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ToolsSeton, Katharine A., Defernez, Marianne, Telatin, Andrea, Tiwari, Sumeet K., Savva, George M., Hayhoe, Antonietta, Noble, Alistair, de Carvalho-KoK, Ana L. S., James, Steve A., Bansal, Amolak, Wileman, Thomas and Carding, Simon R. (2023) Investigating antibody reactivity to the intestinal microbiome in severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): A feasibility study. International Journal of Molecular Sciences, 24 (20). ISSN 1661-6596
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Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystemic disease of unknown aetiology that is characterised by disabling chronic fatigue and involves both the immune and gastrointestinal (GI) systems. Patients display alterations in GI microbiome with a significant proportion experiencing GI discomfort and pain and elevated blood biomarkers for altered intestinal permeability compared with healthy individuals. To investigate a possible GI origin of ME/CFS we designed a feasibility study to test the hypothesis that ME/CFS pathogenesis is a consequence of increased intestinal permeability that results in microbial translocation and a breakdown in immune tolerance leading to generation of antibodies reactive to indigenous intestinal microbes. Secretory immunoglobulin (Ig) A and serum IgG levels and reactivity to intestinal microbes were assessed in five pairs of severe ME/CFS patients and matched same-household healthy controls. For profiling serum IgG, we developed IgG-Seq which combines flow-cytometry based bacterial cell sorting and metagenomics to detect mucosal IgG reactivity to the microbiome. We uncovered evidence for immune dysfunction in severe ME/CFS patients that was characterised by reduced capacity and reactivity of serum IgG to stool microbes, irrespective of their source. This study provides the rationale for additional studies in larger cohorts of ME/CFS patients to further explore immune–microbiome interactions.
| Item Type: | Article |
|---|---|
| Additional Information: | Data Availability Statement: The raw data are available at the European Nucleotide Archive under study accession number PRJEB1661 (http://www.ebi.ac.uk/ena/browser/view?PRJEB61661, accessed on 27 April 2023). Funding Information: This research was joint funded by the UK charity Invest in ME Research (charity number 1153730) and the University of East Anglia (S.R.C.) with support from the Biological Sciences Research Council (BBSRC) Institute Strategic Programme Grant Gut Microbes and Health BB/R012490/1 and its constituent projects BBS/E/F/000PR10353, BBS/E/F/000PR10355 and BBS/E/F/000PR10356 (S.R.C.) and by the BBSRC Core Capability Grant BB/CCG1860/1 (G.M.S. and M.D.). |
| Uncontrolled Keywords: | antibodies,autologous,heterologous,immune tolerance,immunoglobulin a,immunoglobulin g,leaky gut,microbiome,cfs),catalysis,molecular biology,spectroscopy,computer science applications,physical and theoretical chemistry,organic chemistry,inorganic chemistry ,/dk/atira/pure/subjectarea/asjc/1500/1503 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Population Health Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging |
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| Depositing User: | LivePure Connector |
| Date Deposited: | 31 Oct 2024 15:30 |
| Last Modified: | 01 Nov 2024 11:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97390 |
| DOI: | 10.3390/ijms242015316 |
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