MICROBIOTA AND IMMUNE MICROENVIRONMENT IN POUCHITIS (MEP1): INTERIM ANALYSIS OF A RANDOMIZED CONTROLLED TRIAL ON ORAL ADMINISTRATION OF LACTOBACILLUS CASEI DG FOR8 WEEKS AFTER ILEOSTOMY CLOSURE
Imerio Angriman1, Melania Scarpa*2, Renata D'Inca3, Matteo Martinato3, Andromachi Kotsafti2, Antonino Caruso3, Edoardo V. Savarino3, Romeo Bardini1, Ignazio Castagliuolo4, Marco Scarpa1
1General Surgery Unit, University Hospital of Padova, Padova, Italy; 2Laboratory of Advanced Traslational research, Veneto Institute of Oncology, Padova, 35128, Italy; 3Gastroenterology Unit, University Hospital of Padova, Padova, Italy; 4University of Padova, Padova, Italy
BACKGROUND: An imbalance in gut microbiota seems to contribute to the development of ulcerative colitis (UC) and, after restorative proctocolectomy, of chronic pouchitis. Although it has been suggested that probiotic supplementation is an effective approach to colitis, its effects on intestinal flora and on activation of dendritic cells, macrophage and T cells in the ileal pouch mucosa have never been explored.
AIM: To evaluate the effect of Lactobacillus casei (L. casei) DG, a probiotic strain, on activation of dendritic cells, macrophage and T cells in the ileal pouch mucosa.
METHODS: Eighteen patients who had restorative proctocolectomy were randomized to receive a daily oral supplementation of L. casei DG or placebo for 8 weeks from the ileostomy closure to a pouch endoscopy after 8 weeks (12 L. casei DG and 6 placebo). Biopsies were collected from the pouch mucosa to assess activation of dendritic cells, macrophage (Cd40 and Cd80 expression) and T cells (CD69 expression) by dual staining flow cytofluorimentry. Wilcoxon match paired rank test and Mann-Whitney U test were used.
RESULTS: No patients showed any sign of clinical pouchitis at ileostomy closure. After 8 weeks from the ileostomy closure, in the placebo group, the activated macrophages (CD163+CD40+, p=0.05), dendritic cells (CD1a+CD40+, p=0.02 and CD1a+CD80+, p=0.02) and T lymphocytes (Cd4+cd69+,p=0.04 and CD8+CD69+, p=0.02) were significantly higher than baseline. On the contrary, after 8 weeks from the ileostomy closure, in the L. casei DG group, only dendritic cells (CD1a+CD80+, p=0.05) were significantly higher than baseline while T lymphocytes (CD8+CD69+, p=0.09) tended to be lower than baseline. After 8 weeks from the ileostomy closure, CD8+CD69+ MFI was significant higher (p=0.03) in the L. casei DG group than in the placebo group but the CD8+Cd69+ cell rate tended to be lower in the L. casei DG group(p=0.09).
CONCLUSIONS: Manipulation of mucosal microbiota by L. casei DG prevented the activation of mucosal T cells and innate immune system. These preliminary results encourage completion of this randomized controlled trial aimed to decrease the risk of chronic pouchitis.
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