New research reveals differences in the gut microbiomes of people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) compared to those of healthy controls.
ME/CFS is characterized by unexplained debilitating fatigue, cognitive dysfunction, gastrointestinal disturbances, among other symptoms.
The study was led by scientists at the Center for Infection and Immunity (CII) at Columbia University Mailman School of Public Health, as part of the Center for Solutions for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, an inter-disciplinary, inter-institutional research group dedicated to understanding the biology of the disease in order to develop effective means to diagnose, treat and prevent it. Findings appear in the journal Cell Host & Microbe.
The researchers conducted metagenomic and metabolomic analyses of fecal samples collected from geographically diverse cohort of 106 cases and 91 healthy controls. Results revealed differences in gut microbiome diversity, abundances, functional biological pathways, and interactions between bacteria. Cases and controls were matched for age, sex, geography, and socioeconomic status.
Gut bacteria Faecalibacterium prausnitzii and Eubacterium rectale, which are both normally abundant and health-promoting, were reduced in ME/CFS participants. For both bacteria, researchers also found a deficient microbial capacity for synthesizing butyrate, the main fuel for the body’s colon cell, with ME/CFS. The abundance of Faecalibacterium prausnitzii was inversely associated with fatigue severity.
The only other species identified with reduced relative abundance in ME/CFS was C. secundus, an acetate-producer, that could contribute to the net acetate deficiency the researchers found in ME/CFS subjects. Acetate is used by butyrate-producing bacteria to produce butyrate.
An additional nine species had increased relative abundance in ME/CFS compared to healthy controls, including C. bolteae which in other research has correlated with fatigue in multiple sclerosis. Another, R. gnavus, has been associated with inflammatory bowel disease.
“The gut microbiome is a complex ecological community teeming with diverse inter-species interactions that can be beneficial or harmful. Our research finds that in people with ME/CFS, there can be extensive rewiring of the networks of bacteria in this system,” says study senior author Brent Williams, PhD, assistant professor of epidemiology in CII at Columbia Mailman School of Public Health.
“Understanding the connection between ME/CFS and disturbances in the gut microbiome may lead to ways to classify the disease and targets for therapeutic trials,” adds co-author W. Ian Lipkin, MD, CII director and John Snow Professor of Epidemiology at Columbia Mailman School.
The study’s first author is Cheng Guo, PhD, senior programmer analyst at CII. Additional co-authors are listed in the publication.
The research was funded by the National Institutes of Health grant to the Center for Solutions for ME/CFS at Columbia University (grant number 1U54AI138370), NIH grant R56AI120724, and anonymous donors through the Crowdfunding Microbe Discovery Project.
The authors declare no competing interests.
Experts estimate there are between 800,000 and 2 million Americans with ME/CFS, a complex, debilitating disorder characterized by extreme fatigue after exertion and other symptoms including muscle and joint pain, cognitive dysfunction, sleep disturbance, and orthostatic intolerance. Currently, there is no diagnostic test for the disease; instead, patients are diagnosed based on a clinical examination and history and an exclusion of other disorders.
Prior Research on ME/CFS
In a 2017 study, CII scientists reported discovered abnormal levels of specific gut bacteria related to ME/CFS in patients with and without concurrent irritable bowel syndrome, IBS. A year later, another study identified a constellation of metabolites related to ME/CFS, providing the ability to predict whether or not someone has the disorder with a confidence of 84 percent.
In a 2015 study, CII researchers identified distinct immune changes in patients diagnosed with ME/CFS. These immune signatures represented the first robust physical evidence that ME/CFS is a biological illness as opposed to a psychological disorder, and the first evidence that the disease has distinct stages. In a 2012 study, researchers ruled out a purported link between a mouse retrovirus called XMRV and ME/CFS.