Extracellular vesicles produced by the human commensal gut bacterium Bacteroides thetaiotaomicron affect host immune pathways in a cell-type specific manner that are altered in inflammatory bowel disease

Gul, Lejla, Modos, Dezso, Fonseca, Sonia, Madgwick, Matthew, Thomas, John P., Sudhakar, Padhmanand, Booth, Catherine, Stentz, Régis, Carding, Simon R. and Korcsmaros, Tamas (2022) Extracellular vesicles produced by the human commensal gut bacterium Bacteroides thetaiotaomicron affect host immune pathways in a cell-type specific manner that are altered in inflammatory bowel disease. Journal of Extracellular Vesicles, 11 (1). ISSN 2001-3078

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Abstract

The gastrointestinal (GI) tract harbours a complex microbial community, which contributes to its homeostasis. A disrupted microbiome can cause GI-related diseases, including inflammatory bowel disease (IBD), therefore identifying host-microbe interactions is crucial for better understanding gut health. Bacterial extracellular vesicles (BEVs), released into the gut lumen, can cross the mucus layer and access underlying immune cells. To study BEV-host interactions, we examined the influence of BEVs generated by the gut commensal bacterium, Bacteroides thetaiotaomicron, on host immune cells. Single-cell RNA sequencing data and host-microbe protein-protein interaction networks were used to predict the effect of BEVs on dendritic cells, macrophages and monocytes focusing on the Toll-like receptor (TLR) pathway. We identified biological processes affected in each immune cell type and cell-type specific processes including myeloid cell differentiation. TLR pathway analysis highlighted that BEV targets differ among cells and between the same cells in healthy versus disease (ulcerative colitis) conditions. The in silico findings were validated in BEV-monocyte co-cultures demonstrating the requirement for TLR4 and Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP) in BEV-elicited NF-kB activation. This study demonstrates that both cell-type and health status influence BEV-host communication. The results and the pipeline could facilitate BEV-based therapies for the treatment of IBD.

Item Type: Article
Additional Information: Research Funding: UKRI Biotechnological and Biosciences Research Council (BBSRC). Grant Numbers: BB/J004529/1, BB/P016774/1, BB/CSP17270/1; Quadram Institute's Gut Microbes and Health Institute Strategic Programme. Grant Numbers: BB/R012490/1, BBS/E/F/000PR10353, BBS/E/F/000PR10355; BBSRC Norwich Research Park Biosciences Doctoral Training Partnership. Grant Number: BB/M011216/1; the National Institute of Health Research (NIHR)
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 16 Feb 2022 16:30
Last Modified: 12 May 2022 00:31
URI: https://ueaeprints.uea.ac.uk/id/eprint/83535
DOI: 10.1002/jev2.12189

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