Chen Hongyu, Ding Kaiyun, Tang Cong, Xu Jingwen, Zhang Fengyuan, Yan Yao, Li Bai, Zhou Yanan, Yang Yun, Yang Hao, Huang Qing, Yu Wenhai, Wang Haixuan, Wu Daoju, Lu Shuaiyao, Liu Hongqi
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College (IMBCAMS&PUMC), Kunming, Yunnan, China.
Yunnan Province Science and Technology Department, Yunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Kunming, Yunnan, China.
Gut Microbes. 2025 Dec;17(1):2512900. doi: 10.1080/19490976.2025.2512900. Epub 2025 Jun 5.
Chikungunya virus (CHIKV) infection causes joint damage and gastrointestinal clinical symptoms, including vomiting and diarrhea, particularly in elderly populations, reflecting the potential role of gut immunity in infection. However, the mechanisms by which CHIKV induces gastrointestinal diseases remain largely unexplored. This study investigated the characteristics of fecal and gut microbiota, gut metabolites, and gut immunity post-infection using multi-omics analysis. The role of gut microbiota was further validated through Oral antibiotic depletion (Abx). Importantly, a systematic comparison of age-dependent differences in gut microbiota composition and immune responses following CHIKV infection was conducted to elucidate the involvement of gut microbiota in CHIKV pathogenesis. CHIKV joint inoculation induces gastrointestinal infection and histological damage, drives fluctuations in gut microbiota, markedly increasing the abundance of and . and upregulates conjugates of taurine and bile acids. CHIKV infection further exacerbates systemic inflammatory burden and activates intestinal interferon (IFN) signaling cascades, which supports gut repair and mucosal regeneration, but low antiviral responses to CHIKV infection compared with that of adult animals. Our results suggest that the gastrointestinal tract, along with its microbes and metabolites, modulates CHIKV infection in an age-dependent manner, providing critical insights for diagnosis, treatment, and novel therapeutic development.
基孔肯雅病毒（CHIKV）感染会导致关节损伤和胃肠道临床症状，包括呕吐和腹泻，在老年人群中尤为明显，这反映了肠道免疫在感染中的潜在作用。然而，CHIKV诱发胃肠道疾病的机制在很大程度上仍未得到探索。本研究使用多组学分析调查了感染后粪便和肠道微生物群、肠道代谢物及肠道免疫的特征。通过口服抗生素清除（Abx）进一步验证了肠道微生物群的作用。重要的是，对CHIKV感染后肠道微生物群组成和免疫反应的年龄依赖性差异进行了系统比较，以阐明肠道微生物群在CHIKV发病机制中的作用。CHIKV关节接种会诱发胃肠道感染和组织学损伤，导致肠道微生物群波动，显著增加[具体微生物名称未给出]的丰度，并上调牛磺酸和胆汁酸的结合物。CHIKV感染会进一步加重全身炎症负担，并激活肠道干扰素（IFN）信号级联反应，这有助于肠道修复和黏膜再生，但与成年动物相比，对CHIKV感染的抗病毒反应较低。我们的结果表明，胃肠道及其微生物和代谢物以年龄依赖性方式调节CHIKV感染，为诊断、治疗和新型疗法的开发提供了关键见解。
