Proal, Amy, Marshall, Trevor · Frontiers in pediatrics · 2018 · DOI
This review explores the idea that ME/CFS may be caused by persistent infections (like Epstein-Barr virus) that disrupt the body's microbial communities and normal cell functions. These infections can interfere with how cells work, how genes are expressed, and how the immune system responds, potentially leading to the chronic symptoms patients experience. The authors suggest that treating ME/CFS might involve helping the immune system fight these persistent infections.
This synthesis connects scattered microbiome research to ME/CFS pathophysiology, offering a unifying hypothesis that explains why different patients may have different triggers and symptom patterns. Understanding these mechanisms could guide development of targeted immune-supportive treatments rather than one-size-fits-all approaches.
This review does not provide original experimental evidence that persistent pathogens directly cause ME/CFS symptoms, nor does it establish causation versus correlation. The proposed mechanisms (molecular mimicry, metabolic interference, mitochondrial dysfunction) are discussed as plausible pathways but are not definitively demonstrated in ME/CFS populations in this article.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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Primary citation
Proal, Amy & Marshall, Trevor (2018). Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity.. Frontiers in pediatrics. https://doi.org/10.3389/fped.2018.00373
BibTeX
@article{mecfsatlas-proal-2018-myalgic-encephalomyelitis,
author = {Proal, Amy and Marshall, Trevor},
title = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity.},
journal = {Frontiers in pediatrics},
year = {2018},
doi = {10.3389/fped.2018.00373},
note = {PubMed: 30564562},
url = {https://www.mecfsatlas.com/evidence/proal-2018-myalgic-encephalomyelitis},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/proal-2018-myalgic-encephalomyelitis
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