Supplementation with a probiotic mixture accelerates gut microbiome maturation and reduces intestinal inflammation in extremely preterm infants

Jumana Samara, Shirin Moossavi, Belal Alshaikh, Van A. Ortega, Veronika Kuchařová Pettersen, Tahsin Ferdous, Suzie L. Hoops, Amuchou Soraisham, Joseph Vayalumkal, Deonne Dersch-Mills, Jeffrey S. Gerber, Sagori Mukhopadhyay, Karen Puopolo, Thomas A. Tompkins, Dan Knights, Jens Walter, Harish Amin, Marie Claire Arrieta

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Probiotics are increasingly administered to premature infants to prevent necrotizing enterocolitis and neonatal sepsis. However, their effects on gut microbiome assembly and immunity are poorly understood. Using a randomized intervention trial in extremely premature infants, we tested the effects of a probiotic product containing four strains of Bifidobacterium species autochthonous to the infant gut and one Lacticaseibacillus strain on the compositional and functional trajectory of microbiome. Daily administration of the mixture accelerated the transition into a mature, term-like microbiome with higher stability and species interconnectivity. Besides infant age, Bifidobacterium strains and stool metabolites were the best predictors of microbiome maturation, and structural equation modeling confirmed probiotics as a major determinant for the trajectory of microbiome assembly. Bifidobacterium-driven microbiome maturation was also linked to an anti-inflammatory intestinal immune milieu. This demonstrates that Bifidobacterium strains are ecosystem engineers that lead to an acceleration of microbiome maturation and immunological consequences in extremely premature infants.

Original languageEnglish (US)
Pages (from-to)696-711.e5
JournalCell Host and Microbe
Volume30
Issue number5
DOIs
StatePublished - May 11 2022

Bibliographical note

Funding Information:
The authors would like to acknowledge study participants and their families for their support to research, as well as NICU nurses for their effort in sample collection and communication with the study group. The following collaborators supported clinical and laboratory aspects of this research: Rachel Sheinfeld, Erik van Tilburg Bernardes, Mackenzie Gutierrez, Kristen Kalbfleisch, Julia Gorospe, Amanda Piano, Dr. Neha Bansal, Marija Drikic, and Ryan Groves. This work was supported by funds from the Cumming School of Medicine, the Alberta Children Hospital Research Institute, the Snyder Institute of Chronic Diseases, the Canadian Institutes for Health Research. The International Microbiome Center is supported by the Cumming School of Medicine, University of Calgary, Western Economic Diversification and Alberta Economic Development, and Trade, Canada. S. Moossavi is supported by CIHR and Killam Postdoctoral Fellowship. V.A.O. is supported by a MITACS Elevate Fellowship. J.W. acknowledges support by Science Foundation Ireland (SFI) through an SFI Professorship (19/RP/6853) and a Centre award (APC/SFI/12/RC/2273_P2) to the APC Microbiome Ireland. H.A. B.A. A.S. J.V. and D.D.-M. contributed to the design of the premature RCT study. J.S. and B.A. monitored the clinical trial. J.S. communicated with study participant families, conducted study interviews, and compilated all clinical data. J.S. V.K.P. and V.A.O. prepared all the samples for sequencing and metabolomics analysis. J.S. carried out qPCR analysis. S. Moossavi, J.S. and M.-C.A. analyzed the 16S and ITS2 sequences. S. Moossavi, J.S. V.A.O. and V.K.P. analyzed the metabolomics data. S. Moossavi and T.F. carried out statistical analysis. V.A.O. performed immune and protein determination assays. S. Moossavi and M.-C.A. created the paper figures. T.A.T. provided probiotic strains and with J.W. guidance on qPCR protocol. S.L.H. D.K. J.S.G. S. Mukhopadhyay, and K.P. provided the 16S sequences from the MAGIC Study. M.-C.A. S. Moossavi, J.S. and J.W. contributed to data interpretation and writing the first and subsequent drafts of the manuscript. All authors edited the manuscript and contributed extensively to the work presented here. T.A.T. was the Research Director at Lallemand Health Solutions, the manufacturers of FloraBABY. The other authors declare no competing interests.

Funding Information:
The authors would like to acknowledge study participants and their families for their support to research, as well as NICU nurses for their effort in sample collection and communication with the study group. The following collaborators supported clinical and laboratory aspects of this research: Rachel Sheinfeld, Erik van Tilburg Bernardes, Mackenzie Gutierrez, Kristen Kalbfleisch, Julia Gorospe, Amanda Piano, Dr. Neha Bansal, Marija Drikic, and Ryan Groves. This work was supported by funds from the Cumming School of Medicine , the Alberta Children Hospital Research Institute , the Snyder Institute of Chronic Diseases , the Canadian Institutes for Health Research . The International Microbiome Center is supported by the Cumming School of Medicine, University of Calgary , Western Economic Diversification and Alberta Economic Development , and Trade, Canada. S. Moossavi is supported by CIHR and Killam Postdoctoral Fellowship. V.A.O. is supported by a MITACS Elevate Fellowship. J.W. acknowledges support by Science Foundation Ireland (SFI) through an SFI Professorship ( 19/RP/6853 ) and a Centre award ( APC/SFI/12/RC/2273_P2 ) to the APC Microbiome Ireland .

Publisher Copyright:
© 2022 Elsevier Inc.

Keywords

  • immune priming
  • maturation
  • microbiome
  • mycobiome
  • premature infant
  • probiotic

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