南方医科大学Shenhai Gong，Yong Jiang和Wei Xiao共同合作，近期取得重要工作进展。他们研究发现妊娠引起的肠道菌群变化驱动巨噬细胞焦亡并加剧脓毒性炎症。相关研究成果2023年2月14日在线发表于《免疫》杂志上。

据介绍，怀孕期间发生的生理和免疫变化与感染和败血症期间疾病结果恶化有关。这些扰动是如何加剧炎症的，目前还没有研究。

使用抗生素治疗和粪便微生物转移，研究人员发现败血症易感性是由妊娠引起的小鼠和人类肠道微生物组的变化驱动的。综合多组学和基因工程细菌研究表明，妊娠期拟副杆菌（P.merdae）的丰度降低导致了福尔摩罗宁（FMN）的降低和巨噬细胞死亡的增加。从机制上讲，FMN通过抑制hnRNPUL2的核积累以及随后与Nlrp3启动子的结合来抑制巨噬细胞焦亡。用FMN治疗或敲除小鼠hnRNPUL2可防止感染性炎症。P. merdae和FMN的肠道丰度与脓毒性患者的进展呈负相关。

总之，这一数据揭示了在妊娠脓毒症宿主中被破坏的微生物免疫途径，突出了FMN-hnRNPUL2-NLRP3轴在提供脓毒症治疗策略方面的潜力。

附：英文原文

Title: Pregnancy-induced changes to the gut microbiota drive macrophage pyroptosis and exacerbate septic inflammation

Author: Xia Chen, Rong Wu, Lei Li, Yunong Zeng, Jingrui Chen, Mingyuan Wei, Yinglin Feng, Guiming Chen, Yuhang Wang, Lizhen Lin, Haihua Luo, Ali Chen, Zhenhua Zeng, Fangjie He, Yang Bai, Siyou Zhang, Yubing Han, Zhang Wang, Xiaoshan Zhao, Wei Xiao, Yong Jiang, Shenhai Gong

Issue&Volume: 2023/02/14

Abstract: The physiological and immune changes that occur during pregnancy are associated withworsened disease outcomes during infection and sepsis. How these perturbations exacerbateinflammation has not been explored. Here, using antibiotic treatment and fecal microbialtransfers, we showed that sepsis susceptibility is driven by pregnancy-induced changesto gut microbiome in mice and humans. Integrative multiomics and genetically engineeredbacteria revealed that reduced Parabacteroides merdae (P. merdae) abundance during pregnancy led to decreased formononetin (FMN) and increased macrophagedeath. Mechanistically, FMN inhibited macrophage pyroptosis by suppressing nuclearaccumulation of hnRNPUL2 and subsequent binding to the Nlrp3 promoter. Treatment with FMN or deletion of murine hnRNPUL2 protected against septicinflammation. Intestinal abundances of P. merdae and FMN inversely correlated with the progression of septic patients. Our data reveala microbe-immune axis that is disrupted in pregnant septic hosts, highlighting thepotential of the FMN-hnRNPUL2-NLRP3 axis in providing promising therapeutic strategiesfor sepsis.

DOI: 10.1016/j.immuni.2023.01.015

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00025-0