The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

Hughes, Kevin R., Schofield, Zoe, Dalby, Matthew J., Caim, Shabhonam, Chalklen, Lisa, Bernuzzi, Federico, Alcon-Giner, Cristina, Le Gall, Gwénaëlle ORCID:, Watson, Alastair J.M. ORCID: and Hall, Lindsay J. ORCID: (2020) The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding. FASEB Journal, 34 (5). pp. 7075-7088. ISSN 0892-6638

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The early life gut microbiota plays a crucial role in regulating and maintaining the intestinal barrier, with disturbances in these communities linked to dysregulated renewal and replenishment of intestinal epithelial cells. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period, and which host and microbial factors mediate these responses. Surprisingly, neonatal mice (Day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of liposaccharide (LPS), with Day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses. When we profiled microbiota and metabolites, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia, and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes, and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Antibiotic treatment of neonates restored LPS-induced small intestinal cell shedding, whereas adult fecal microbiota transplant alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlights areas for further investigation.

Item Type: Article
Uncontrolled Keywords: antibiotics,cell shedding,early life,fecal microbiota transplant,inflammation,intestinal epithelium,metabolites,microbiota,biotechnology,biochemistry,molecular biology,genetics ,/dk/atira/pure/subjectarea/asjc/1300/1305
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
Faculty of Science > School of Pharmacy
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health
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Depositing User: LivePure Connector
Date Deposited: 22 Apr 2020 14:41
Last Modified: 19 Oct 2023 02:40
DOI: 10.1096/fj.202000042R


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