pH of Drinking Water Influences the Composition of Gut Microbiome and Type 1 Diabetes Incidence

Abstract

Nonobese diabetic (NOD) mice spontaneously develop type 1 diabetes (T1D), progression of which is similar to that in humans, and therefore are widely used as a model for understanding the immunological basis of this disease. The incidence of T1D in NOD mice is influenced by the degree of cleanliness of the mouse colony and the gut microflora. In this report, we show that the T1D incidence and rate of disease progression are profoundly influenced by the pH of drinking water, which also affects the composition and diversity of commensal bacteria in the gut. Female NOD mice that were maintained on acidic pH water (AW) developed insulitis and hyperglycemia rapidly compared with those on neutral pH water (NW). Interestingly, forced dysbiosis by segmented filamentous bacteria (SFB)-positive fecal transfer significantly suppressed the insulitis and T1D incidence in mice that were on AW but not in those on NW. The 16S rDNA–targeted pyrosequencing revealed a significant change in the composition and diversity of gut flora when the pH of drinking water was altered. Importantly, autoantigen-specific T-cell frequencies in the periphery and proinflammatory cytokine response in the intestinal mucosa are significantly higher in AW-recipient mice compared with their NW counterparts. These observations suggest that pH of drinking water affects the composition of gut microflora, leading to an altered autoimmune response and T1D incidence in NOD mice.

Role of SFB in autoimmune arthritis

“…We did not perform monocolonization experiments in our system, and thus it is entirely possible that SFB acts here indirectly, as observed in models of colitis 13 or type 1 diabetes. 37 The most interesting result from this study, however, is the unique regulation of a T-cell intrinsic tolerance mechanism achieved by SFB-derived inflammatory signals. Recent observations suggest that commensal bacteria can also enhance anti-tumor T cell responses following chemotherapy.…”

Reciprocity in Microbiome and Immune System Interactions and its Implications in Disease and Health

“…In NOD mice, gluten free diet changes microbial communities in the gut and lowers the incidence of diabetes [117]. NOD mice that receive acidified rather than neutral drinking water show an altered compostion of gut microbiota that is associated with more suceptiblity to the development of insulitis and hyperglycemia [118]. Diet in the long run has an influence on the balance of major bacterial phyla by changing the ratio of Bacteroides to Firmicutes in the gut [108].…”

“…Fecal microbiota transplantation has shown to be promising in the treatment of Clostridium difficile infections [127]. Fecal transfer from SFB positive donors suppresses type 1 diabetes in recipient NOD mice [118].…”

Response to Comment on Sofi et al. pH of Drinking Water Influences the Composition of Gut Microbiome and Type 1 Diabetes Incidence. Diabetes 2014;63:632–644

“…We recently described that drinking water pH influences the composition of gut microbiota and type 1 diabetes (T1D) incidence in nonobese diabetic (NOD) mice (1,2). In a study conducted at the specific pathogen-free (SPF) facilities of University of Illinois at Chicago (UIC) and Medical University of South Carolina (MUSC), Sofi et al (1) reported an association between consumption of acidic drinking water (AW) and high diabetes incidence in NOD mice obtained from The Jackson Laboratory (JAX) and mice from the breeding colonies of UIC and MUSC.…”