多重耐药菌定植和感染的危重症患者的肠道微生物群失调与全身免疫功能障碍

Gut microbiota dysbiosis and systemic immune dysfunction in critical ill patients with multidrug-resistant bacterial colonization and infection.

作者信息

Ling Zongxin, Ding Wenwen, Liu Xia, Zhang Jingchen, Cheng Yiwen, Zhu Zhangcheng, Wu Lingbin, Xu Xiaocui, Gao Yongtao, Jiang Ruilai

机构信息

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory On Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China.

Yuhang Institute for Collaborative Innovation and Translational Research in Life Sciences and Technology, Hangzhou, 310000, Zhejiang, China.

出版信息

J Transl Med. 2025 Sep 2;23(1):981. doi: 10.1186/s12967-025-07049-2.

DOI:10.1186/s12967-025-07049-2

PMID:40898347

Abstract

BACKGROUND

Antimicrobial resistance (AMR) poses a global health threat, particularly in critically ill patients with multidrug-resistant organism (MDRO) colonization or infection. While evidence suggests the gut microbiota plays a critical role in MDRO colonization and infection, its specific characteristics and the host immune response remain poorly understood.

METHODS AND RESULTS

This case-control study compared 88 MDRO-infected patients, 100 MDRO-colonized patients, and 86 healthy controls, using 16S rRNA sequencing and cytokine profiling. MDRO cohorts exhibited profound gut dysbiosis, including reduced gut microbial diversity and distinct community structures, reduced beneficial bacteria (e.g., Bacteroides, Faecalibacterium, Roseburia, Prevotella), and expansion of pathobionts-resident microbes with pathogenic potential (e.g., Enterococcus, Klebsiella, Escherichia-Shigella). Enterotype analysis revealed a shift from a Bacteroides-dominated to one Enterococcus-dominated microbiota in both colonized and infected patients compared to controls. Serum cytokine profiling indicated immune dysfunction in MDRO-associated patients. Correlation analysis showed that beneficial genera were negatively correlated with pro-inflammatory cytokines (IL-1ra, IL-2, IL-7, TNF-α, and IFN-γ) and positively associated with anti-inflammatory markers, while pathobionts exhibited the opposite trend. Several key differential genera, such as Enterococcus and Klebsiella, either individually or in combination, have been identified as key discriminators of MDRO status. Functional predictions through PiCRUSt observed disruptions in carbohydrate and lipid metabolism in the MDRO cohorts.

CONCLUSION

Overall, MDRO colonization and infection lead to gut dysbiosis and immune dysfunction, with microbiota-immune interactions playing a crucial role in disease progression, suggesting the gut microbiota as a potential diagnostic and therapeutic target for AMR.

摘要

背景

抗菌药物耐药性（AMR）对全球健康构成威胁，尤其是在多重耐药菌（MDRO）定植或感染的重症患者中。虽然有证据表明肠道微生物群在MDRO定植和感染中起关键作用，但其具体特征和宿主免疫反应仍知之甚少。

方法与结果

本病例对照研究使用16S rRNA测序和细胞因子谱分析，比较了88例MDRO感染患者、100例MDRO定植患者和86例健康对照。MDRO队列表现出严重的肠道生态失调，包括肠道微生物多样性降低和群落结构不同，有益细菌（如拟杆菌属、粪杆菌属、罗氏菌属、普雷沃菌属）减少，以及具有致病潜力的潜在致病微生物（如肠球菌属、克雷伯菌属、大肠埃希菌-志贺菌属）扩张。肠型分析显示，与对照组相比，定植和感染患者的微生物群从以拟杆菌属为主转变为以肠球菌属为主。血清细胞因子谱分析表明MDRO相关患者存在免疫功能障碍。相关性分析显示，有益菌属与促炎细胞因子（IL-1ra、IL-2、IL-7、TNF-α和IFN-γ）呈负相关，与抗炎标志物呈正相关，而潜在致病微生物则呈现相反趋势。已确定几种关键的差异菌属，如肠球菌属和克雷伯菌属，单独或联合起来，可作为MDRO状态的关键判别指标。通过PiCRUSt进行的功能预测发现，MDRO队列中的碳水化合物和脂质代谢存在紊乱。