Monocytes from atrial fibrillation patients upregulate phospholipase C gamma 2, driving disease progression through interactions with the gut microbiome, according to a peer-reviewed study published August 29, 2026, in Nature Communications. Atrial fibrillation is the most common sustained cardiac arrhythmia and confers serious risks of stroke and heart failure. Monocyte activation-associated inflammation is implicated in the disorder.
Researchers examined the biological mechanism using a combined atrial fibrillation male mouse model. In these tests, phospho-PLCγ2-positive monocytes recruited directly into the atria. Once present in heart tissue, the monocytes triggered endothelial-to-mesenchymal transition through the secreted phosphoprotein 1-integrin α9β1 signaling axis. The team demonstrated that monocyte-specific deletion of the PLCG2 gene blocked atrial recruitment of these immune cells and reduced atrial fibrillation in the animals.
Bacterial membrane vesicles derived from gut microbiota initiated the signaling sequence by activating spleen tyrosine kinase, known as Syk, alongside PLCG2 inside monocytes. Depleting the gut microbiome with antibiotics produced measurable effects in mice, cutting phospho-PLCγ2-positive monocyte counts in the atria, suppressing endothelial-to-mesenchymal transition, and attenuating atrial fibrillation inducibility. Administering fecal microbiota transplantation reversed each of those protective effects, showing that monocyte-endocardial crosstalk along the gut-heart axis governs the condition.
Bengbu Medical University and Zhejiang University led the investigation, with Pinfang Kang, Dimin Wang, and Peng Teng contributing equally. The authors declared no competing interests. The work received financial backing through grant 82470415 from the National Natural Science Foundation of China, alongside the Anhui Province Outstanding Youth Project, the Clinical Translation Project of Anhui Province, and the Natural Science Research Project of the Anhui Educational Committee.
