Protective Effect of Bacteroides fragilis on TNF-α- Induced Inflammatory Changes in Human Colon Epithelial Cells and in Inflammatory Bowel Disease Mouse Model

Abstract

Abstract Bacteroides fragilis, one of the potential next-generation probiotics, but its protective mechanism is not yet known. We aimed to characterize the anti-inflammatory effect of B. fragilis and to elucidate its mechanism through in vivo and in vitro experiments. An in vitro model of inflammation by induction of colonic cells with TNF-a, and co-cultured with B. fragilis to detect cell viability, apoptosis and invasive capacity. Furthermore, critical proteins of the TLR/NF-κB pathway and the inflammatory cytokines were measured. For animal trials, C57BL/6J male mice were orally administered B. fragilis or PBS once daily for 21 days. Colitis was induced by drinking 2.5% DSS from days 0 to 7. The mice were weighed daily and rectal bleeding, stool condition and blood in the stool were recorded. We found that B. fragilis treatment alone was harmless and had no effect on cell viability or apoptosis. While predictably TNF-α decreased cell viability and increased apoptosis, B. fragilis attenuated this deterioration. The NF-κB pathway and inflammatory cytokines IL-6, IL-8 and IL-1β activated by TNF-α were also blocked by B. fragilis, which was likely mediated by TLR2. Animal studies showed that B. fragilis ameliorated DSS-induced colitis, as evidenced by weight loss, shortened colon length and enhanced barrier function. The colonic tissue levels of inflammatory cytokines (TNF-α, IL1β, IL6) were decreased and IL-10 was increased as a result of B. fragilisadministration. In conclusion, B. fragilisexhibited anti-inflammatory effects whether in vivo or in vitro, and it may be a potential probiotic agent for improving colitis.