Decoupling Fermentative Metabolism from Host Glucose Regulation in Probiotic Lactobacilli

In vitro fermentative activity is widely used to screen probiotics; however, its relationship to systemic metabolic effects remains uncertain. This study compared glucose consumption, biomass accumulation, and medium acidification in three probiotic strains, Lacticaseibacillus rhamnosus Vahe, Lactiplantibacillus plantarum ZPZ, and Lactobacillus delbrueckii IAHAHI, under standardized conditions. A composite in vitro metabolic index integrated these parameters, and the resulting profiles were compared with previously reported in vivo blood-glucose responses. Lcb. rhamnosus Vahe and Lpb. plantarum ZPZ showed markedly higher glucose consumption than L. delbrueckii IAHAHI (67.50, 66.60, and 19.40 mmol/L, respectively), together with greater biomass accumulation and stronger acidification. Their composite metabolic index values were 1.00 and 0.93, respectively, compared with 0.00 for L. delbrueckii IAHAHI. In contrast, previously reported in vivo observations showed that L. delbrueckii IAHAHI was associated with a statistically significant reduction in blood glucose compared with untreated controls (6.594 ± 0.20 vs. 7.26 ± 0.19 mM, P < 0.05), whereas the blood glucose level in the Lcb. rhamnosus Vahe prevention group did not differ significantly from that of untreated controls (7.707 ± 0.16 vs. 7.26 ± 0.19 mM, P > 0.05) (Pepoyan et al., 2020). These findings indicate that in vitro fermentative intensity does not necessarily predict systemic glucose regulation in vivo. Glucose consumption, biomass accumulation, and acidification should therefore not be regarded as direct proxies for host-level glucose-lowering efficacy, supporting the need for host-relevant validation in probiotic evaluation.