Background

Changes in the gut microbiota have been observed in a wide variety of illnesses and conditions. A dysbiotic gut microbiota loses homeostatic balance due to changes in the ratios between commensal and pathogenic bacteria. Dysbiosis can be observed when there are large changes in the makeup of the microbiota, with certain species increasing or decreasing in number (Clemente et al., 2012; Rajilic-Stojanovic, 2013). Moreover changes in gut microbiota composition (which may affect metabolites such as SCFAs) associate with many inflammatory diseases (Clemente et al., 2012), including T1D (de Goffau et al., 2013; Endesfelder et al., 2014). For example, patients with, or people who are predisposed to, autoimmune type 1 diabetes typically show a decrease in Firmicutes abundance and an increase in their Bacteroidetes abundance (Giongo et al., 2011). In contrast, various types of inflammatory bowel diseases (IBD), such as ulcerative colitis or Crohn’s disease show the opposite (Frank et al., 2007; Spor et al., 2011). One possibility for treatment of T1D is the use of beneficial bacteria, following their identification and successful trialing. For example, Lactobacillus johnsonii isolated from diabetes resistant rats was able to prevent T1D development in the spontaneous rat model of T1D (Valladares et al., 2010). Likewise, transfer of microbiota from male mice, who are less prone to develop T1D, to female mice reduced their rates of T1D, which correlated with changes in the mouse’s hormone levels (Markle et al., 2013). We used diets that reshape the gut microbiota composition and induced the release of microbial short chain fatty acids (SCFAs). In this study, we have demonstrated that particularly the SCFA acetate and butyrate reduced the onset of T1D in NOD mice (Marino et al., 2017). We wanted to determine if the protective effect was coming directly from the bacteria, or by the produced microbial SCFA acetate or butyrate. We therefore have developed a protocol to harvest the microbiota from diet-fed NOD mice, and transfer it to GF NOD mice, so that we can examine the effects of the altered microbiota and its metabolites on the pathogenesis of T1D.