{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:12Z","timestamp":1787028552418,"version":"build-2736575974"},"reference-count":230,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MRC","award":["MR\/K000551\/1"],"award-info":[{"award-number":["MR\/K000551\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Clostridioides difficile (C. difficile) is a global threat and has significant implications for individuals and health care systems. Little is known about host molecular mechanisms and transcriptional changes in peripheral immune cells. This is the first gene expression study in whole blood from patients with C. difficile infection. We took blood and stool samples from patients with toxigenic C. difficile infection (CDI), non-toxigenic C. difficile infection (GDH), inflammatory bowel disease (IBD), diarrhea from other causes (DC), and healthy controls (HC). We performed transcriptome-wide RNA profiling on peripheral blood to identify diarrhea common and CDI unique gene sets. Diarrhea groups upregulated innate immune responses with neutrophils at the epicenter. The common signature associated with diarrhea was non-specific and shared by various other inflammatory conditions. CDI had a unique 45 gene set reflecting the downregulation of humoral and T cell memory functions. Dysregulation of immunometabolic genes was also abundant and linked to immune cell fate during differentiation. Whole transcriptome analysis of white cells in blood from patients with toxigenic C. difficile infection showed that there is an impairment of adaptive immunity and immunometabolism.<\/jats:p>","DOI":"10.3390\/ijms252312653","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T09:59:34Z","timestamp":1732528774000},"page":"12653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Gene Expression Dysregulation in Whole Blood of Patients with Clostridioides difficile Infection"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7946-3953","authenticated-orcid":false,"given":"Maria","family":"Tsakiroglou","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Institute of Systems Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8547-1730","authenticated-orcid":false,"given":"Anthony","family":"Evans","sequence":"additional","affiliation":[{"name":"Computational Biology Facility, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1502-0184","authenticated-orcid":false,"given":"Alejandra","family":"Doce-Carracedo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Institute of Systems Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GL, UK"},{"name":"Clinical Directorate, GCP Laboratories, University of Liverpool, Liverpool L7 8TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Little","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Institute of Systems Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Hornby","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Institute of Systems Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Institute of Systems Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GL, UK"},{"name":"Faculty of Science and Engineering, School of Biomedical Science and Physiology, University of Wolverhampton, Wolverhampton WV1 1LZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunice","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Institute of Systems Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Miyajima","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Institute of Systems Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GL, UK"},{"name":"Oswaldo Cruz Foundation (Fiocruz), Branch Ceara, Eusebio 61773-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7534-7266","authenticated-orcid":false,"given":"Munir","family":"Pirmohamed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Institute of Systems Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"010407","DOI":"10.7189\/jogh.09.010407","article-title":"Global burden of Clostridium difficile infections: A systematic review and meta-analysis","volume":"9","author":"Balsells","year":"2019","journal-title":"J. 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