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Indigenous microbiota influence epithelial homeostasis through the activation of Reactive Oxygen Species
Author(s) -
Jones Rheinallt,
Luo Liping,
Neish Andrew
Publication year - 2010
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.24.1_supplement.117.2
Subject(s) - microbiology and biotechnology , reactive oxygen species , biology , axenic , hindgut , stem cell , homeostasis , gut flora , midgut , bacteria , genetics , immunology , ecology , larva
There is increasing recognition of the roles played by enteric bacteria in the biology of metazoan hosts. For example, the microbiota influences epithelial barrier function, immune modulation and cell proliferation. Recently, multiple lines of investigation have shown that the rapid, physiological generation of reactive oxygen species (ROS) is a cardinal response in all metazoans to bacterial stimuli. Using axenic Drosophila, we demonstrate that ROS is rapidly induced in the fly midgut 30 minutes following conventionalization with commensal bacteria, followed by activation of the CncC/Nrf2 signaling pathway, transcriptional activation of CncC/Nrf‐2 responsive genes, and increase in the ratio of oxidized GSH:GSSH. Functionally, ROS stimulated by microbiota in the gut is known to stimulate stem cell proliferation. Consistently, CncC/Nrf‐2 loss of function mutants exhibit reduced stem cell proliferation when conventionalized with natural Drosophila flora. Furthermore, microbially induced ROS production is elevated anterior to the fly hindgut proliferation zone (HPZ), a region functionally analogous to mammalian intestinal crypts, suggesting that the CncC/Nrf2 xenobiotic response pathway is involved in gene regulatory events necessary for normal gut development and homeostasis.