Oral probiotic administration induces interleukin-10 production and prevents spontaneous autoimmune diabetes in the non-obese diabetic mouse

• Published in: Diabetologia Vol. 48; no. 8; pp. 1565 - 1575
• Main Authors: CALCINARO, F, DIONISI, S, DE SIMONE, C, DI MARIO, U, FALORNI, A, BOIRIVANT, M, DOTTA, F, MARINARO, M, CANDELORO, P, BONATO, V, MARZOTTI, S, CORNELI, R. B, FERRETTI, E, GULINO, A, GRASSO, F
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.08.2005; Springer Nature B.V
• Subjects: Adoptive Transfer; Animals; Antigens; Bacteria; Biological and medical sciences; Blood Glucose - metabolism; Cell Separation; Cyclophosphamide - pharmacology; Cytokines; Diabetes; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - pathology; Diabetes Mellitus, Type 1 - prevention & control; Diabetes. Impaired glucose tolerance; Disease prevention; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzyme-Linked Immunosorbent Assay; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Immunoenzyme Techniques; Immunohistochemistry; Insulin - metabolism; Interleukin-10 - biosynthesis; Internal medicine; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Medical sciences; Medicine; Mice; Mice, Inbred NOD; Oral administration; Pancreas - pathology; Pathogenesis; Probiotics; Probiotics - therapeutic use; Protein Synthesis Inhibitors - pharmacology; Spleen - cytology; Spleen - drug effects; Spleen - metabolism; Endocrinopathy; Autoimmunity; Immunopathology; Digestive system; Immunomodulation; NOD mouse; Interleukin; Cytokine; Rodentia; Gut; Oral administration; Autoimmune disease; Lymphoid tissue; Autoimmunity ,Gut-associated lymphoid tissue; IL-10; Vertebrata; Mammalia; Mouse; Type 1 diabetes; Animal; Probiotics ,Type 1 diabetes
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-005-1831-2

Recent observations suggest the involvement of the gastrointestinal tract in the pathogenesis of islet autoimmunity. Thus, the modulation of gut-associated lymphoid tissue may represent a means to affect the natural history of the disease. Oral administration of probiotic bacteria can modulate local and systemic immune responses; consequently, we investigated the effects of oral administration of the probiotic compound VSL#3 on the occurrence of diabetes in non-obese diabetic (NOD) mice. VSL#3 was administered to female NOD mice three times a week starting from 4 weeks of age. A control group received PBS. Whole blood glucose was measured twice a week. IFN-gamma and IL-10 production/expression was evaluated by ELISA in culture supernatants of mononuclear cells isolated from Peyer's patches and the spleen, and by real-time PCR in the pancreas. Insulitis was characterised by immunohistochemistry and histomorphometric studies. Early oral administration of VSL#3 prevented diabetes development in NOD mice. Protected mice showed reduced insulitis and a decreased rate of beta cell destruction. Prevention was associated with an increased production of IL-10 from Peyer's patches and the spleen and with increased IL-10 expression in the pancreas, where IL-10-positive islet-infiltrating mononuclear cells were detected. The protective effect of VSL#3 was transferable to irradiated mice receiving diabetogenic cells and splenocytes from VSL#3-treated mice. Orally administered VSL#3 prevents autoimmune diabetes and induces immunomodulation by a reduction in insulitis severity. Our results provide a sound rationale for future clinical trials of the primary prevention of type 1 diabetes by oral VSL#3 administration.