Wang Jiaqi, Yin Jiali, Liu Xiaolei, Liu Yi, Jin Xuemin
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China.
College of Animal Sciences, Jilin University, Changchun, China.
PLoS Pathog. 2025 Apr 16;21(4):e1013069. doi: 10.1371/journal.ppat.1013069. eCollection 2025 Apr.
Trichinella spiralis (Ts) is known to cause cardiac fibrosis, which is a critical precursor to various heart diseases, and its progression is influenced by metabolic changes. However, the metabolic mechanisms remain unclear. Here, we observed that Ts-infected mice exhibited cardiac fibrosis along with elevated succinate levels in the heart using metabolomic analysis. Administration of succinate exacerbated fibrosis during Ts infection, while deficiency in succinate receptor 1 (Sucnr1) alleviated the condition, highlighting the role of the succinate-Sucnr1 axis in fibrosis development. Furthermore, metagenomics sequencing showed that Ts-infected mice had a higher abundance ratio of succinate-producing bacteria to succinate-consuming bacteria in the intestines. Notably, the succinate-producer Bacteroides vulgatus was enriched in Ts group. Oral supplementation with B. vulgatus aggravated Ts-induced cardiac fibrosis. In summary, our findings underscore the succinate-Sucnr1 axis as a critical pathway in helminth-induced cardiac fibrosis and highlight the potential of targeting this axis for therapeutic interventions. This study presents novel insights into the gut-heart axis, revealing innovative strategies for managing cardiovascular complications associated with helminth infections.
旋毛虫（Trichinella spiralis，Ts）已知会导致心脏纤维化，这是各种心脏病的关键先兆，其进展受代谢变化影响。然而，代谢机制仍不清楚。在此，我们通过代谢组学分析观察到，感染旋毛虫的小鼠心脏出现纤维化，同时心脏中琥珀酸水平升高。在旋毛虫感染期间，给予琥珀酸会加剧纤维化，而琥珀酸受体1（Sucnr1）缺乏则会缓解这种情况，这突出了琥珀酸-Sucnr1轴在纤维化发展中的作用。此外，宏基因组测序显示，感染旋毛虫的小鼠肠道中产生琥珀酸的细菌与消耗琥珀酸的细菌的丰度比更高。值得注意的是，产琥珀酸的脆弱拟杆菌在旋毛虫组中富集。口服补充脆弱拟杆菌会加重旋毛虫诱导的心脏纤维化。总之，我们的研究结果强调了琥珀酸-Sucnr1轴是蠕虫诱导心脏纤维化的关键途径，并突出了针对该轴进行治疗干预的潜力。本研究为肠-心轴提供了新的见解，揭示了管理与蠕虫感染相关的心血管并发症的创新策略。
