Cell
Volume 184, Issue 15, 22 July 2021, Pages 3884-3898.e11
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Article
Bifidobacteria-mediated immune system imprinting early in life

https://doi.org/10.1016/j.cell.2021.05.030Get rights and content
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Highlights

  • An ordered sequence of immune changes after birth driven by microbial interactions

  • Lack of gut bifidobacteria and HMO-utilization genes correlates with systemic inflammation

  • Feeding B. infantis EVC001 upregulates IFNβ and silences intestinal Th2 and Th17

  • EVC001-associated indole-3-lactic acid upregulates inhibitory galectin-1 in T cells

Summary

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
systems immunology
microbiome
immune system development
neonate
newborn immune systems
mass cytometry
metagenomics
transcriptome
neonatology

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