Signature microbiome disturbances in ME/CFS may point to biomarker and treatment trials

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 a debilitating disease that affects approximately 1.5 million people in the U.S. At least one-quarter of ME/CFS patients are house or bedbound at some point in their lives, and approximately half are unemployed. ME/CFS is characterized by disabling fatigue that is not relieved with rest, post-exertional malaise, insomnia, brain fog, muscle pain, and gastrointestinal issues. There are no diagnostic tests or FDA-approved treatments.  ME/CFS is the archetypal chronic post-viral illness and is clinically similar to post-COVID-19 syndrome or Long COVID.

Bateman Horne Center (BHC) located in Salt Lake City, Utah, served as the Clinical Core for The Jackson Laboratory (JAX) and was one of five clinical sites that recruited patients for Columbia University’s Center for Solutions for ME/CFS. BHC screened over 500 patients to identify 150 patients that met the strict criteria for participation in these studies. All patients that qualified received a comprehensive medical history review and evaluation and provided blood and stool samples several times over four years. This type of patient participation is heroic for a disease that leaves most patients drained of energy, and only having a couple of hours of activity tolerance a day. ME/CFS is also vastly underdiagnosed.

Today, some of the fruits of our ME/CFS patients’ participation is published in two important papers in the journal of Cell Host & Microbe. Both papers reveal significant differences in the microbiome diversity, abundance, and functional biological pathways of research participants with ME/CFS compared to healthy controls. They validate similar findings from previous studies, identify potential biomarkers, and point toward a path for ME/CFS treatment trials.

BHC Medical Director, Lucinda Bateman, MD, says, “We partnered with JAX in 2017 to submit this NIH grant application with the specific goal of enrolling ME/CFS research subjects in the early stages of illness.  This is one of the largest studies of ME/CFS, especially from a single clinical site and provides important evidence that lays the foundation for clinical trials. It was challenging to find patients early in illness, because accurate diagnosis often takes years, but recognition of post-viral syndromes, especially ME/CFS, is improving.  Thank you to everyone who participated.”

Microbiome and metabolomic results are described in “Multi-‘omics of host-microbiome interactions in short- and long-term Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).” The JAX team analyzed data for two distinct ME/CFS cohorts including 75 newly diagnosed patients sick with ME/CFS for <4 years and 79 ME/CFS patients sick for >10 years. Microbiome metagenomic analysis showed that the <4 year ME/CFS cohort had more microbial dysbiosis, while the > 10 year ME/CFS cohorts’ microbiome was more like healthy controls. However, the >10 year ME/CFS patients had more severe disease presentation including pain and sleep problems and metabolic abnormalities.

The microbiome was the focus of the paper titled, “Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS.” The laboratory team at the Center for ME/CFS Solutions analyzed stool samples from 106 ME/CFS cases and 91 health controls that were recruited from five ME/CFS clinics across the US (NV, FL, NY, CA, UT). The metagenomic and metabolic analyses findings indicate that gut bacteria Faecalibacterium prausnitzii and Eubacterium rectale, which are both normally abundant and health-promoting, were reduced in ME/CFS participants. Loss of these important bacteria in individuals with ME/CFS contributed to deficient microbial capacity for synthesizing butyrate, a multifunctional bacterial metabolite with anti-inflammatory properties and the main fuel for the body’s colon cells. The abundance of Faecalibacterium prausnitzii was inversely associated with fatigue severity in ME/CFS, providing a direct link between the microbiome and disease symptoms.

This research was funded by the National Institutes of Health (NIH) with grants to the Center for Solutions for ME/CFS at Columbia University (grant number 1U54A138370) and The Jackson Laboratory (grant number 1U54NS105539).

The Bateman Horne Center is a non-profit interdisciplinary Center of Excellence where clinical care, research, and education meet to collectively advance the diagnosis and treatment of ME/CFS, fibromyalgia, post-viral syndromes, and related comorbidities.