Familial transmission rather than defective innate immunity shapes the distinct intestinal microbiota of TLR-deficient mice
Open Access
- 23 July 2012
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 209 (8), 1445-1456
- https://doi.org/10.1084/jem.20120504
Abstract
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 ribosomal RNA 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 (WT) littermates demonstrated that the impact of TLR deficiency on the composition of the intestinal microbiota is minimal under homeostatic conditions and after recovery from antibiotic treatment. Thus, differences between TLR-deficient mouse colonies reflected long-term divergence of the microbiota after 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 account for marked compositional differences between WT and mutant mouse strains.Keywords
This publication has 43 references indexed in Scilit:
- Profound Alterations of Intestinal Microbiota following a Single Dose of Clindamycin Results in Sustained Susceptibility to Clostridium difficile-Induced ColitisInfection and Immunity, 2012
- Differential expression analysis for sequence count dataGenome Biology, 2010
- Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbationProceedings of the National Academy of Sciences of the United States of America, 2010
- Reproducible Community Dynamics of the Gastrointestinal Microbiota following Antibiotic PerturbationInfection and Immunity, 2009
- The Pervasive Effects of an Antibiotic on the Human Gut Microbiota, as Revealed by Deep 16S rRNA SequencingPLoS Biology, 2008
- Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficitsNature, 2008
- Molecular analysis of the bacterial microbiota in the human stomachProceedings of the National Academy of Sciences of the United States of America, 2006
- Diversity of the Human Intestinal Microbial FloraScience, 2005
- Effect of Antibiotic Therapy on the Density of Vancomycin-Resistant Enterococci in the Stool of Colonized PatientsThe New England Journal of Medicine, 2000
- Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple TestingJournal of the Royal Statistical Society: Series B (Methodological), 1995