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Microbes & Immunity

REVIEW ARTICLE
Microbial involvement in myalgic

encephalomyelitis/chronic fatigue syndrome
pathophysiology

1
Alejandro Borrego-Ruiz * and Juan J. Borrego 2
1 Department of Social and Organizational Psychology, Faculty of Psychology, National University of
Distance Education (UNED), Madrid, Spain
2 Department of Microbiology, Faculty of Sciences, University of Malaga, Malaga, Spain

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and
disabling disease related to persistent fatigue, exercise intolerance, post-exertional
malaise, cognitive dysfunction, and musculoskeletal/joint pain. Gastrointestinal
comorbidities, including irritable bowel syndrome, have been reported in affected
individuals, indicating a potential role of gut microbiota in disease progression. In this
paper, bacterial and metabolomic dysbiosis in subjects with ME/CFS are reviewed,
and phenotypic, microbial, and metabolic biomarkers specific to individual cohorts
are also identified. Furthermore, microbiome fluctuations or metabolic endotoxemia
are proposed as possible disorder biomarkers. Based on the fact that gut microbiota
*Corresponding author: dysbiosis reverts to a state of eubiosis in long-term patients with this condition, it
Alejandro Borrego-Ruiz
(a.borrego@psi.uned.es) may be hypothesized that disease progression begins with the loss of beneficial
gut microorganisms, particularly short-chain fatty acid producers, leading to more
Citation:Borrego-Ruiz A, widespread gastrointestinal phenotypes that are subsequently reflected in plasma
Borrego JJ. Microbial involvement in
myalgic encephalomyelitis/chronic metabolite levels. These alterations, specific of each individual, thereby result in
fatigue syndrome pathophysiology. metabolic and phenotypic shifts and in ME/CFS.
Microbes & Immunity. 2025;2(1):17-26.
doi: 10.36922/mi.4783
Received: September 6, 2024 Keywords: Myalgic encephalomyelitis/chronic fatigue syndrome; Post-exertional
malaise; Gut microbiota; Metabolic biomarkers; Pathophysiological phenotypes
1st revised: October 22, 2024
2nd revised: November 8, 2024
Accepted: November 14, 2024
1. Introduction
Published Online: December 2,
2024 Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and
Copyright: © 2024 Author(s). disabling disease related to persistent fatigue, exercise intolerance, and other symptoms
This is an Open-Access article aggravated by physical or cognitive efforts that may manifest immediately or typically
distributed under the terms of the be delayed for hours. Prolonged exacerbation of symptoms of ME/CFS, which follows
Creative Commons Attribution
License, permitting distribution, physical activity and, in some cases, cognitive activity, is termed post-exertional malaise
and reproduction in any medium, (PEM) and may last several days. Due to this symptomatology, the quality of life of
1
provided the original work is
properly cited. people with ME/CFS is significantly restricted in terms of social and occupational
participation. 2
Publisher’s Note: AccScience
Publishing remains neutral with Despite many efforts, the etiology of ME/CFS has yet to be clarified. However,
regard to jurisdictional claims in several factors trigger the disease such as genetic predisposition, immune dysfunction,
published maps and institutional
3,4
affiliations. microbial infection, neuroendocrine imbalance, and psychological determinants.
Volume 2 Issue 1 (2025) 17 doi: 10.36922/mi.4783