Lactobacilli Modulate Epithelial Cytoprotection through the Nrf2 Pathway.
An optimal gut microbiota influences many beneficial processes in the metazoan host. However, the molecular mechanisms that mediate and function in symbiont-induced host responses have not yet been fully characterized. Here, we report that cellular ROS enzymatically generated in response to contact with lactobacilli in both mice and Drosophila has salutary effects against exogenous insults to the intestinal epithelium via the activation of Nrf2 responsive cytoprotective genes. These data show that the xenobiotic-inducible Nrf2 pathway participates as a signaling conduit between the prokaryotic symbiont and the eukaryotic host. Indeed, our data imply that the capacity of lactobacilli to induce redox signaling in epithelial cells is a highly conserved hormetic adaptation to impel cellular conditioning to exogenous biotic stimuli. These data also highlight the role the microbiota plays in eukaryotic cytoprotective pathways and may have significant implications in the characterization of a eubiotic microbiota.
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Rheinallt M
RM
Jones
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Chirayu
C
Desai
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Trevor M
TM
Darby
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Liping
L
Luo
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Alexandra A
AA
Wolfarth
Department of Immunology and Microbiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Christopher D
CD
Scharer
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Courtney S
CS
Ardita
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
April R
AR
Reedy
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Erin S
ES
Keebaugh
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: aneish@emory.edu.
Andrew S
AS
Neish
D000818:Animals; D004330:Drosophila / Q000378:metabolism* / Q000382:microbiology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology; D048191:Lactiplantibacillus plantarum / Q000378:metabolism* / Q000472:pathogenicity; D052201:Lacticaseibacillus rhamnosus / Q000378:metabolism* / Q000472:pathogenicity; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D015398:Signal Transduction
D051267:NF-E2-Related Factor 2