Int J Biol Sci 2022; 18(10):4219-4232. doi:10.7150/ijbs.70644 This issue Cite

Research Paper

Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling

Kun Zuo#, Chen Fang#, Zheng Liu, Yuan Fu, Ye Liu, Lifeng Liu, Yuxing Wang, Xiandong Yin, Xiaoqing Liu, Jing Li, Jiuchang Zhong, Mulei Chen, Li Xu, Xinchun Yang

Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
#Equal contributors.

Citation:
Zuo K, Fang C, Liu Z, Fu Y, Liu Y, Liu L, Wang Y, Yin X, Liu X, Li J, Zhong J, Chen M, Xu L, Yang X. Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling. Int J Biol Sci 2022; 18(10):4219-4232. doi:10.7150/ijbs.70644. https://www.ijbs.com/v18p4219.htm
Other styles

File import instruction

Abstract

Graphic abstract

Rationale: Dysbiotic gut microbiota (GM) and NLRP3 inflammasome are proarrhythmic factors in atrial fibrillation (AF). Herein, whether short-chain fatty acid (SCFA) produced from GM fermentation of dietary fiber serving as invisible mediators is yet unclear. Thus, the current study aimed to determine whether SCFA alleviated from NLRP3 signaling-mediated atrial remodeling protects AF development.

Methods: First, a cross-sectional study based on the GC-MS metabolomics was performed to explore the association between fecal SCFA levels and AF traits in a cohort consisted of 48 individuals. Then, a well-established mice model fed diet deficient or enriched in dietary fiber was established to elucidate the pathophysiological role of SCFA involved in AF susceptibility, atrial remodeling, and G-protein-coupled receptor 43 (GPR43)/NLRP3 signaling. Finally, the effects of SCFA were verified on HL-1 cells.

Results: Fecal SCFA levels were remarkably reduced in AF patients with a declining trend from paroxysmal to persistent AF. Prolonged P wave duration based on surface ECG and increased left atrial diameter gained from echocardiography was identified in low-fiber diet mice but lost in SCFA-supplemented group. Lack of dietary fiber enhanced susceptibility to AF under burst pacing, whereas SCFA might exert a protective effect. The supplementation of SCFA prevented dietary fiber deficiency-upregulated phosphorylation of calmodulin-dependent protein kinase II and ryanodine receptor 2, the disarray fibrosis, collagen expression, and NLRP3 inflammasome activation in atrial tissue. Finally, the AF protective roles of SCFA were identified through GPR43 mediated deactivation of NLRP3 by GPR43 knockdown in HL-1 cells.

Conclusions: SCFA derived from dietary fiber fermentation by gut commensals alleviates AF development via GPR43/NLRP3 signaling.

Keywords: Atrial fibrillation, Short-chain fatty acid, NLRP3 inflammasome, Gut microbiota, Atrial remodeling


Citation styles

APA
Zuo, K., Fang, C., Liu, Z., Fu, Y., Liu, Y., Liu, L., Wang, Y., Yin, X., Liu, X., Li, J., Zhong, J., Chen, M., Xu, L., Yang, X. (2022). Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling. International Journal of Biological Sciences, 18(10), 4219-4232. https://doi.org/10.7150/ijbs.70644.

ACS
Zuo, K.; Fang, C.; Liu, Z.; Fu, Y.; Liu, Y.; Liu, L.; Wang, Y.; Yin, X.; Liu, X.; Li, J.; Zhong, J.; Chen, M.; Xu, L.; Yang, X. Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling. Int. J. Biol. Sci. 2022, 18 (10), 4219-4232. DOI: 10.7150/ijbs.70644.

NLM
Zuo K, Fang C, Liu Z, Fu Y, Liu Y, Liu L, Wang Y, Yin X, Liu X, Li J, Zhong J, Chen M, Xu L, Yang X. Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling. Int J Biol Sci 2022; 18(10):4219-4232. doi:10.7150/ijbs.70644. https://www.ijbs.com/v18p4219.htm

CSE
Zuo K, Fang C, Liu Z, Fu Y, Liu Y, Liu L, Wang Y, Yin X, Liu X, Li J, Zhong J, Chen M, Xu L, Yang X. 2022. Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling. Int J Biol Sci. 18(10):4219-4232.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.