Bifidobacteria-mediated immune system imprinting early in life

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


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bifidobacterium / physiology*
  • Biomarkers / metabolism
  • Breast Feeding
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Polarity
  • Cell Proliferation
  • Cytokines / metabolism
  • Feces / chemistry
  • Feces / microbiology
  • Galectin 1 / metabolism
  • Gastrointestinal Microbiome
  • Humans
  • Immune System / growth & development*
  • Immune System / microbiology*
  • Indoles / metabolism
  • Infant, Newborn
  • Inflammation / blood
  • Inflammation / genetics
  • Intestinal Mucosa / immunology
  • Metabolome
  • Milk, Human / chemistry
  • Oligosaccharides / metabolism
  • Th17 Cells / immunology
  • Th2 Cells / immunology
  • Water


  • Anti-Bacterial Agents
  • Biomarkers
  • Cytokines
  • Galectin 1
  • Indoles
  • Oligosaccharides
  • Water
  • indole-3-lactic acid