Type 1 Diabetes: an Association Between Autoimmunity, the Dynamics of Gut Amyloid-producing E. coli and Their Phages

The etiopathogenesis of type 1 diabetes (T1D), a common autoimmune disorder, is not completely understood. Recent studies suggested the gut microbiome plays a role in T1D. We have used public longitudinal microbiome data from T1D patients to analyze amyloid-producing bacterial composition and found a significant association between initially high amyloid-producing Escherichia coli abundance, subsequent E. coli depletion prior to seroconversion, and T1D development. In children who presented seroconversion or developed T1D, we observed an increase in the E. coli phage/E. coli ratio prior to E. coli depletion, suggesting that the decrease in E. coli was due to prophage activation. Evaluation of the role of phages in amyloid release from E. coli biofilms in vitro suggested an indirect role of the bacterial phages in the modulation of host immunity. This study for the first time suggests that amyloid-producing E. coli, their phages, and bacteria-derived amyloid might be involved in pro-diabetic pathway activation in children at risk for T1D.