Publikationsdatenbank

Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition (2018)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Fulde, Marcus (WE 7)

Sommer, Felix

Chassaing, Benoit

van Vorst, Kira (WE 7)

Dupont, Aline

Hensel, Michael

Basic, Marijana

Klopfleisch, Robert (WE 12)

Rosenstiel, Philip

Bleich, André

Bäckhed, Fredrik

Gewirtz, Andrew T

Hornef, Mathias W

Quelle

Nature : the international journal of science

Bandzählung: 560

Heftzählung: 7719

Seiten: 489 – 493

ISSN: 0028-0836

Sprache

Englisch

Verweise

DOI: 10.1038/s41586-018-0395-5

Pubmed: 30089902

Kontakt

Institut für Mikrobiologie und Tierseuchen

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51843 / 66949
mikrobiologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.