Cargando…
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
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 (...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162144/ https://www.ncbi.nlm.nih.gov/pubmed/29875401 http://dx.doi.org/10.1038/s41385-018-0034-3 |
_version_ | 1783359089160486912 |
---|---|
author | Shen, Xi Liu, Liping Peek, Richard M. Acra, Sari A. Moore, Daniel J. Wilson, Keith T. He, Fang Polk, D. Brent Yan, Fang |
author_facet | Shen, Xi Liu, Liping Peek, Richard M. Acra, Sari A. Moore, Daniel J. Wilson, Keith T. He, Fang Polk, D. Brent Yan, Fang |
author_sort | Shen, Xi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6162144 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
record_format | MEDLINE/PubMed |
spelling | pubmed-61621442018-12-06 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, Xi Liu, Liping Peek, Richard M. Acra, Sari A. Moore, Daniel J. Wilson, Keith T. He, Fang Polk, D. Brent Yan, Fang Mucosal Immunol Article 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. 2018-06-06 2018-09 /pmc/articles/PMC6162144/ /pubmed/29875401 http://dx.doi.org/10.1038/s41385-018-0034-3 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Shen, Xi Liu, Liping Peek, Richard M. Acra, Sari A. Moore, Daniel J. Wilson, Keith T. He, Fang Polk, D. Brent Yan, Fang 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162144/ https://www.ncbi.nlm.nih.gov/pubmed/29875401 http://dx.doi.org/10.1038/s41385-018-0034-3 |
work_keys_str_mv | AT shenxi supplementationofp40alactobacillusrhamnosusggderivedproteininearlylifepromotesepidermalgrowthfactorreceptordependentintestinaldevelopmentandlongtermhealthoutcomes AT liuliping supplementationofp40alactobacillusrhamnosusggderivedproteininearlylifepromotesepidermalgrowthfactorreceptordependentintestinaldevelopmentandlongtermhealthoutcomes AT peekrichardm supplementationofp40alactobacillusrhamnosusggderivedproteininearlylifepromotesepidermalgrowthfactorreceptordependentintestinaldevelopmentandlongtermhealthoutcomes AT acrasaria supplementationofp40alactobacillusrhamnosusggderivedproteininearlylifepromotesepidermalgrowthfactorreceptordependentintestinaldevelopmentandlongtermhealthoutcomes AT mooredanielj supplementationofp40alactobacillusrhamnosusggderivedproteininearlylifepromotesepidermalgrowthfactorreceptordependentintestinaldevelopmentandlongtermhealthoutcomes AT wilsonkeitht supplementationofp40alactobacillusrhamnosusggderivedproteininearlylifepromotesepidermalgrowthfactorreceptordependentintestinaldevelopmentandlongtermhealthoutcomes AT hefang supplementationofp40alactobacillusrhamnosusggderivedproteininearlylifepromotesepidermalgrowthfactorreceptordependentintestinaldevelopmentandlongtermhealthoutcomes AT polkdbrent supplementationofp40alactobacillusrhamnosusggderivedproteininearlylifepromotesepidermalgrowthfactorreceptordependentintestinaldevelopmentandlongtermhealthoutcomes AT yanfang supplementationofp40alactobacillusrhamnosusggderivedproteininearlylifepromotesepidermalgrowthfactorreceptordependentintestinaldevelopmentandlongtermhealthoutcomes |