The "Biology-First" Hypothesis: Functional disorders may begin and end with biology-A scoping review.
Enck, P, Mazurak, N · Neurogastroenterology and motility · 2018 · DOI
Quick Summary
This study reviewed research showing that infections can trigger long-lasting functional disorders—conditions where the body doesn't work properly but standard tests appear normal. The authors propose that these disorders start from biological changes (like immune dysfunction or altered gut bacteria) caused by the infection, and that psychological factors develop as a result rather than being the root cause. This challenges the common belief that such conditions are mainly psychological or social in nature.
Why It Matters
For ME/CFS patients and researchers, this framework is significant because ME/CFS often follows viral infections and presents as a functional disorder with multisystem symptoms. The study supports investigating underlying biological mechanisms—immune dysregulation, mitochondrial dysfunction, microbiome changes—rather than attributing symptoms primarily to psychological factors, which may redirect research and clinical attention toward treatable biological causes.
Observed Findings
Gastrointestinal infections can trigger both intestinal functional disorders (PI-IBS, PI-FD) and non-intestinal functional disturbances
Non-intestinal infections can provoke both intestinal and non-intestinal functional symptoms
Medically unexplained functional symptoms often persist long-term after infection
Multiple organ systems can be affected in postinfectious functional syndromes
Genetic, endocrine, and microbiological factors are implicated in postinfectious functional disease
Inferred Conclusions
Functional disorders following infection may have primarily biological origins (genetic, endocrine, microbiological) rather than being primarily psychosomatic
Psychological and social factors contribute to the disease phenotype but are secondary to underlying biological dysfunction
The search for psychological explanations of postinfectious functional disorders may be misleading and should be deprioritized in favor of biological investigation
The biopsychosocial model should be reframed to begin with biology as the foundation
Remaining Questions
What specific biological mechanisms (immune markers, microbiome signatures, genetic variants) distinguish patients who develop chronic postinfectious functional disorders from those who recover?
What This Study Does Not Prove
This scoping review does not establish causation or provide new experimental data; it synthesizes existing literature and proposes a hypothesis rather than testing it. It does not prove that psychological factors play no role in disease expression or prognosis, only that they may be secondary rather than primary. The applicability to ME/CFS specifically is not directly addressed and would require targeted investigation.
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 →