Raffaele Simeoli1, Giuseppina Mattace Raso2, Adriano Lama2, Claudio Pirozzi2, Anna Santoro2, Francesca Di Guida2, Marco Sanges3, Ezra Aksoy4, Antonio Calignano2, Agesilao D'Arienzo3, Rosaria Meli5. 1. Department of Pharmacy and Centre for Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom. 2. Department of Pharmacy and. 3. Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; and. 4. Centre for Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom. 5. Department of Pharmacy and meli@unina.it.
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.
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-SYNmice 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-SYNmice than in the DSS group. In P-SYN and T-SYNmice, 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-SYNmice. 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 humancolitis.
Authors: Gabriela Uribe; Romain Villéger; Philippe Bressollier; Rachel N Dillard; Daniel L Worthley; Timothy C Wang; Don W Powell; Maria C Urdaci; Irina V Pinchuk Journal: Cell Microbiol Date: 2018-07-26 Impact factor: 3.715