Cargando…

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

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 determin...

Descripción completa

Detalles Bibliográficos
Autores principales: Zuo, Kun, Fang, Chen, Liu, Zheng, Fu, Yuan, Liu, Ye, Liu, Lifeng, Wang, Yuxing, Yin, Xiandong, Liu, Xiaoqing, Li, Jing, Zhong, Jiuchang, Chen, Mulei, Xu, Li, Yang, Xinchun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274492/
https://www.ncbi.nlm.nih.gov/pubmed/35844801
http://dx.doi.org/10.7150/ijbs.70644
_version_ 1784745315982639104
author Zuo, Kun
Fang, Chen
Liu, Zheng
Fu, Yuan
Liu, Ye
Liu, Lifeng
Wang, Yuxing
Yin, Xiandong
Liu, Xiaoqing
Li, Jing
Zhong, Jiuchang
Chen, Mulei
Xu, Li
Yang, Xinchun
author_facet Zuo, Kun
Fang, Chen
Liu, Zheng
Fu, Yuan
Liu, Ye
Liu, Lifeng
Wang, Yuxing
Yin, Xiandong
Liu, Xiaoqing
Li, Jing
Zhong, Jiuchang
Chen, Mulei
Xu, Li
Yang, Xinchun
author_sort Zuo, Kun
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9274492
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Ivyspring International Publisher
record_format MEDLINE/PubMed
spelling pubmed-92744922022-07-15 Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling Zuo, Kun Fang, Chen Liu, Zheng Fu, Yuan Liu, Ye Liu, Lifeng Wang, Yuxing Yin, Xiandong Liu, Xiaoqing Li, Jing Zhong, Jiuchang Chen, Mulei Xu, Li Yang, Xinchun Int J Biol Sci Research Paper 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. Ivyspring International Publisher 2022-06-27 /pmc/articles/PMC9274492/ /pubmed/35844801 http://dx.doi.org/10.7150/ijbs.70644 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Research Paper
Zuo, Kun
Fang, Chen
Liu, Zheng
Fu, Yuan
Liu, Ye
Liu, Lifeng
Wang, Yuxing
Yin, Xiandong
Liu, Xiaoqing
Li, Jing
Zhong, Jiuchang
Chen, Mulei
Xu, Li
Yang, Xinchun
Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling
title Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling
title_full Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling
title_fullStr Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling
title_full_unstemmed Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling
title_short Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling
title_sort commensal microbe-derived scfa alleviates atrial fibrillation via gpr43/nlrp3 signaling
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274492/
https://www.ncbi.nlm.nih.gov/pubmed/35844801
http://dx.doi.org/10.7150/ijbs.70644
work_keys_str_mv AT zuokun commensalmicrobederivedscfaalleviatesatrialfibrillationviagpr43nlrp3signaling
AT fangchen commensalmicrobederivedscfaalleviatesatrialfibrillationviagpr43nlrp3signaling
AT liuzheng commensalmicrobederivedscfaalleviatesatrialfibrillationviagpr43nlrp3signaling
AT fuyuan commensalmicrobederivedscfaalleviatesatrialfibrillationviagpr43nlrp3signaling
AT liuye commensalmicrobederivedscfaalleviatesatrialfibrillationviagpr43nlrp3signaling
AT liulifeng commensalmicrobederivedscfaalleviatesatrialfibrillationviagpr43nlrp3signaling
AT wangyuxing commensalmicrobederivedscfaalleviatesatrialfibrillationviagpr43nlrp3signaling
AT yinxiandong commensalmicrobederivedscfaalleviatesatrialfibrillationviagpr43nlrp3signaling
AT liuxiaoqing commensalmicrobederivedscfaalleviatesatrialfibrillationviagpr43nlrp3signaling
AT lijing commensalmicrobederivedscfaalleviatesatrialfibrillationviagpr43nlrp3signaling
AT zhongjiuchang commensalmicrobederivedscfaalleviatesatrialfibrillationviagpr43nlrp3signaling
AT chenmulei commensalmicrobederivedscfaalleviatesatrialfibrillationviagpr43nlrp3signaling
AT xuli commensalmicrobederivedscfaalleviatesatrialfibrillationviagpr43nlrp3signaling
AT yangxinchun commensalmicrobederivedscfaalleviatesatrialfibrillationviagpr43nlrp3signaling