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Lactobacillus rhamnosus GG-induced Expression of Leptin in the Intestine Orchestrates Epithelial Cell Proliferation.

ABSTRACT: 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.

SUBMITTER: Darby TM

PROVIDER: S-EPMC7160578 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Lactobacillus rhamnosus GG-induced Expression of Leptin in the Intestine Orchestrates Epithelial Cell Proliferation.

Darby Trevor M TM Naudin Crystal R CR Luo Liping L Jones Rheinallt M RM

Cellular and molecular gastroenterology and hepatology 20191223 4

<h4>Background & aims</h4>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.<h4>Methods</h4>Wild-type and knockout mice wer ...[more]

PMID: 31874255

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Project description:BACKGROUND:Acute gastroenteritis develops in millions of children in the United States every year, and treatment with probiotics is common. However, data to support the use of probiotics in this population are limited. METHODS:We conducted a prospective, randomized, double-blind trial involving children 3 months to 4 years of age with acute gastroenteritis who presented to one of 10 U.S. pediatric emergency departments. Participants received a 5-day course of Lactobacillus rhamnosus GG at a dose of 1×1010 colony-forming units twice daily or matching placebo. Follow-up surveys were conducted daily for 5 days and again 14 days after enrollment and 1 month after enrollment. The primary outcome was moderate-to-severe gastroenteritis, which was defined as an illness episode with a total score on the modified Vesikari scale of 9 or higher (scores range from 0 to 20, with higher scores indicating more severe disease), within 14 days after enrollment. Secondary outcomes included the duration and frequency of diarrhea and vomiting, the duration of day-care absenteeism, and the rate of household transmission (defined as the development of symptoms of gastroenteritis in previously asymptomatic household contacts). RESULTS:Among the 971 participants, 943 (97.1%) completed the trial. The median age was 1.4 years (interquartile range, 0.9 to 2.3), and 513 participants (52.9%) were male. The modified Vesikari scale score for the 14-day period after enrollment was 9 or higher in 55 of 468 participants (11.8%) in the L. rhamnosus GG group and in 60 of 475 participants (12.6%) in the placebo group (relative risk, 0.96; 95% confidence interval, 0.68 to 1.35; P=0.83). There were no significant differences between the L. rhamnosus GG group and the placebo group in the duration of diarrhea (median, 49.7 hours in the L. rhamnosus GG group and 50.9 hours in the placebo group; P=0.26), duration of vomiting (median, 0 hours in both groups; P=0.17), or day-care absenteeism (median, 2 days in both groups; P=0.67) or in the rate of household transmission (10.6% and 14.1% in the two groups, respectively; P=0.16). CONCLUSIONS:Among preschool children with acute gastroenteritis, those who received a 5-day course of L. rhamnosus GG did not have better outcomes than those who received placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01773967 .).

Dataset Information

Lactobacillus rhamnosus GG-induced Expression of Leptin in the Intestine Orchestrates Epithelial Cell Proliferation.

Publications

Lactobacillus rhamnosus GG-induced Expression of Leptin in the Intestine Orchestrates Epithelial Cell Proliferation.

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