These results suggest a new role for COX and other enteroviruses (inducing INSR, rather than INS, cross-reactivity) in T1DM etiology; identify Clostridia as the triggers of INS cross-reactivity for the first time; and provide the first evidence suggesting a multifactorial, synergistic mechanism for T1DM etiology. Here, INS is linked to type 1 diabetes mellitus.