A Compartmental Hypothesis Linking Mycobacterium avium subsp. paratuberculosis, Crohn's Disease, and Type 1 Diabetes

We propose that Mycobacterium avium subspecies paratuberculosis (MAP) can act as a common upstream microbial factor in both Crohn's disease (CD) and type 1 diabetes (T1D), producing one condition or the other depending on which anatomical compartment is predominantly affected, rather than through two unrelated mechanisms. A persistent intestinal MAP-associated process may produce Crohn's disease when local intestinal pathology predominates, and may contribute to T1D when barrier dysfunction, translocation, and systemic innate activation instead converge on pancreatic islets in a susceptible host. We detail the mechanistic bridge from intestinal barrier dysfunction to islet-directed immune activation, distinguish this account from the pre-existing agent-agnostic leaky gut model of T1D, and propose eight falsifiable predictions centered on MAP status, endotoxin exposure signature, and translocation markers. Clinical conversion in either compartment—progression to overt T1D, or a flare in quiescent Crohn's disease—may additionally be timed by a superimposed acute inflammatory event, a second hit, for which vaccine adjuvants of any composition are mechanistically tractable candidates: MAP-associated dysbiosis may itself generate a polymicrobial priming environment capable of contributing to inflammasome completion, though whether this manifests as priming or as tolerance is not established and is treated as an open question, making no single vaccine mechanistically privileged over another. This possibility is secondary to, and separable from, the central account, which remains coherent independent of any specific trigger. Molecular mimicry may amplify the core process where confirmed, but is not required to initiate it. We do not claim CD and T1D are the same disease; in a subset of patients they may be compartmentally distinct outcomes of a shared MAP-associated process.