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

doi:10.1016/j.chom.2022.04.005

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

Cell Host Microbe. 2022 May 11;30(5):696-711.e5. doi: 10.1016/j.chom.2022.04.005.

Authors

Jumana Samara¹, Shirin Moossavi², Belal Alshaikh³, Van A Ortega⁴, Veronika Kuchařová Pettersen⁵, Tahsin Ferdous⁴, Suzie L Hoops⁶, Amuchou Soraisham³, Joseph Vayalumkal⁷, Deonne Dersch-Mills³, Jeffrey S Gerber⁸, Sagori Mukhopadhyay⁹, Karen Puopolo⁹, Thomas A Tompkins¹⁰, Dan Knights⁶, Jens Walter¹¹, Harish Amin³, Marie-Claire Arrieta¹²

Affiliations

¹ Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada; Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada; International Microbiome Centre, University of Calgary, Calgary, AB, Canada; Health Sciences Centre, Winnipeg, MB, Canada.
² Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada; Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada; International Microbiome Centre, University of Calgary, Calgary, AB, Canada; Microbiome and Microbial Ecology Interest Group (MMEIG), Universal Scientific Education and Research Network (USERN), Calgary, Canada.
³ Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada; Calgary Zone Section of Neonatology, Calgary, AB, Canada.
⁴ Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada; Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada; International Microbiome Centre, University of Calgary, Calgary, AB, Canada.
⁵ Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada; Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada; International Microbiome Centre, University of Calgary, Calgary, AB, Canada; Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.
⁶ Biotechnology Institute and Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN, USA.
⁷ Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.
⁸ Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
⁹ Newborn Care at Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
¹⁰ Lallemand Health Solutions, Montreal, QC, Canada.
¹¹ School of Microbiology, Department of Medicine, and APC Microbiome Ireland, University College Cork, Cork, Ireland.
¹² Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada; Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada; International Microbiome Centre, University of Calgary, Calgary, AB, Canada. Electronic address: [email protected].

PMID: 35550672
DOI: 10.1016/j.chom.2022.04.005

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.

Keywords: immune priming; maturation; microbiome; mycobiome; premature infant; probiotic.

Publication types

Randomized Controlled Trial

MeSH terms

Bifidobacterium
Ecosystem
Gastrointestinal Microbiome*
Humans
Infant
Infant, Extremely Premature
Infant, Newborn
Inflammation
Probiotics*