Intestinal microbiome adjusts the innate immune setpoint during colonization through negative regulation of MyD88

Nat Commun. 2018 Oct 5;9(1):4099. doi: 10.1038/s41467-018-06658-4.


Host pathways mediating changes in immune states elicited by intestinal microbial colonization are incompletely characterized. Here we describe alterations of the host immune state induced by colonization of germ-free zebrafish larvae with an intestinal microbial community or single bacterial species. We show that microbiota-induced changes in intestinal leukocyte subsets and whole-body host gene expression are dependent on the innate immune adaptor gene myd88. Similar patterns of gene expression are elicited by colonization with conventional microbiome, as well as mono-colonization with two different zebrafish commensal bacterial strains. By studying loss-of-function myd88 mutants, we find that colonization suppresses Myd88 at the mRNA level. Tlr2 is essential for microbiota-induced effects on myd88 transcription and intestinal immune cell composition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gastrointestinal Microbiome / immunology*
  • Genes, Reporter
  • Immunity, Innate*
  • Intestinal Mucosa / immunology*
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism*
  • Toll-Like Receptor 2 / metabolism
  • Transcriptome
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*


  • MyD88 protein, zebrafish
  • Myeloid Differentiation Factor 88
  • Toll-Like Receptor 2
  • Zebrafish Proteins