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Nature. 2018 Aug;560(7719):489-493. doi: 10.1038/s41586-018-0395-5. Epub 2018 Aug 8.

Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition.

Author information

1
Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
2
Institute of Microbiology and Epizootics, Department of Veterinary Medicine at the Freie Universität Berlin, Berlin, Germany.
3
Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
4
Institute of Clinical Molecular Biology (IKMB), Kiel University, Kiel, Germany.
5
Neuroscience Institute, Georgia State University, Atlanta, GA, USA.
6
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
7
Institute for Medical Microbiology, RWTH University Hospital Aachen, Aachen, Germany.
8
Division of Microbiology, University of Osnabrück, Osnabrück, Germany.
9
Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany.
10
Institute of Veterinary Pathology, Department of Veterinary Medicine at the Freie Universität Berlin, Berlin, Germany.
11
Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany. mhornef@ukaachen.de.
12
Institute for Medical Microbiology, RWTH University Hospital Aachen, Aachen, Germany. mhornef@ukaachen.de.

Abstract

Alterations in enteric microbiota are associated with several highly prevalent immune-mediated and metabolic diseases1-3, and experiments involving faecal transplants have indicated that such alterations have a causal role in at least some such conditions4-6. The postnatal period is particularly critical for the development of microbiota composition, host-microbe interactions and immune homeostasis7-9. However, the underlying molecular mechanisms of this neonatal priming period have not been defined. Here we report the identification of a host-mediated regulatory circuit of bacterial colonization that acts solely during the early neonatal period but influences life-long microbiota composition. We demonstrate age-dependent expression of the flagellin receptor Toll-like receptor 5 (TLR5) in the gut epithelium of neonate mice. Using competitive colonization experiments, we demonstrate that epithelial TLR5-mediated REG3γ production is critical for the counter-selection of colonizing flagellated bacteria. Comparative microbiota transfer experiments in neonate and adult wild-type and Tlr5-deficient germ-free mice reveal that neonatal TLR5 expression strongly influences the composition of the microbiota throughout life. Thus, the beneficial microbiota in the adult host is shaped during early infancy. This might explain why environmental factors that disturb the establishment of the microbiota during early life can affect immune homeostasis and health in adulthood.

PMID:
30089902
DOI:
10.1038/s41586-018-0395-5
[Indexed for MEDLINE]

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