Bifidobacterium animalis subsp. lactis TISTR 2591 Improves Glycemic Control and Immune Response in Adults with Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Placebo-Controlled Crossover Clinical Trial

<b>Background/Objectives</b>: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder marked by insulin resistance, hyperglycemia, systemic inflammation, and immune imbalance. This randomized, double-blind, placebo-controlled, crossover trial investigated the effects of <i>Bifidobacterium animalis</i> subsp. <i>lactis</i> TISTR 2591 (BA-2591), a probiotic strain isolated in Thailand, on metabolic, immunologic, and safety parameters. <b>Methods</b>: A total of 44 Thai adults (aged 35-65) with T2DM receiving metformin monotherapy were administered BA-2591 (1 × 10⁹ CFU/g/day) or placebo for 6 weeks, followed by a 4-week washout and crossover. <b>Results</b>: Compared to placebo, BA-2591 significantly attenuated fasting blood glucose elevation (Δ = +1.143 mg/dL vs. +12.570 mg/dL; <i>p</i> < 0.001), minimized the increase in insulin resistance (HOMA-IR: Δ = +0.567 vs. +0.980; <i>p</i> = 0.006), and enhanced β-cell function (HOMA-β: Δ = +6.791% vs. -8.313%; <i>p</i> < 0.001). It also elevated immunoglobulin levels (IgM: +150.300 mg/dL; IgG: +261.500 mg/dL; <i>p</i> < 0.001), reduced LDL-C (<i>p</i> = 0.009), and decreased cathepsin D activity (<i>p</i> = 0.005), with no significant changes in IL-6, adiponectin, MDA, hs-CRP, or body composition. No severe adverse effects were reported. <b>Conclusions</b>: BA-2591 was safe and demonstrated modest, adjunctive benefits for fasting glycemia and immunologic profiles over 6 weeks, without changes in body weight or fat mass. These findings support BA-2591 as a potential adjunct to standard care in early T2DM; larger and longer-duration trials are needed to define its effects on longer-term outcomes.