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Lactobacillus rhamnosus GG‐mediated expression of leptin in the intestine induces cell proliferation
Author(s) -
Darby Trevor M,
Luo Liping,
Naudin Crystal,
Jones Rheinallt M
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.38.6
Subject(s) - lactobacillus rhamnosus , microbiology and biotechnology , intestinal epithelium , biology , signal transduction , paneth cell , leptin , nox1 , gut flora , cell growth , epithelium , nadph oxidase , immunology , small intestine , endocrinology , lactobacillus , biochemistry , reactive oxygen species , obesity , genetics , fermentation
Identifying the functional elements that mediate efficient gut epithelial development and homeostasis is essential for understanding intestinal health and disease. Some of the molecular events that function in optimal gut epithelial health are induced after the colonization of the intestine by symbiotic bacteria. Some lactobacilli, when in contact with the gut epithelium, induce the activation of signaling pathways that function in cell proliferation, cell migration, epithelial wound sealing and cytoprotection. These processes involve the generation of non‐toxic physiological levels of ROS by NADPH oxidase (Nox1) and ensuing activation of the Nrf2 pathway signaling. However, the downstream functional elements that respond to Nox1‐generated ROS and mediate these events are yet to be fully described. Here, we show that ingestion of Lactobacillus rhamnosus GG induces elevated levels of Leptin in the gut epithelia, which as well as functioning in the context of metabolism, also has pleiotropic activity as a chemokine that induces cell proliferation. Using gut epithelial specific knockout mice, we show that L. rhamnosus GG –induced elevated levels of Leptin is dependent on a functional Nox1 in the colonic epithelium, and that L. rhamnosus GG –induced cell proliferation is dependent, on both Nox1 and on Leptin. We also show that L. rhamnosus GG induces JAK‐STAT signaling pathway in the gut in a Nox1 and Leptin dependent manner. Our data suggest that L. rhamnosus GG elevates Leptin levels in the gut epithelium, and that Leptin then acts as a chemokine promoting cell proliferation through the upregulation of JAK‐STAT pathway signaling. These results demonstrate a novel role for Leptin in the response to colonization by lactobacilli, where Leptin is involved in the transduction of signals from symbiotic bacteria to sub epithelial compartments, where it modulates intestinal development and homeostasis. Support or Funding Information NIH Grants R01DK098391 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .