Lactobacillus rhamnosus GG–induced Expression of Leptin in the Intestine Orchestrates Epithelial Cell ProliferationSummary
Background & Aims: Identifying the functional elements that mediate efficient gut epithelial growth and homeostasis is essential for understanding intestinal health and disease. Many of these processes involve the Lactobacillus-induced generation of reactive oxygen species by NADPH oxidase (Nox1...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-01-01
|
| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X19301808 |
| _version_ | 1818270224921657344 |
|---|---|
| author | Trevor M. Darby Crystal R. Naudin Liping Luo Rheinallt M. Jones |
| author_facet | Trevor M. Darby Crystal R. Naudin Liping Luo Rheinallt M. Jones |
| author_sort | Trevor M. Darby |
| collection | DOAJ |
| description | Background & Aims: Identifying the functional elements that mediate efficient gut epithelial growth and homeostasis is essential for understanding intestinal health and disease. Many of these processes involve the Lactobacillus-induced generation of reactive oxygen species by NADPH oxidase (Nox1). However, the downstream signaling pathways that respond to Nox1-generated reactive oxygen species and mediate these events have not been described. Methods: Wild-type and knockout mice were fed Lactobacillus rhamnosus GG and the transcriptional and cell signaling pathway responses in the colon measured. Corroboration of data generated in mice was done using in organoid tissue culture and in vivo gut injury models. Results: Ingestion of L rhamnosus GG induces elevated levels of leptin in the gut epithelia, which as well as functioning in the context of metabolism, has pleiotropic activity as a chemokine that triggers cell proliferation. Consistently, using gut epithelial-specific knockout mice, we show that L rhamnosus GG–induced elevated levels of leptin is dependent on a functional Nox1 protein in the colonic epithelium, and that L rhamnosus GG–induced cell proliferation is dependent on Nox1, leptin, and leptin receptor. We also show that L rhamnosus GG induces the JAK-STAT signaling pathway in the gut in a Nox1, leptin, and leptin receptor–dependent manner. Conclusions: These results demonstrate a novel role for leptin in the response to colonization by lactobacilli, where leptin functions in the transduction of signals from symbiotic bacteria to subepithelial compartments, where it modulates intestinal growth and homeostasis. |
| first_indexed | 2024-12-12T21:06:53Z |
| format | Article |
| id | doaj.art-e87ae3f2232940a78956e4ffa4db69cd |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-12-12T21:06:53Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-e87ae3f2232940a78956e4ffa4db69cd2022-12-22T00:12:00ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2020-01-0194627639Lactobacillus rhamnosus GG–induced Expression of Leptin in the Intestine Orchestrates Epithelial Cell ProliferationSummaryTrevor M. Darby0Crystal R. Naudin1Liping Luo2Rheinallt M. Jones3Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University School of Medicine, Atlanta, GeorgiaDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University School of Medicine, Atlanta, GeorgiaDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University School of Medicine, Atlanta, GeorgiaDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; Emory Microbiome Research Center, Emory University School of Medicine, Atlanta, Georgia; Correspondence Address correspondence to: Rheinallt M. Jones, PhD, Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University School of Medicine, 615 Michael Street, Atlanta, Georgia 30322. fax: (404) 727-8538.Background & Aims: Identifying the functional elements that mediate efficient gut epithelial growth and homeostasis is essential for understanding intestinal health and disease. Many of these processes involve the Lactobacillus-induced generation of reactive oxygen species by NADPH oxidase (Nox1). However, the downstream signaling pathways that respond to Nox1-generated reactive oxygen species and mediate these events have not been described. Methods: Wild-type and knockout mice were fed Lactobacillus rhamnosus GG and the transcriptional and cell signaling pathway responses in the colon measured. Corroboration of data generated in mice was done using in organoid tissue culture and in vivo gut injury models. Results: Ingestion of L rhamnosus GG induces elevated levels of leptin in the gut epithelia, which as well as functioning in the context of metabolism, has pleiotropic activity as a chemokine that triggers cell proliferation. Consistently, using gut epithelial-specific knockout mice, we show that L rhamnosus GG–induced elevated levels of leptin is dependent on a functional Nox1 protein in the colonic epithelium, and that L rhamnosus GG–induced cell proliferation is dependent on Nox1, leptin, and leptin receptor. We also show that L rhamnosus GG induces the JAK-STAT signaling pathway in the gut in a Nox1, leptin, and leptin receptor–dependent manner. Conclusions: These results demonstrate a novel role for leptin in the response to colonization by lactobacilli, where leptin functions in the transduction of signals from symbiotic bacteria to subepithelial compartments, where it modulates intestinal growth and homeostasis.http://www.sciencedirect.com/science/article/pii/S2352345X19301808LeptinNox1ProbioticLactobacillusProbiotics |
| spellingShingle | Trevor M. Darby Crystal R. Naudin Liping Luo Rheinallt M. Jones Lactobacillus rhamnosus GG–induced Expression of Leptin in the Intestine Orchestrates Epithelial Cell ProliferationSummary Cellular and Molecular Gastroenterology and Hepatology Leptin Nox1 Probiotic Lactobacillus Probiotics |
| title | Lactobacillus rhamnosus GG–induced Expression of Leptin in the Intestine Orchestrates Epithelial Cell ProliferationSummary |
| title_full | Lactobacillus rhamnosus GG–induced Expression of Leptin in the Intestine Orchestrates Epithelial Cell ProliferationSummary |
| title_fullStr | Lactobacillus rhamnosus GG–induced Expression of Leptin in the Intestine Orchestrates Epithelial Cell ProliferationSummary |
| title_full_unstemmed | Lactobacillus rhamnosus GG–induced Expression of Leptin in the Intestine Orchestrates Epithelial Cell ProliferationSummary |
| title_short | Lactobacillus rhamnosus GG–induced Expression of Leptin in the Intestine Orchestrates Epithelial Cell ProliferationSummary |
| title_sort | lactobacillus rhamnosus gg induced expression of leptin in the intestine orchestrates epithelial cell proliferationsummary |
| topic | Leptin Nox1 Probiotic Lactobacillus Probiotics |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X19301808 |
| work_keys_str_mv | AT trevormdarby lactobacillusrhamnosusgginducedexpressionofleptinintheintestineorchestratesepithelialcellproliferationsummary AT crystalrnaudin lactobacillusrhamnosusgginducedexpressionofleptinintheintestineorchestratesepithelialcellproliferationsummary AT lipingluo lactobacillusrhamnosusgginducedexpressionofleptinintheintestineorchestratesepithelialcellproliferationsummary AT rheinalltmjones lactobacillusrhamnosusgginducedexpressionofleptinintheintestineorchestratesepithelialcellproliferationsummary |