Abstract
Background and aimsBacteroides fragilis (BF) are Gram-negative anaerobe symbionts present in the colon. Recent studies have reported the beneficial role of BF in maintaining intestinal homeostasis, stimulating host immunologic development, and preventing infectious colitis caused by pathogenic bacteria. Our previous studies showed that monocolonization of germ-free mice with BF significantly reduced colon inflammations and damage.MethodsIn order to investigate the Toll-like receptor-2 (TLR2), TLR4, and interleukin 10 (IL-10) molecular signaling pathways involved in BF-mediated prevention of dextran sulfate sodium (DSS)-induced colitis. The wild-type (WT), TLR4, TLR2, and IL-10 knockout (-/-) germ-free mice grown were with or without BF colonization for 28 days, and then administered 1% DSS in drinking water for 7 day to induce acute ulcerative colitis.ResultsWe compared phenotypes such as weight loss, disease activity, intestinal histological scores, and immunohistochemistry for inflammatory cells. Unlike WT and TLR4-/- mice, the severity of DSS-colitis did not improve in TLR2-/- animals after BF colonization. The BF enhanced anti-inflammatory cytokines IL-10 expression and inhibited pro-inflammatory-related tumor necrosis factor (TNF-α) and IL-6 mRNA expression in both WT and TLR4-/- mice. In contrast, the failed to up-regulated IL-10 and down-regulated the TNF-α and IL-6 in BF colonization TLR2-/- mice. In addition, we further perform IL-10-/- mice to clarify whether the BF through TLR2 /IL-10 pathway to alleviate DSS-colitis. There were no significant differences in colitis severity and pro-inflammatory related genes expression in the IL-10-/- mice with or without BF colonization.ConclusionsThese results indicate the disease-preventing effects of BF in acute DSS-induced colitis may occur through the TLR2/IL-10 signal pathway.
Highlights
Inflammatory bowel diseases (IBD) are characterized by chronic and repeated inflammatory disorders of the gut including Crohn’s disease (CD) and ulcerative colitis (UC); their etiologies remain unknown [1, 2]
Unlike WT and TLR4-/- mice, the severity of dextran sulfate sodium (DSS)-colitis did not improve in Toll-like receptor-2 (TLR2)-/- animals after Bacteroides fragilis (BF) colonization
The failed to up-regulated interleukin 10 (IL-10) and down-regulated the TNF-α and IL-6 in BF colonization TLR2-/- mice
Summary
Inflammatory bowel diseases (IBD) are characterized by chronic and repeated inflammatory disorders of the gut including Crohn’s disease (CD) and ulcerative colitis (UC); their etiologies remain unknown [1, 2]. The pathogenesis of UC is associated with a complex interplay of genetic, immune system, microbial, and environmental factors [3]. It is generally accepted that IBDs are associated with dysregulation of the mucosal immune system in the native gut microbiota in genetically susceptible individuals. Many studies demonstrated that the gut microbial composition is the strongest environmental factor affecting IBD prognosis [4, 5]. The DSS-induced experimental murine colitis model is well-established and shows consistent results in studies of profound inflammatory changes that occur in the gut during disease progression [7,8,9]. Our previous studies showed that monocolonization of germ-free mice with BF significantly reduced colon inflammations and damage
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