Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease

Front Immunol. 2024 Jun 3:15:1386607. doi: 10.3389/fimmu.2024.1386607. eCollection 2024.

Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, debilitating disease characterised by a wide range of symptoms that severely impact all aspects of life. Despite its significant prevalence, ME/CFS remains one of the most understudied and misunderstood conditions in modern medicine. ME/CFS lacks standardised diagnostic criteria owing to variations in both inclusion and exclusion criteria across different diagnostic guidelines, and furthermore, there are currently no effective treatments available. Moving beyond the traditional fragmented perspectives that have limited our understanding and management of the disease, our analysis of current information on ME/CFS represents a significant paradigm shift by synthesising the disease's multifactorial origins into a cohesive model. We discuss how ME/CFS emerges from an intricate web of genetic vulnerabilities and environmental triggers, notably viral infections, leading to a complex series of pathological responses including immune dysregulation, chronic inflammation, gut dysbiosis, and metabolic disturbances. This comprehensive model not only advances our understanding of ME/CFS's pathophysiology but also opens new avenues for research and potential therapeutic strategies. By integrating these disparate elements, our work emphasises the necessity of a holistic approach to diagnosing, researching, and treating ME/CFS, urging the scientific community to reconsider the disease's complexity and the multifaceted approach required for its study and management.

Keywords: diagnostic criteria; myalgic encephalomyelitis/chronic fatigue syndrome; pathology; pathophysiology; treatment.

Publication types

  • Review

MeSH terms

  • Animals
  • Dysbiosis
  • Fatigue Syndrome, Chronic* / diagnosis
  • Fatigue Syndrome, Chronic* / etiology
  • Fatigue Syndrome, Chronic* / immunology
  • Fatigue Syndrome, Chronic* / therapy
  • Gastrointestinal Microbiome / immunology
  • Humans
  • Neglected Diseases

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. HA thanks the Harry Crossley Foundation for research funding. DK thanks the Novo Nordisk Foundation for funding (grant NNF20CC0035580) and Balvi (grant 18). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. EP thanks the NRF of South Africa (grant number 142142) and SA MRC (self-initiated research (SIR) grant). The content and findings reported and illustrated are the sole deduction, view and responsibility of the researchers and do not reflect the official position and sentiments of the funders.