Probiotics in type 1 diabetes: immunomodulatory mechanisms and the unresolved question of clinical efficacy

Type 1 Diabetes (T1D) is a common autoimmune disease worldwide, which is associated with imbalanced gut microbiota. Intestinal dysbiosis plays a key role in the pathogenesis of T1D, and it may affect immune tolerance and autoimmune responses of pancreatic islet β-cells. As a potential immunomodulator, probiotics can help restore this balance, regulate immune responses, and reduce the risk of T1D. Although probiotics offer a logical immunomodulatory strategy to restore microbial and immune homeostasis, the translational gap between robust preclinical mechanisms and inconsistent clinical outcomes remains poorly defined. This review summarizes the mechanisms of action and clinical research progress of probiotics in the immunotherapy of T1D. Firstly, it elaborates on the key pathways through which probiotics regulate the gut-immune-pancreas axis. Subsequently, it conducts a comparative analysis of important clinical trials on probiotic therapy for T1D in recent years, comparing the differences in efficacy of different intervention timings, different bacterial strains, etc., in the prevention and adjuvant treatment of T1D, and explores their relationships with patients' age, disease duration, and genetic background. Meanwhile, it points out the limitations of current research, so as to provide important references for future studies. Furthermore, this review looks forward to the future directions of probiotics in the field of T1D immunotherapy, including innovative approaches such as engineered bacteria transformation, targeted delivery, and personalized microbiota intervention. Finally, it evaluates the safety of probiotics in the treatment of T1D, aiming to explore an individualized probiotic therapy method and lay a more reliable foundation for subsequent clinical translation.