Abstract Aims Gut microbiota dysbiosis and intestinal barrier disruption are key features of metabolic disorders associated with high-fat diet (HFD) consumption. While probiotics show promise in modulating these pathways, the role of Lactiplantibacillus plantarum Q180 (LPQ), formerly Lactobacillus plantarum Q180, in restoring gut microbial balance and intestinal barrier integrity remains unclear. In this study, we aimed to investigate whether LPQ supplementation alleviated high-fat diet (HFD)-induced gut dysbiosis, intestinal barrier dysfunction, and systemic endotoxemia in a mouse model. Methods and Results Male C57BL/6 J mice received either a normal control diet or an HFD, with the latter administered with or without LPQ or resmetirom (positive control). Gut microbiota composition was assessed via 16S rRNA gene sequencing, and intestinal barrier function was assessed by fecal and serum endotoxin quantification and colonic expression of tight junction and mucin proteins. LPQ supplementation restored microbial balance, increasing short-chain fatty acid-producing genera (Lactobacillus, Bifidobacterium, Blautia, and Faecalibaculum) and reducing potentially pathogenic taxa. These microbial alterations were accompanied by decreased endotoxin levels, upregulation of epithelial tight junction genes (Zo-1, Ocln, and Claudin-1), and downregulation of mucin genes (Muc2 and Muc4). Positive correlations were noted between specific commensal bacteria and barrier-related gene expression, suggesting a microbiota-linked mechanism supporting epithelial integrity. Conclusion LPQ attenuated HFD-induced gut microbial imbalance and intestinal barrier dysfunction, accompanied by reduced systemic endotoxemia. These findings suggest that LPQ may serve as a microbiota-targeted intervention for gut dysbiosis-related metabolic disturbances. Further studies are warranted to validate its long-term and translational potential in humans.
Cho et al. (Thu,) studied this question.