Laboratory of Animal Neurobiology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
Institute of Veterinary Medicine, Xinjiang Academy of Animal Science, Urumqi, 830013, China.
Appl Microbiol Biotechnol. 2024 Sep 19;108(1):469. doi: 10.1007/s00253-024-13280-6.
Prior research has indicated that the gut-lung-axis can be influenced by the intestinal microbiota, thereby impacting lung immunity. Rifaximin is a broad-spectrum antibacterial drug that can maintain the homeostasis of intestinal microflora. In this study, we established an influenza A virus (IAV)-infected mice model with or without rifaximin supplementation to investigate whether rifaximin could ameliorate lung injury induced by IAV and explore the molecular mechanism involved. Our results showed that IAV caused significant weight loss and disrupted the structure of the lung and intestine. The analysis results of 16S rRNA and metabolomics indicated a notable reduction in the levels of probiotics Lachnoclostridium, Ruminococcaceae_UCG-013, and tryptophan metabolites in the fecal samples of mice infected with IAV. In contrast, supplementation with 50 mg/kg rifaximin reversed these changes, including promoting the repair of the lung barrier and increasing the abundance of Muribaculum, Papillibacter and tryptophan-related metabolites content in the feces. Additionally, rifaximin treatment increased ILC3 cell numbers, IL-22 level, and the expression of RORγ and STAT-3 protein in the lung. Furthermore, our findings demonstrated that the administration of rifaximin can mitigate damage to the intestinal barrier while enhancing the expression of AHR, IDO-1, and tight junction proteins in the small intestine. Overall, our results provided that rifaximin alleviated the imbalance in gut microbiota homeostasis induced by IAV infection and promoted the production of tryptophan-related metabolites. Tryptophan functions as a signal to facilitate the activation and movement of ILC3 cells from the intestine to the lung through the AHR/STAT3/IL-22 pathway, thereby aiding in the restoration of the barrier. KEY POINTS: • Rifaximin ameliorated IAV infection-caused lung barrier injury and induced ILC3 cell activation. • Rifaximin alleviated IAV-induced gut dysbiosis and recovered tryptophan metabolism. • Tryptophan mediates rifaximin-induced ILC3 cell activation via the AHR/STAT3/IL-22 pathway.
先前的研究表明，肠道-肺轴可以受到肠道微生物群的影响，从而影响肺部免疫。利福昔明是一种广谱抗菌药物，可以维持肠道微生物群的平衡。在这项研究中，我们建立了一个流感病毒（IAV）感染的小鼠模型，并用或不用利福昔明补充剂来研究利福昔明是否可以改善 IAV 引起的肺损伤，并探讨涉及的分子机制。我们的结果表明，IAV 导致显著的体重减轻和肺和肠道结构的破坏。16S rRNA 和代谢组学的分析结果表明，感染 IAV 的小鼠粪便中益生菌lachnoclostridium、ruminococcaceae_ucg-013 和色氨酸代谢物的水平显著降低。相比之下，50mg/kg 利福昔明的补充逆转了这些变化，包括促进肺屏障的修复和增加muribaculum、papillibacter 和色氨酸相关代谢物含量在粪便中的丰度。此外，利福昔明治疗增加了 ILC3 细胞数量、IL-22 水平以及肺中 RORγ 和 STAT-3 蛋白的表达。此外，我们的研究结果表明，利福昔明的给药可以减轻肠道屏障的损伤，同时增强小肠中 AHR、IDO-1 和紧密连接蛋白的表达。总的来说，我们的研究结果表明，利福昔明减轻了 IAV 感染引起的肠道微生物群平衡失调，并促进了色氨酸相关代谢物的产生。色氨酸作为一种信号，通过 AHR/STAT3/IL-22 途径促进 ILC3 细胞从肠道向肺的激活和运动，从而有助于恢复屏障。关键点： •利福昔明改善了 IAV 感染引起的肺屏障损伤和诱导 ILC3 细胞的激活。 •利福昔明减轻了 IAV 引起的肠道功能障碍并恢复了色氨酸代谢。 •色氨酸通过 AHR/STAT3/IL-22 途径介导利福昔明诱导的 ILC3 细胞激活。
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