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 (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.
Department of Pharmacy and Centre for Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.
Raffaele
R
Simeoli
Department of Pharmacy and.
Giuseppina
G
Mattace Raso
Department of Pharmacy and.
Adriano
A
Lama
Department of Pharmacy and.
Claudio
C
Pirozzi
Department of Pharmacy and.
Anna
A
Santoro
Department of Pharmacy and.
Francesca
F
Di Guida
Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; and.
Marco
M
Sanges
Centre for Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.
Ezra
E
Aksoy
Department of Pharmacy and.
Antonio
A
Calignano
Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; and.
Agesilao
A
D'Arienzo
Department of Pharmacy and meli@unina.it.
Rosaria
R
Meli
D000818:Animals; D003092:Colitis / Q000517:prevention & control / Q000628:therapy*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000382:microbiology*; D007249:Inflammation / Q000517:prevention & control / Q000628:therapy; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007778:Lactobacillus; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D058616:Synbiotics; D015854:Up-Regulation; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism
C120555:Defb1 protein, mouse; D018396:Mucin-1; D047495:PPAR gamma; D012333:RNA, Messenger; D023083:beta-Defensins; C577056:muc1 protein, mouse; D016753:Interleukin-10; D008315:Malondialdehyde; D016264:Dextran Sulfate; D009195:Peroxidase; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
DSS colitis; mucin 1; neutrophil recruitment; oxidative/nitrosative stress; probiotic; tight junction; β-defensin 1