Type 1 Diabetes (T1D) results from immune attacks on pancreatic beta cells by T lymphocytes. Our research focuses on the gut microbiota's role in preventing this autoimmunity. We've explored cathelicidin's involvement in T1D and extended our investigation to other antimicrobial peptides (AMPs), specifically mBD14. Our findings show mBD14's expression in pancreatic cells is crucial for preventing T1D in NOD mice, as it stimulates regulatory B cells via TLR2, leading to protective immune responses. Further, mBD14's expression is influenced by gut microbiota metabolites and genetic factors. Our work underscores the importance of gut-microbiota and immune cell interactions in T1D prevention.

Subsequent research revealed the significance of intestinal AMPs in T1D, highlighting how environmental changes affecting gut microbiota contribute to autoimmune diseases. Specifically, we discovered that defective AMP expression in NOD mice and T1D patients leads to intestinal inflammation and dysbiosis, promoting autoimmune responses. Treating pregnant NOD mice with CRAMP-expressing probiotics restored gut homeostasis in their offspring, preventing T1D. This probiotic, which also counters obesity, has been patented with plans for clinical trials, demonstrating the gut microbiota's potential in T1D therapy.

Overall, AMPs appear both as central regulator of the systemic immune system via their ability to regulate the gut microbiota and also as peripheral regulator of the local immune system via their direct immunomodulatory abilities.