Effect of single versus multistrain probiotic in extremely preterm infants: a randomised trial.

Gayatri Athalye-Jape, Meera Esvaran, Sanjay Patole, Karen Simmer, Elizabeth Nathan, Dorota Doherty, Anthony Keil, Shripada Rao, Liwei Chen, Lakshmi Chandrasekaran, Chooi Kok, Stephan Schuster, Patricia Conway

Journal: BMJ open gastroenterology 2022;9(1):e000811

PMID: 35185013

Abstract

OBJECTIVE

Evidence indicates that multistrain probiotics benefit preterm infants more than single-strain (SS) probiotics. We assessed the effects of SS versus triple-strain (TS) probiotic supplementation (PS) in extremely preterm (EP) infants.

DESIGN

EP infants (gestational age (GA) <28 weeks) were randomly allocated to TS or SS probiotic, assuring blinding. Reference (REF) group was EP infants in the placebo arm of our previous probiotic trial. PS was commenced with feeds and continued until 37 weeks' corrected GA. Primary outcome was time to full feed (TFF: 150 mL/kg/day). Secondary outcomes included short-chain fatty acids and faecal microbiota collected at T1 (first week) and T2 (after 3 weeks of PS) using 16S ribosomal RNA gene sequencing.

RESULTS

173 EP (SS: 86, TS: 87) neonates with similar GA and birth weight (BW) were randomised. Median TFF was comparable (11 (IQR 8-16) vs 10 (IQR 8-16) days, p=0.92). Faecal propionate (SS, p<0.001, and TS, p=0.0009) and butyrate levels (TS, p=0.029) were significantly raised in T2 versus T1 samples. Secondary clinical outcomes were comparable. At T2, alpha diversity was comparable (p>0.05) between groups, whereas beta-diversity analysis revealed significant differences between PS and REF groups (both p=0.001). Actinobacteria were higher (both p<0.01), and Proteobacteria, Firmicutes and Bacteroidetes were lower in PS versus REF. Gammaproteobacteria, Clostridia and Negativicutes were lower in both PS versus REF.

CONCLUSION

TFF in EP infants was similar between SS and TS probiotics. Both probiotics were effective in reducing dysbiosis (higher bifidobacteria and lower Gammaproteobacteria). Long-term significance of increased propionate and butyrate needs further studies.

TRIAL REGISTRATION NUMBER

ACTRN 12615000940572.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Address: Neonatology directorate, King Edward Memorial Hospital for Women Perth, Subiaco, Western Australia, Australia [email protected].; Faculty of Science, University of New South Wales, Sydney, New South Wales, Australia.; Neonatal Clinical Care Unit, King Edward Memorial Hospital, Subiaco, Western Australia, Australia.; Biostatistics, Women and Infants Research Foundation Western Australia, Subiaco, Western Australia, Australia.; Microbiology, PathWest Laboratory Medicine Western Australia, Nedlands, Western Australia, Australia.; Neonatal Clinical Care Unit, Perth Children's Hospital, Nedlands, Western Australia, Australia.; Genomics and Bioinformatics, Nanyang Technological University, Singapore.
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