Familial transmission rather than defective innate immunity shapes the distinct intestinal microbiota of TLR-deficient mice.

The intestinal microbiota contributes to the development of the immune system and, conversely, the immune system influences the composition of the microbiota. Toll-like receptors (TLRs) in the gut recognize bacterial ligands. Although TLR signaling represents a major arm of the innate immune system, the extent to which TLRs influence the composition of the intestinal microbiota remains unclear. We performed deep 16S rRNA sequencing to characterize the complex bacterial populations inhabiting the ileum and cecum of TLR and MyD88 deficient mice. The microbiota of MyD88 and TLR-deficient mouse colonies differed markedly, with each colony harboring distinct and distinguishable bacterial populations in the small and large intestine. Comparison of MyD88, TLR2, TLR4, TLR5 and TLR9 deficient mice and their respective wild type littermates demonstrated that the impact of TLR deficiency on the composition of the intestinal microbiota is minimal under homeostatic conditions and following recovery from antibiotic treatment. Thus, differences between TLR-deficient mouse colonies reflected long-term divergence of the microbiota following extended husbandry in isolation from each other. Long-term breeding of isolated mouse colonies results in changes of the intestinal microbiota that are communicated to offspring by maternal transmission, which accounts for marked compositional differences between wild type and mutant mouse strains.