Altered gut microbiota and gut-derived inflammation impair glucose regulation and promote metabolic endotoxemia, yet evidence on probiotic effects across combined glycaemic, inflammatory and short-chain fatty acid (SCFA) outcomes remains limited. This study investigated the effects of a 12-week multi-species probiotic on glucose homeostasis, incretin hormones, inflammatory biomarkers and circulating SCFAs in adults with subthreshold depression.In a 12-week double-blind, randomised, placebo-controlled trial, 39 adults with subthreshold depression were allocated to either a probiotic supplement containingLF16,LR06,LP01 and Bifidobacterium longum 04 (n = 19) or placebo (n = 20). Fasting glucose, insulin, HOMA-IR, glucose-dependent insulinotropic peptide (GIP), high-sensitivity-reactive protein (hs-CRP), lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14) and SCFAs were evaluated at three time points: baseline, week 6 and week 12. Between-group and treatment × time effects were analysed using general linear models.Probiotic supplementation significantly reduced fasting glucose at 12 weeks compared with placebo (-1.8 vs. 0.1 mmol/L;= 0.036). In the probiotic group, greater reductions in GIP (= 0.012;= 0.037), LBP (< 0.001), sCD14 (= 0.002;= 0.001) and hs-CRP (= 0.047) were also observed compared with placebo. Plasma SCFA concentrations remained largely unchanged, with no significant treatment × time interactions, except for higher valerate levels at 12 weeks in the probiotic group (= 0.019).Twelve weeks of multi-species probiotic supplementation improved fasting glucose, reduced incretin and inflammatory biomarkers and attenuated metabolic endotoxemia, without alterations in circulating SCFAs. These findings support beneficial modulation of metabolic-immune pathways and highlight the promising role of probiotics to enhance glucose regulation and systemic inflammatory tone in adults with subthreshold depression. Background: Methods: Results: Conclusions: Limosilactobacillus fermentum Lacticaseibacillus rhamnosus Lactiplantibacillus plantarum C p p p p p p p p
