Proceedings of the National Academy of Sciences · 2009 · 363 citations · 27 references
Life SciencesImmunologyMicrobiologyInflammationInnate ImmunityMucosal ImmunologyGastrointestinal ImmunologyGastrointestinal InflammationGut HealthInflammatory Bowel DiseaseInnate Immune ResponseProbioticsEpithelial Barrier RegulationEpithelial Innate Immune SignalingEpithelial-derived CytokinesGut Epithelial Barrier FunctionInflammatory Bowel Disease ImmunopathogenesisInnate Immunity PathwaysIntestinal Epithelial Barrier FunctionMicrobiota-barrier Interactions
Probiotic formulations are widely available and are thought to promote gut health, though their mechanisms are unclear and are generally attributed to anti‑inflammatory effects. The study aims to show that the multi‑strain probiotic VSL#3 prevents intestinal inflammation by locally stimulating epithelial innate immune responses. VSL#3 increases epithelial TNF‑α production, activates NF‑κB, and restores barrier function in vivo and in vitro. The results demonstrate that probiotics enhance gut health by stimulating, rather than suppressing, innate immunity, suggesting that innate immune defects may drive intestinal disorders such as inflammatory bowel disease.
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.
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Medicine, Immunology, Oncology +16