SUMMARY
Immune-microbe interactions early in life influence an individual’s risk of developing allergies, asthma and some autoimmune disorders. Breastfeeding helps guide the development of healthy immune-microbe relationships, in part by providing nutrients to specialized microbes that in turn benefit the host and its developing immune system. Such bacteria having co-evolved with humans are associated with reduced risks of immune mediated diseases but are increasingly rare in modern societies. Here we map an immunological sequence of events, triggered by microbial colonization that distinguish children with different gut bacterial composition. Lack of bifidobacterial species is associated with elevated markers of intestinal inflammation and immune dysregulation and in a randomized trial of breastfed infants, the infant-adapted Bifidobacterium infantis EVC001 silenced intestinal Th2 and Th17 immune responses, while inducing IFNβ, and its metabolites skew T-cell polarization in vitro, from Th2 towards Th1, suggesting a healthier immune imprinting during the first critical months of life.
HIGHLIGHTS An ordered sequence of immune changes after birth, driven by microbial interactions
Low gut Bifidobacterium abundance is associated with markers of intestinal inflammation
Feeding B. infantis EVC001 silenced intestinal Th2 and Th17 but upregulates IFNβ
B. infantis EVC001 metabolites and/or enteric cytokines skew naïve T-cell polarization towards Th1 and away from Th2
Competing Interest Statement
PB, JM and TL are founders and shareholders of Cytodelics AB (Stockholm, Sweden). PB is an advisor to Scailyte AG (Zurich, Switzerland). RDM, SC, JP, HKB, SAF, and BMH are employees of Evolve BioSystems, a company focused on restoring the infant microbiome. JTS received funding to conduct the IMPRINT trial and AME received funding to assist in writing the manuscript. JBG is a co-founder of Evolve BioSystems. SAF and BMH serve as Adjunct Assistant Professors in Food Science & Technology Department, University of Nebraska Lincoln.
Footnotes
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