., N.P. and R.H. performed laboratory analyses and reviewed the manuscript; A.A. assisted with clinical data collection and reviewed the manuscript; P.H. provided statistical advice and reviewed the manuscript; M.R.M. and K.C. designed the study and co-wrote the manuscript.
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Ethics approval was granted by the South London REC 2 Committee (Ref 10/H0802/40). Participants were recruited following informed written parental consent.
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Fleming, P., Wilks, M., Eaton, S. et al. Bifidobacterium breve BBG-001 and intestinal barrier function in preterm babies: Exploratory Studies from the PiPS Trial. Pediatr Res 89, 1818–1824 (2021). https://doi.org/10.1038/s41390-020-01135-5
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DOI: https://doi.org/10.1038/s41390-020-01135-5
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