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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Calcinaro
F
F
Department of Internal Medicine, University of Perugia, Italy.
Dionisi
S
S
Marinaro
M
M
Candeloro
P
P
Bonato
V
V
Marzotti
S
S
Corneli
R B
RB
Ferretti
E
E
Gulino
A
A
Grasso
F
F
De Simone
C
C
Di Mario
U
U
Falorni
A
A
Boirivant
M
M
Dotta
F
F
D019264:Adoptive Transfer; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002469:Cell Separation; D003520:Cyclophosphamide / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000473:pathology; D019936:Probiotics / Q000627:therapeutic use*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D011500:Protein Synthesis Inhibitors; D016753:Interleukin-10; D003520:Cyclophosphamide