<i>Lactobacillus</i> shapes LPS-reservoir modules within the gut microbiota to mitigate atrial fibrillation

ABSTRACT Atrial fibrillation (AF) is the most prevalent clinical arrhythmia, associated with numerous complications, elevated morbidity and mortality rates, and limited therapeutic interventions, which have been confirmed to be related to the intestinal microbiota. However, there is currently limited research on the interaction between gut microbiota and AF. Herein, we integrated the largest Chinese gut microbiota cohort ( n = 355) related to AF to date and identified a marked microbial imbalance in AF patients, characterized primarily by a significant reduction in Lactobacillus abundance. Using a rat model, we validated the role of Lactobacillus in lowering intestinal lipopolysaccharide (LPS) levels and alleviating host inflammation and AF-related symptoms. Mechanistically, microbial network analysis revealed that Lactobacillus promotes the formation of “LPS-reservoir modules,” enhancing microbial community stability and reducing free LPS levels, thereby mitigating AF pathogenesis. These findings offer novel insights into the complex interplay among gut microbiota, LPS, and cardiovascular diseases. IMPORTANCE AF is a common heart rhythm disorder with limited treatment options. While emerging evidence links AF to the gut microbiome, the exact mechanisms remain poorly understood. Here, we analyzed a large cohort of AF patients and discovered a significant depletion of Lactobacillus in their gut microbiota. Using an animal model, we demonstrated that replenishing Lactobacillus reduces systemic inflammation and alleviates AF symptoms. Mechanistically, Lactobacillus promotes the formation of stable microbial networks. This enhanced stability prevents massive bacterial death and turnover, thereby reducing the release of free LPS into the environment. This work is highly significant as it decodes a vital link between gut stability and cardiovascular health, suggesting that Lactobacillus -based probiotics could serve as an innovative strategy for managing AF.