ESPEYB16 14. Year in Science and Medicine 2019 (1) (18 abstracts)
14.11. Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition
Fulde M , Sommer F , Chassaing B , van Vorst K , Dupont A , Hensel M , Basic M , Klopfleisch R , Rosenstiel P , Bleich A , Backhed F , Gewirtz AT & Hornef MW
Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
To read the full abstract: Nature 2018;560:489–493.
This paper reports competitive gut colonization experiments in mice. Compared to adult mice, neonatal mice showed much higher expression of the flagellin receptor Tlr5 in their intestinal epithelial cells, and exposure to this protein during the first 2 weeks of life, before weaning, was crucial in determining lifelong gut microbiota composition with relevance to metabolic health.
TLR5 binds to flagellin, a protein that some pathogenic Salmonella bacteria use for motility; thereby TLR5 limits early-life colonization by such bacteria. Here, the authors show that, compared to normal wild-type mice, Tlr5-deficient neonatal mice have a higher rate of colonisation by flagellated Salmonella. These early differences lead to life-long ‘dysbiotic’ changes in gut microbiota, which are also associated with poorer metabolic health. Furthermore, by experimentally transferring the dysbiotic gut microbiota from these mice, they showed that transient early life expression of Tlr5 is crucial in determining the outcome. Normal wild-type pups, who express high levels of Tlr5, gradually eliminated the dysbiotic microbiota, whereas Tlr5-deficient pups and adult mice (both with low or absent Tlr5) retained high levels of dysbiotic microbiota.
These findings highlight a remarkable mechanism by which metabolic health can be programmed for the long-term by very short-term exposures interacting with genetic variation. There is much research interest in how gut microbiota is established and evolves with changes in diet in human infants. So far, there is no evidence that the marked gut microbiota differences seen between breastfed and formula fed infants persists after weaning. Possibly we will find such hypothesised persisting effects from other early life dietary exposures or gastro-intestinal infections, and their interactions with genotypes.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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