Probiotics Ameliorate Atrial Fibrillation-Associated Biomarkers and Inflammation in Rats via Modulation of the Gut Microbiota and NLRP3 Inflammasome Pathway

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Background: The gut-heart axis, particularly the role of gut microbiota and the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, is increasingly implicated in the pathogenesis of atrial fibrillation (AF). While probiotics show therapeutic potential, their mechanism in AF remains unclear. Objectives: This study investigates whether probiotics mitigate AF pathology by restoring gut microbiota homeostasis and inhibiting NLRP3 activation. Methods: An AF model was induced in rats via acetylcholine (ACH)/CaCl₂ infusion. Animals were divided into five groups: Sham, AF, AF+Probiotics, AF+MCC950 (NLRP3 inhibitor), and AF+Probiotics+MCC950. We analyzed gut microbiota (16S rRNA sequencing), serum short-chain fatty acids (SCFAs; GC-MS), and the expression of NLRP3 pathway components [NLRP3, caspase-1, interleukin-1β (IL-1β)] and AF biomarkers [pentraxin 3 (PTX3), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), chemerin, galectin-3 (Gal-3)] via immunohistochemistry (IHC), Western blot, and real-time quantitative polymerase chain reaction (RT-qPCR). Results: Atrial fibrillation rats exhibited gut dysbiosis, characterized by reduced diversity (Shannon index significantly decreased vs. Sham, P < 0.01), decreased beneficial bacteria (e.g., Lactobacillus), and lower SCFA levels (acetic, propionic, and butyric acids reduced by 40 - 50%, P < 0.05). Probiotics restored microbial diversity, increased SCFA production (to levels comparable to Sham, P < 0.05), and suppressed NLRP3 inflammasome activation, as evidenced by reduced levels of NLRP3, caspase-1, and IL-1β (protein and mRNA expression decreased by 50 - 70%, P < 0.01). Consequently, the expression of key AF biomarkers was significantly downregulated (PTX3, IL-6, TNF-α, chemerin, Gal-3 reduced by 40 - 60%, P < 0.05). The combined intervention of probiotics and MCC950 yielded the most pronounced effects (all markers further reduced vs. either treatment alone, P < 0.05). Conclusions: Probiotics alleviate AF-related inflammation and biomarker expression, potentially by modulating the gut microbiota and inhibiting the NLRP3 inflammasome pathway. These findings highlight the gut-heart axis as a promising target for AF management.

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