Bifidobacterium longum and VSL#3® amelioration of TNBS-induced colitis associated with reduced HMGB1 and epithelial barrier impairment

Abstract

Probiotics are a beneficial treatment for inflammatory bowel disease (IBD). However, studies comparing the effects of similar doses of single and mixed probiotics on IBD are scarce. High mobility group box 1 (HMGB1) is an important proinflammatory mediator involved IBD development. The present study assessed fecal HMGB1 levels in IBD patients and compared the effects of similar doses of Bifidobacterium longum (Bif) versus VSL#3® on HMGB1 levels in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced murine colitis. Twenty-four mice were divided into four treatment groups (n = 6 per group): ethanol (control), TNBS, TNBS + Bif, and TNBS + VSL#3®. Bif and VSL#3® (4 × 109 CFU/dose) were administered daily by intragastric gavage, beginning 3 d before TNBS treatment, for a total of 7 d. Fecal HMGB1 levels were higher in both active IBD patients and TNBS-induced colitis mice versus their respective controls. Both Bif and VSL#3® improved intestinal inflammation and fecal microbiota imbalance in TNBS-induced colitis mice. Both treatments also reduced serum and fecal HMGB1 levels as well as increased expression of zonula occludins-1, occludin, and claudin-1 in colon tissues. In Caco-2 cells, HMGB1 reduced transepithelial electrical resistance, zonula occludins-1 protein expression, and increased paracellular permeability of FITC-dextran; the opposite was found with both probiotic treatments. These findings suggest Bif and VSL#3® have similar beneficial effects on TNBS-induced colitis, possibly through inhibition of HMGB1 release and subsequent HMGB1-mediated gut barrier dysfunction. The present study provides novel insights into probiotic treatment of IBD.