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Randomized Controlled Trial
. 2021 Jul 22;184(15):3884-3898.e11.
doi: 10.1016/j.cell.2021.05.030. Epub 2021 Jun 17.

Bifidobacteria-mediated immune system imprinting early in life

Bethany M Henrick  1 , Lucie Rodriguez  2 , Tadepally Lakshmikanth  2 , Christian Pou  2 , Ewa Henckel  3 , Aron Arzoomand  2 , Axel Olin  2 , Jun Wang  2 , Jaromir Mikes  2 , Ziyang Tan  2 , Yang Chen  2 , Amy M Ehrlich  4 , Anna Karin Bernhardsson  2 , Constantin Habimana Mugabo  2 , Ylva Ambrosiani  5 , Anna Gustafsson  6 , Stephanie Chew  4 , Heather K Brown  4 , Johann Prambs  4 , Kajsa Bohlin  6 , Ryan D Mitchell  4 , Mark A Underwood  7 , Jennifer T Smilowitz  8 , J Bruce German  8 , Steven A Frese  9 , Petter Brodin  10
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Free article
Randomized Controlled Trial

Bifidobacteria-mediated immune system imprinting early in life

Bethany M Henrick et al. Cell. .
Free article

Abstract

Immune-microbe interactions early in life influence the risk of allergies, asthma, and other inflammatory diseases. Breastfeeding guides healthier immune-microbe relationships by providing nutrients to specialized microbes that in turn benefit the host's immune system. Such bacteria have co-evolved with humans but are now increasingly rare in modern societies. Here we show that a lack of bifidobacteria, and in particular depletion of genes required for human milk oligosaccharide (HMO) utilization from the metagenome, is associated with systemic inflammation and immune dysregulation early in life. In breastfed infants given Bifidobacterium infantis EVC001, which expresses all HMO-utilization genes, intestinal T helper 2 (Th2) and Th17 cytokines were silenced and interferon β (IFNβ) was induced. Fecal water from EVC001-supplemented infants contains abundant indolelactate and B. infantis-derived indole-3-lactic acid (ILA) upregulated immunoregulatory galectin-1 in Th2 and Th17 cells during polarization, providing a functional link between beneficial microbes and immunoregulation during the first months of life.

Keywords: human immunology; immune system development; mass cytometry; metagenomics; microbiome; neonate; neonatology; newborn immune systems; systems immunology; transcriptome.

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Conflict of interest statement

Declaration of interests P.B., A.O., J.M., and T.L. are co-founders of Cytodelics AB (Stockholm, Sweden). P.B. is an advisor to Scailyte AG (Zurich, Switzerland) and Kancera AB (Stockholm, Sweden). R.D.M., S.C., J.P., H.K.B., S.A.F., and B.M.H. are employees of Evolve BioSystems. J.T.S. received funding to conduct the IMPRINT trial and A.M.E. received funding to assist in writing the manuscript. J.B.G. is a co-founder of Evolve BioSystems. S.A.F. and B.M.H. serve as adjunct assistant professors in the Food Science and Technology Department, University of Nebraska, Lincoln. P.B. and B.M.H. are co-inventors on a patent application related to this work.

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