Optimizing botanical-prebiotic combinations for type 2 diabetes: The interplay between 2’-fucosyllactose and <i>Gongronema latifolium</i> in glucose regulation.

Combination therapy is a promising approach for multifactorial conditions such as type 2 diabetes, where single agents may be insufficient. Prebiotics like human milk oligosaccharide 2’-fucosyllactose (2-FL) and ethnobotanical agents such as Gongronema latifolium have demonstrated antidiabetic effects individually, but optimal dose ratios for combination therapy remain unexplored. This study aimed to evaluate the dose-dependent interactions between 2-FL and G. latifolium in a streptozotocin-nicotinamide (STZ-NAD, 70:50 mg/kg) mouse model of type 2 diabetes. 2-FL produced a delayed glucose-lowering effect, while G. latifolium acted rapidly. Blood glucose was largely unaffected in normoglycemic mice, except at high-dose G. latifolium (400 mg/kg), which progressively reduced glucose from day 21. Both agents significantly reduced postprandial glucose area under the curve (AUC) in diabetic and normoglycemic mice. The 25% effective doses were 1.89 g/kg for 2-FL and 88.68 mg/kg for G. latifolium. A combination of 0.95 g/kg 2-FL and 44.34 mg/kg G. latifolium produced an additive effect (CI = 1), whereas 0.6 g/kg 2-FL with 24 mg/kg G. latifolium was synergistic (CI < 1). These findings demonstrate that the therapeutic interaction between 2-FL and G. latifolium is non-linear and dose-ratio dependent. This underscores the importance of rational dose-ratio optimization when designing botanical-prebiotic combination therapies for metabolic disorders.