Dietary emulsifier consumption accelerates type 1 diabetes development in NOD mice

Abstract

The rapidly increasing prevalence of type 1 diabetes (T1D) underscores the role of environmental (i.e. non-genetic) determinants of T1D development. Such factors include industrialized diets as well as the intestinal microbiota with which they interact. One component of industrialized diets that deleteriously impact gut microbiota is dietary emulsifiers, which perturb intestinal microbiota to encroach upon their host promoting chronic low-grade intestinal inflammation and metabolic syndrome. Hence, we investigated whether 2 dietary emulsifiers, carboxymethylcellulose (CMC) and polysorbate-80 (P80), might influence the development of T1D in NOD mice, which spontaneously develop this disorder. We observed that chronic emulsifier exposure accelerated T1D development in NOD mice, which was associated with increased insulin autoantibody levels. Such accelerated T1D development was accompanied by compositional and functional alterations of the intestinal microbiota as well as low-grade intestinal inflammation. Moreover, machine learning found that the severity of emulsifier-induced microbiota disruption had partial power to predict subsequent disease development, suggesting that complex interactions occur between the host, dietary factors, and the intestinal microbiota. Thus, perturbation of host-microbiota homeostasis by dietary emulsifiers may have contributed to the post-mid-20th-century increase in T1D.