Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness of unknown underlying mechanisms and without an accepted therapy. According to Fukuda diagnostic criteria, primary symptoms reported by patients are fatigue, muscle and/or joint paint, sore throat, headaches, unrefreshing sleep, and post-exertional malaise. Individuals diagnosed with ME/CFS often report gastrointestinal symptoms such as constipation, diarrhoea, and intestinal discomfort that are part of other conditions such as irritable bowel syndrome. The role of gut microbiota in ME/CFS patients is still poorly understood.
A recent study, led by Prof. Maureen Hanson from the Department of Molecular Biology and Genetics at Cornell University in Ithaca, NY, USA, has found that ME/CFS patients have an altered composition of the gut microbiota that may play a role in increased microbial translocation and inflammatory symptoms in this condition.
The researchers performed a gut microbiota analysis of stool from ME/CFS patients (n=48) and healthy controls (n=39). Inflammatory markers including C-reactive protein (CRP), intestinal fatty acid-binding protein (I-FABP), lipopolysaccharide (LPS), LPS-binding protein (LBP) and soluble CD14 (sCD14) were also measured from serum samples. The gut epithelium is an efficient barrier that prevents absorption of LPS derived from Gram-negative gut microbiota. Increased LPS levels in the bloodstream resulting from chronic LPS stimulation in vivo are transported by lipoproteins and LBP, which is a plasma protein produced by gastrointestinal and hepatic epithelial cells that increases the binding of LPS to CD14, thus contributing to LPS translocation into the circulation.
ME/CFS patients had significantly higher plasma levels of the microbial translocation markers LPS, LBP and sCD14 than healthy individuals. Levels of LBP correlated with LPS and sCD14, while LPS levels correlated with sCD14. Increased plasma levels of markers of microbial translocation may be involved in inflammatory symptoms of ME/CFS.
Faecal microbiota of ME/CFS patients exhibited reduced diversity and different composition from healthy controls. In particular, ME/CFS samples showed a reduction in the relative abundance and diversity of members belonging to the Firmicutes phylum and higher relative abundance of Proteobacteria. Furthermore, those with ME/CFS had fewer bacterial species known to be anti-inflammatory-for example, those in the genera Faecalibacterium and Bifidobacterium-and increased specific species often reported to be pro-inflammatory-bacteria belonging to the Proteobacteria phylum. Similar observations have also been reported in inflammatory bowel disease patients.
Diagnosis of this condition usually requires lengthy tests administered by an expert physician. According to these novel findings, study of the gut microbiota from stool samples and plasma microbial translocation markers may in the future offer a non-invasive diagnosis of the disease.
“In the future, we could see [the study of stool and blood samples] as a complement to other non-invasive diagnoses, but if we have a better idea of what is going on with these gut microbes and patients, maybe clinicians could consider changing diets, using prebiotics such as dietary fibres or probiotics to help treat the disease”, said Ludovic Giloteaux, a postdoctoral researcher and first author of the study.
To sum up, ME/CFS patients have an altered composition of gut microbiota and increased microbial translocation, as shown by increased plasma levels of microbial translocation markers. Although it is still unknown whether the gut dysbiosis is a cause or a consequence of disease, further research on the gut environment of these patients might improve ME/CFS diagnosis.
Giloteaux L, Goodrich JK, Walters WA, Levine SM, Ley RE, Hanson MR. Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome. Microbiome. 2016; 4(1):30. doi:10.1186/s40168-016-0171-4.