Cross-sectional evaluation of transmural healing in patients with Crohn's disease on maintenance treatment with anti-TNF alpha agents.

BACKGROUND: Transmural healing (TH) of Crohn's disease (CD) is a still unexplored and interesting outcome correlated to concept of deep remission. AIM: To assess the rate of TH in CD patients treated with anti-TNF alpha agents using two cross-sectional procedures: bowel sonography (BS) and magnetic resonance enterography (MRE). METHODS: We performed a 2-year observational longitudinal study, evaluating steroid-free clinical remission (CR), mucosal healing (MH), and TH in CD patients who would complete a 2-year treatment period with anti-TNFs. All patients underwent endoscopy, BS, and MRE before and after 2 years of treatment. RESULTS: Forty out of 80 CD patients were treated with anti-TNFs for 2 years. CR was achieved in 24 patients (60%) while MH in 14 (35%). Using BS, TH was observed in 10 patients (25%), while using MRE, TH was observed in 9 patients (23%) (k=0.90; P<0.01). A good agreement was observed between MH and TH, both using BS (k=0.63; P<0.01) and MRE (k=0.64; P<0.01). A poor agreement was found between CR and TH, with both BS and MRE (k=0.27 and 0.29, respectively; P<0.01); even though all patients with TH had achieved CR. CONCLUSIONS: TH can be achieved in about 25% of CD patients treated with anti-TNFs, as shown by BS and MRE. BS could be used as the first cross-sectional procedure to detect TH.

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

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 (ß-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.