Effect of Latilactobacillus curvatus HY7601 and Lactiplantibacillus plantarum KY1032 on Serum Triglyceride Levels and the Gut–Metabolic Axis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Background/Objectives: Hypertriglyceridemia is a critical cardiovascular risk factor, and the probiotic combination of Latilactobacillus curvatus HY7601 and Lactiplantibacillus plantarum KY1032 (HY+KY) has emerged as a potential therapeutic strategy, though clinical validation in adults with mild hypertriglyceridemia (HTG) is needed. Methods: In this randomized, double-blind, placebo-controlled, 12-week trial, a total of 100 overweight participants with mild HTG were randomized (n = 50 per group). Ultimately, 80 participants completed the study without major protocol violations and were evaluated in the Per-Protocol Set (probiotics group: n = 41; placebo group: n = 39). Primary outcomes included changes in serum lipid profiles such as triglycerides (TG) and LDL cholesterol (LDL), metabolic biomarkers, and gut microbiota composition analyzed via 16S rRNA gene sequencing. Results: HY+KY supplementation led to significant reductions in serum TG (158.61 ± 23.17 to 139.54 ± 54.31 mg/dL, p = 0.009) and LDL (129.22 ± 28.45 to 111.34 ± 21.03 mg/dL, p = 0.005) compared to baseline, while the placebo group showed no significant changes. Furthermore, the HY+KY group exhibited a significant increase in Apolipoprotein CII (ApoC2, p = 0.034) and a reduction in fasting glucose levels (p = 0.021). Microbiome analysis revealed that HY+KY significantly increased alpha diversity (Shannon index, p = 0.012) and significantly altered the microbial community structure (beta diversity, p = 0.015). Co-occurrence network analysis identified Lactiplantibacillus as a highly connected central node that is strongly associated with the favorable shifts in clinical biomarkers. Conclusions: HY+KY supplementation was associated with improved fasting TG and LDL profiles in adults with mild HTG, alongside coordinated changes in ApoC2, fasting glucose, and gut microbiota structure. These findings support the potential of probiotic supplementation as a preventive nutritional approach in borderline HTG.