title: Probiotics promote gut health through stimulation of epithelial innate immunity.
abstract: Probiotic formulations are widely available and have a variety of proposed beneficial effects, including promotion of gut health. The mechanisms of action of probiotic bacteria in the intestine are still unclear but are generally attributed to an antiinflammatory effect. Here, we demonstrate that the multiple probiotic formulation VSL#3 prevents the onset of intestinal inflammation by local stimulation of epithelial innate immune responses (i.e., increased production of epithelial-derived TNF-alpha and restoration of epithelial barrier function in vivo). We also demonstrate that probiotic bacteria stimulate epithelial production of TNF-alpha and activate NF-kappaB in vitro. Our results support the hypothesis that probiotics promote gut health through stimulation, rather than suppression, of the innate immune system. Furthermore, our findings provide the perspective that defects in innate immunity may play a critical role in the pathogenesis and progression of intestinal disorders, such as inflammatory bowel disease.
authors.affiliation: Digestive Health Research Center, University of Virginia Health System, Charlottesville, VA 22908, USA.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Pagnini
authors.forename: Rubina
authors.initials: R
authors.lastname: Saeed
authors.forename: Giorgos
authors.initials: G
authors.lastname: Bamias
authors.forename: Kristen O
authors.initials: KO
authors.lastname: Arseneau
authors.forename: Theresa T
authors.initials: TT
authors.lastname: Pizarro
authors.forename: Fabio
authors.initials: F
authors.lastname: Cominelli
mesh_terms: D000818:Animals; D017077:Culture Media, Conditioned / Q000737:chemistry; D004269:DNA, Bacterial / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D007079:Ileitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D007113:Immunity, Innate; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D019936:Probiotics / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D017077:Culture Media, Conditioned; D004269:DNA, Bacterial; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha