Rectal microbiota are coupled with altered cytokine production capacity following community-acquired pneumonia hospitalization

Robert F J Kullberg; Xanthe Brands; Augustijn M Klarenbeek; Joe M Butler; Natasja A Otto; Daniël R Faber; Brendon P Scicluna; Tom van der Poll; W Joost Wiersinga; Bastiaan W Haak

doi:10.1016/j.isci.2022.104740

Rectal microbiota are coupled with altered cytokine production capacity following community-acquired pneumonia hospitalization

iScience. 2022 Jul 14;25(8):104740. doi: 10.1016/j.isci.2022.104740. eCollection 2022 Aug 19.

Authors

Affiliations

¹ Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, the Netherlands.
² Department of Internal Medicine, BovenIJ Hospital, Amsterdam, the Netherlands.
³ Department of Applied Biomedical Science, Faculty of Health Sciences, Mater Dei Hospital, University of Malta, Malta.
⁴ Centre for Molecular Medicine and Biobanking, University of Malta, Malta.
⁵ Division of Infectious Diseases, Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, the Netherlands.

Abstract

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.

Keywords: Immunology; Microbiology; Microbiome.