Abstract

Abstract Type 1 diabetes (T1D) is an autoimmune disease which occurs due to the interaction of genetically determined and environmental factors. T1D is characterized by progressive destruction of insulin secreting beta-cells by T cells leading to hyperglycemia. The non-obese diabetic (NOD) mouse spontaneously develops T1D similar to that in humans and thus widely used as a model for understanding the immunological basis and treatment of the disease. Incidence of TID in NOD mice is thought to be influenced by the degree of cleanliness of the mouse colony. Recent studies have shown a role for gut microbiota in promoting as well as preventing the disease. In this study, we show that pH of drinking water can have a profound influence not only on the type of commensal bacteria colonized in the gut, but also on the rate of disease progression. NOD mice that were on acidic pH water developed insulitis and hyperglycemia rapidly compared to those on neutral water. Interestingly, segmented filamentous bacteria (SFB) positive fecal transplant resulted in a profoundly suppressed insulitis and T1D incidence in NOD mice that are on acidic pH water. Microbial community analysis by pyrosequencing shows a significant difference in the type of gut microflora among the mice that were on acidic and neutral pH drinking water and this profile was altered by SFB+ fecal transplant. Our study shows that T1D incidence in NOD mice is influenced by the type of gut flora, but not the degree of cleanness alone.

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