Abstract
Objective
To evaluate whether probiotic supplementation attenuates gut-dysbiosis in neonates with congenital gastrointestinal surgical conditions (CGISC).
Methods
Sixty-one neonates (≥35 weeks gestation) with CGISC were randomised to receive daily supplementation with a triple-strain bifidobacterial probiotic (n = 30) or placebo (n = 31) until discharge. Stool microbiota was analysed using 16S ribosomal RNA gene sequencing on samples collected before (T1), 1 week (T2), and 2 weeks (T3) after supplementation and before discharge (T4). The primary outcome was the sum of the relative abundance of potentially pathogenic families of Clostridiaceae, Enterobacteriaceae, Enterococcaceae, Pseudomonaceae, Staphylococcaeae, Streptococcaceae, and Yersiniaceae at T3.
Results
The median gestational age [38 weeks (IQR: 37.1–38.9)] was similar in both groups. The probiotic group had lower rates of caesarean deliveries (40% versus 70%, p = 0.02). The relative abundance of potentially pathogenic families was lower in the probiotic group compared to placebo at T3 [(median: 50.4 (IQR: 26.6–67.6) versus 67.1 (IQR: 50.9–96.2); p = 0.04). Relative abundance of Bifidobacteriaceae was higher in the probiotic group at T3 [(median: 39.8 (IQR: 24.9–52.1) versus 0.03 (IQR 0.02–2.1); p < 0.001). Stratified analysis continued to show a higher abundance of Bifidobacteriaceae in the probiotic group, irrespective of the mode of delivery.
Conclusions
Probiotic supplementation attenuated gut dysbiosis in neonates with CGISC.
Trial registration
http://www.anzctr.org.au (ACTRN12617001401347).
Impact
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Probiotic supplementation attenuates gut dysbiosis and improves stool short-chain fatty acid levels in neonates with congenital gastrointestinal surgical conditions.
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This is the second pilot RCT of probiotic supplementation in neonates with congenital gastrointestinal conditions.
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These findings will pave the way for conducting multicentre RCTs in this area.
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Acknowledgements
We sincerely thank the following: Dr. Fumiaki Abe and Dr. Noriyuki Iwabuchi of Morinaga Milk Industry Co., Ltd, Japan, for providing trial supplements free of cost. Ms. Margaret Shave and Ms. Thanh Tan for help with receiving the trial supplements, generating random sequence numbers, providing trial supplements for administration to study infants, and for maintaining audits. Members of the Data Safety and Monitoring Committee: Prof. Tobias Strunk (neonatologist) and Mr. Naeem Samnakay (paediatric surgeon). Medical scientific staff at PathWest Laboratory Medicine WA for performing microbial analysis of sachets. The nursing staff at Perth Children’s Hospital for collecting stool samples and administering trial supplements to study infants. Mr. Damber Shrestha for providing data from the neonatal database. Ms. Emma Anderton, Ms. Julie Hibbert, and Ms. Jamee Murdoch for processing the stool samples and storing them in a deep freezer at −80 °C. Ms. Yen Kok for helping with organising the shipment of stool samples to the lab at the University of New South Wales. Centre for Neonatal Research and Education, Neonatal Directorate, King Edward Memorial Hospital for Women, Western Australia for providing funds. Parents of study infants for providing informed consent for participation in the RCT. Study infants for participating in the RCT. Centre for Neonatal Research and Education, Neonatal Directorate, Child and Adolescent Health Service, Western Australia.
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Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data, drafting the article or revising it critically for important intellectual content, and final approval of the version to be published: S.C.R., M.E., L.C., A.D.K., I.J.G., K.N.S., B.W., P.L.C., and S.K.P.
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Rao, S., Esvaran, M., Chen, L. et al. Probiotic supplementation in neonates with congenital gastrointestinal surgical conditions: a pilot randomised controlled trial. Pediatr Res 92, 1122–1131 (2022). https://doi.org/10.1038/s41390-021-01884-x
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DOI: https://doi.org/10.1038/s41390-021-01884-x
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