Keith Wilson
Faculty Member
Last active: 8/13/2019

Supplementation of p40, a Lactobacillus rhamnosus GG-derived protein, in early life promotes epidermal growth factor receptor-dependent intestinal development and long-term health outcomes.

Shen X, Liu L, Peek RM, Acra SA, Moore DJ, Wilson KT, He F, Polk DB, Yan F
Mucosal Immunol. 2018 11 (5): 1316-1328

PMID: 29875401 · PMCID: PMC6162144 · DOI:10.1038/s41385-018-0034-3

The beneficial effects of the gut microbiota on growth in early life are well known. However, knowledge about the mechanisms underlying regulating intestinal development by the microbiota is limited. p40, a Lactobacillus rhamnosus GG-derived protein, transactivates epidermal growth factor receptor (EGFR) in intestinal epithelial cells for protecting the intestinal epithelium against injury and inflammation. Here, we developed p40-containing pectin/zein hydrogels for targeted delivery of p40 to the small intestine and the colon. Treatment with p40-containing hydrogels from postnatal day 2 to 21 significantly enhanced bodyweight gain prior to weaning and functional maturation of the intestine, including intestinal epithelial cell proliferation, differentiation, and tight junction formation, and IgA production in early life in wild-type mice. These p40-induced effects were abolished in mice with specific deletion of EGFR in intestinal epithelial cells, suggesting that transactivation of EGFR in intestinal epithelial cells may mediate p40-regulated intestinal development. Furthermore, neonatal p40 treatment reduced the susceptibility to intestinal injury and colitis and promoted protective immune responses, including IgA production and differentiation of regulatory T cells, in adult mice. These findings reveal novel roles of neonatal supplementation of probiotic-derived factors in promoting EGFR-mediated maturation of intestinal functions and innate immunity, which likely promote long-term beneficial outcomes.

MeSH Terms (19)

Animals Bacterial Proteins Cell Differentiation Cell Proliferation Epithelial Cells ErbB Receptors Female Hydrogels Immunity, Innate Immunoglobulin A Intestinal Mucosa Lactobacillus rhamnosus Mice Mice, Inbred C57BL Probiotics T-Lymphocytes, Regulatory Tight Junctions Time Transcriptional Activation

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