Kullberg Robert F J, Brands Xanthe, Klarenbeek Augustijn M, Butler Joe M, Otto Natasja A, Faber Daniël R, Scicluna Brendon P, van der Poll Tom, Wiersinga W Joost, Haak Bastiaan W
Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, the Netherlands.
Department of Internal Medicine, BovenIJ Hospital, Amsterdam, the Netherlands.
iScience. 2022 Jul 14;25(8):104740. doi: 10.1016/j.isci.2022.104740. eCollection 2022 Aug 19.
Human studies describing the immunomodulatory role of the intestinal microbiota in systemic infections are lacking. Here, we sought to relate microbiota profiles from 115 patients with community-acquired pneumonia (CAP), both on hospital admission and following discharge, to concurrent circulating monocyte and neutrophil function. Rectal microbiota composition did not explain variation in cytokine responses in acute CAP (median 0%, IQR 0.0%-1.9%), but did one month following hospitalization (median 4.1%, IQR 0.0%-6.6%, p = 0.0035). Gene expression analysis of monocytes showed that undisrupted microbiota profiles following hospitalization were associated with upregulated interferon, interleukin-10, and G-protein-coupled-receptor-ligand-binding pathways. While CAP is characterized by profoundly distorted gut microbiota, the effects of these disruptions on cytokine responses and transcriptional profiles during acute infection were absent or modest. However, rectal microbiota were related to altered cytokine responses one month following CAP hospitalization, which may provide insights into potential mechanisms contributing to the high risk of recurrent infections following hospitalization.
目前尚缺乏关于肠道微生物群在全身感染中的免疫调节作用的人体研究。在此，我们试图将115例社区获得性肺炎（CAP）患者在入院时和出院后的微生物群谱与同时期循环单核细胞和中性粒细胞功能联系起来。直肠微生物群组成并不能解释急性CAP中细胞因子反应的变化（中位数为0%，四分位间距为0.0%-1.9%），但在住院后一个月可以解释（中位数为4.1%，四分位间距为0.0%-6.6%，p = 0.0035）。单核细胞的基因表达分析表明，住院后未受干扰的微生物群谱与干扰素、白细胞介素-10和G蛋白偶联受体配体结合途径的上调有关。虽然CAP的特征是肠道微生物群严重失调，但这些失调对急性感染期间细胞因子反应和转录谱的影响不存在或较小。然而，直肠微生物群与CAP住院后一个月细胞因子反应的改变有关，这可能为住院后反复感染高风险的潜在机制提供见解。
