Chronic Fatigue Syndrome Patients Have Altered Gut Microbiota

A new study has explored changes to the gut microbiome in people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The study’s unique design shows the long-term effects of ME/CFS and identifies a group of microbes associated with the disease’s pathology.

The microbiome and ME/CFS

ME/CFS is a disabling illness that is thought to affect up to 2.5 million Americans, although 9 in 10 remain undiagnosed. The condition produces a range of functional impairments and cognitive symptoms, including overwhelming fatigue, sleep disruption, difficulty concentrating, dizziness and pain. The disease, long overlooked by medical authorities, has been increasingly recognized due to its similarities to the effects of long-COVID. Research into possible links to viral infection and the role of the immune system in the disease’s pathology has ramped up.

The community of microbes living in our bodies – the microbiome – is closely connected to how we respond to infection and our immune system’s function. To investigate how our microbiota may be disrupted by ME/CFS, a team based at the Jackson Laboratory and led by Associate Professor Julia Oh used powerful sequencing and multiomics technologies to interrogate gut bacteria.

The research was published in Cell Host & Microbes.

ME/CFS: A complex condition

ME/CFS’s heterogeneity is one of the biggest challenges faced by those researching how the condition affects the body. Many systems can be affected, but patients often have divergent symptoms and medical histories. That’s why Oh’s team used a multi-cohort design that recruited 74 patients who had lived with ME/CFS for less than 4 years and 75 who had been diagnosed more than 10 years ago. “Understanding and separating early vs. long-term disease ended up being a critical differentiator, as microbial and metabolic traits – or biomarkers – differed between short vs. long-term disease,” Oh told Technology Networks. Oh and colleagues used a technique called shotgun metagenomics to compare microbiome and plasma samples from these two groups against a control group of 79 people without ME/CFS. They also recorded clinical and lifestyle surveys from their cohorts.

The team found clear and significant differences between the patient groups. “The short-term group had the greatest microbial dysbiosis,” Oh said. In these patients, microbes that produce certain metabolites were “largely absent”. This includes those involved in the production of tryptophan, butyrate and propionic acid. These substances are important for regulating metabolic and endocrine functions, including modulating inflammatory responses,” Oh noted.

The evolution of ME/CFS

The picture in the long-term cohort was different. These patients, Oh noted, “had returned to a state closer to that of the controls, showing more normal microbial diversity with the reacquisition of some low abundance species.” Nevertheless, the longer-term ME/CFS patients reported a greater number of disease-associated symptoms, such as fibromyalgia and sleep problems.

The longer-term patients also showed changes at a cellular and molecular level. This cohort had metabolic alterations within their blood plasma that were absent in the short-term cohort. Some of these changes were linked to the immune system and the patients also showed altered levels of immune cells compared to controls.

Oh said that these differences were surprising, but have allowed her team to build a hypothesis of how ME/CFS evolves over time. “The microbial dysbiosis seen in short-term patients may have cumulative and long-term effects, where damage may be caused by an initial trigger, resulting in cascading events. We conjectured that ME/CFS progression may begin with loss of beneficial microbes, particularly short-chain fatty acid [SCFAs; important bacterial metabolites] producers, resulting in more pervasive gastrointestinal phenotypes that are later reflected in plasma metabolite levels.” The study’s design means that the findings are correlational, rather than causative. But such initial data is required to then test the team’s hypothesis in further experiments.  

In a press release linked to the study, Oh noted that she plans future research to further stratify patients by disease features, such as inflammatory bowel disease. This initial data can hopefully help researchers come closer to understanding this complex and stubborn disease.

Professor Julia Oh was speaking to Ruairi J Mackenzie, Senior Science Writer for Technology Networks. 

Reference: Xiong R, Gunter C, Fleming E et al. Multi-‘omics of gut microbiome-host interactions in short- and long-term myalgic encephalomyelitis/ chronic fatigue syndrome patients. Cell Host & Microbe. 2023. doi: 10.1016/j.chom.2023.01.004