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. However, in a separate study conducted at University of Alabama at Birmingham (UAB), Wolf et al. (2) described an opposite outcome—low disease incidence in NOD mice that were given AW. Both these studies showed profound differences in the gut microbiota of mice that were on AW and neutral pH water (NW) and after they were switched from AW to NW.
In their comments on the article by Sofi et al. (1), Zhao and Tarbell (3) described that they did not observe acceleration of diabetes development in NOD mice that were given AW. While this observation contradicts our two contrasting reports (1,2), these studies using mice from JAX or JAX origin conducted at four different facilities point toward the profound impact of a complex interplay between environmental factors, including the gut microbiota, diet, and housing conditions (such as type of caging and water systems), on T1D incidence in NOD mice. A common conclusion from our reports (1,2) is that the composition of gut microbiota is influenced by water pH and that these microbiota alterations impact the disease outcome. Zhao and Tarbell (3) point out that differences in the basal microbiota of individual facilities could be the reason for variations in the T1D incidence of mice on AW and NW in these studies, and we strongly agree with this conclusion. In fact, Sofi et al. (1) did show that alteration of baseline flora by transferring microbiota from Taconic Farms C57BL/6 mice can cause significant reduction in T1D incidence in JAX NOD mice on AW.
All three research groups, Wolf et al. (2), Sofi et al. (1), and Zhao and Tarbell (3), describe that JAX mice show higher T1D incidence. At the SPF facilities of UIC (between years 2005 and 2011) and MUSC, JAX mice obtained at <8 weeks of age and continued on AW showed a consistent 90–100% T1D incidence, with very few exceptions, by 30 weeks. Further, JAX mice that were continued on AW and bred in these facilities also showed similar T1D incidence, at least for the first 3 generations. The JAX NOD mice at the MUSC facility that were given AW and bred for a long time (>5 generations) had about 80% diabetes within 30 weeks. This relatively low, but consistent, disease incidence and slow progression of T1D could potentially be due to a drift in the microbiota. The observations by Zhao and Tarbell (3) that only <80% of AW- and NW-recipient and by Wolf et al. (2) that only <55% of AW-recipient first-generation JAX NOD mice in National Institutes of Health and UAB facilities developed Th1-biased T1D by 30 weeks further emphasize the impact of basal microbiota and other environmental factors (including the pH of drinking water) on the disease progression in NOD mice housed at different facilities. It appears that the baseline flora of different facilities can affect the disease outcome differently by causing Th-cell biases. In this regard, we recently reported that AW-recipient (SWRxNZB)F1 (SNF1) mice of the MUSC SPF facility develop Th17-biased lupus at a slower pace compared with NW-recipient mice (4), suggesting that the basal microbiota of MUSC facility favors a Th1 type of response. This report reiterates the impact of basal microbiota of each facility on disease incidence in spontaneous models of autoimmunity.
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Duality of Interest. No potential conflicts of interest relevant to this article were reported.
