Preventive and therapeutic effects of Lactobacillus paracasei B21060-based synbiotic treatment on gut inflammation and barrier integrity in colitic mice

Abstract

Background: Although gut microbiota perturbation is recognized as a main contributing factor to the pathogenesis of inflammatory bowel disease, synbiotic therapies, as prevention or treatment, have remained overlooked.

Objective: To verify whether Lactobacillus paracasei B21060-based synbiotic therapy could prevent or repair colon damage in a mouse model of colitis, we performed treatments before and after colitis induction.

Methods: The experimental study lasted 19 d. Experimental colitis was induced in BALB/c mice by giving them dextran sodium sulfate (DSS, 2.5%) in drinking water (days 7-12) followed by DSS-free water (days 13-19) (DSS group). L. paracasei B21060 (2.5 × 10(7) bacteria/10 g body weight) was orally administered 7 d before DSS [synbiotic as preventive treatment (P-SYN) group] or 2 d after DSS [synbiotic as therapeutic treatment (T-SYN) group] until day 19. Another group was not treated with DSS or synbiotic and was given tap water (control group), for a total of 4 groups.

Results: Compared with the DSS group, both synbiotic-treated groups had significantly less pronounced weight loss and colon damage. Consistently, mRNA levels of chemokine (C-C motif) ligand 5 in the colon were reduced in both P-SYN and T-SYN mice compared with the DSS group (51%, P < 0.05 and 72%, P < 0.001, respectively). In the P-SYN and T-SYN groups, neutrophil elastase transcription was also reduced (51%, P < 0.01 and 59%, P < 0.001, respectively). Accordingly, oxidative/nitrosative stress was lower in P-SYN and T-SYN mice than in the DSS group. In P-SYN and T-SYN mice, colonic gene expression of tumor necrosis factor (47%, P < 0.01 and 61%, P < 0.001, respectively) and prostaglandin-endoperoxide synthase 2 (45%, P < 0.01 and 35%, P < 0.05, respectively) was lower, whereas interleukin 10 mRNA was doubled compared with the DSS group (both P < 0.5). Remarkably, epithelial barrier integrity (zonulin and occludin) and gut protection (β-defensin and mucin expression) were completely restored in P-SYN and T-SYN mice.

Conclusions: Our data highlight the beneficial effects of this synbiotic formulation in acutely colitic mice, suggesting that it may have therapeutic and possibly preventive efficacy in human colitis.

Keywords: DSS colitis; mucin 1; neutrophil recruitment; oxidative/nitrosative stress; probiotic; tight junction; β-defensin 1.