Lactobacillus suntoryeus inhibits pro-inflammatory cytokine expression and TLR-4-linked NF-κB activation in experimental colitis

Abstract

Lactic acid bacteria (LAB) can improve disturbances of indigenous microflora as well as inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. We examined the anticolitic effect of Lactobacillus suntoryeus HY7801, which inhibited toll-like receptor (TLR)-4-linked NF-kappaB activation in human embryonic kidney (HEK) cells, in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitic mice. We measured the ability of commercial and intestinal LAB to inhibit lipopolysaccharide (LPS)-stimulated, TLR-4-linked NF-kappaB activation in HEK cells, as well as to inhibit colitis outcomes in TNBS-induced colitic mice. We also measured levels of the inflammatory markers, interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6, and their transcription factor, NF-kappaB, in intestinal mucosa by enzyme-linked immunosorbent assay and immunoblotting. LAB inhibited TLR-4-linked NF-kappaB activation, and L. suntoryeus HY7801 was the most potent inhibitor. Intrarectal treatment of TNBS in mice caused colon shortening and also increased colonic expression of IL-1beta, IL-6, and TNF-alpha expression. However, oral administration of Lactobacillus HY7801 (100 mg/kg) inhibited colon shortening (p < 0.001) and myeloperoxidase activity in TNBS-induced colitic mice (p < 0.0002) and also decreased colonic expression of IL - 1beta (p < 0.003), IL-6 (p < 0.0001), and TNF-alpha (p < 0.0001). Lactobacillus HY7801 inhibited the NF-kappaB activation and TLR-4 expression induced by TNBS, as well as the expression of cyclooxygenase 2. Lactobacillus HY7801 also reduced the activity of intestinal bacterial glycosaminoglycan degradation and beta-glucuronidase induced by TNBS. L. suntoryeus HY7801 can improve colitis via the inhibition of TLR-4-linked NF-kappaB activation.