title: Redox signaling mediated by the gut microbiota.
abstract: The microbiota that inhabits the mammalian intestine can influence a range of physiological functions, including the modulation of immune responses, enhancement epithelial barrier function, and the stimulation of cell proliferation. While the mechanisms by which commensal prokaryotes stimulate immune signaling networks are well-characterized, less is known about the mechanistic control over homeostatic pathways within tissues. Recent reports by our research group have demonstrated that contact between the gut epithelia and some groups of enteric commensal bacteria prompts the rapid generation of reactive oxygen species (ROS) within host cells. Whereas the bacterial-induced production of ROS in phagocytes in response to ligand binding to Formyl Peptide Receptors (FPRs) and ensuing activation of NADPH oxidase 2 (Nox2) is a well-defined mechanism, ROS generated by other cell types such as intestinal epithelia in response to microbial signals via FPRs and the NADPH oxidase 1 (Nox1) is less appreciated. Importantly, enzymatically generated ROS have been shown to function as second messengers in many signal transduction pathways via the transient oxidative activity on sensor proteins bearing oxidant-sensitive thiol groups. Examples of redox sensitive proteins include tyrosine phosphatases that serve as regulators of MAPK pathways, focal adhesion kinase, as well as components involved NF-kB activation. Here, we review the leading edge discoveries gleaned from investigations that focus on microbial-induced generation of ROS and their functional effects on host physiology. These studies identify the functional molecular elements and mechanistic events that mediate the established effects of the normal microbiota on intestinal physiology.
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Whitehead Biomedical Research Building, 615 Michaels St, Room 105-L, Atlanta, GA 30322, United States.
authors.forename: Rheinallt M
authors.initials: RM
authors.lastname: Jones
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Whitehead Biomedical Research Building, 615 Michaels St, Room 105-L, Atlanta, GA 30322, United States. Electronic address: aneish@emory.edu.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Neish
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology; D019255:NADPH Oxidases / Q000378:metabolism; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013559:Symbiosis
chemical_list: D017382:Reactive Oxygen Species; D019255:NADPH Oxidases
keywords: Formyl peptide receptors; Nox enzymes; Probiotics; Reactive oxygen species