Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease characterized by intense and debilitating fatigue not due to physical activity that has persisted for at least 6 months, post-exertional malaise, unrefreshing sleep, and accompanied by a number of secondary symptoms, including sore throat, memory and concentration impairment, headache, and muscle/joint pain. In patients with post-exertional malaise, significant worsening of symptoms occurs following physical exertion and exercise challenge serves as a useful method for identifying biomarkers for exertion intolerance. Evidence suggests that intestinal dysbiosis and systemic responses to gut microorganisms may play a role in the symptomology of ME/CFS. As such, we hypothesized that post-exertion worsening of ME/CFS symptoms could be due to increased bacterial translocation from the intestine into the systemic circulation. To test this hypothesis, we collected symptom reports and blood and stool samples from ten clinically characterized ME/CFS patients and ten matched healthy controls before and 15 minutes, 48 hours, and 72 hours after a maximal exercise challenge. Microbiomes of blood and stool samples were examined. Stool sample microbiomes differed between ME/CFS patients and healthy controls in the abundance of several major bacterial phyla. Following maximal exercise challenge, there was an increase in relative abundance of 6 of the 9 major bacterial phyla/genera in ME/CFS patients from baseline to 72 hours post-exercise compared to only 2 of the 9 phyla/genera in controls (p = 0.005). There was also a significant difference in clearance of specific bacterial phyla from blood following exercise with high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS patients versus clearance in the controls. These results provide evidence for a systemic effect of an altered gut microbiome in ME/CFS patients compared to controls. Upon exercise challenge, there were significant changes in the abundance of major bacterial phyla in the gut in ME/CFS patients not observed in healthy controls. In addition, compared to controls clearance of bacteria from the blood was delayed in ME/CFS patients following exercise. These findings suggest a role for an altered gut microbiome and increased bacterial translocation following exercise in ME/CFS patients that may account for the profound post-exertional malaise experienced by ME/CFS patients.
Highlights
The Centers for Disease Control estimates that between 836,000 and 2.5 million people in the U.S suffer from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [1], resulting in substantial disability [2] and significant socio-economic impact [3,4]
Compared to controls clearance of bacteria from the blood was delayed in ME/CFS patients following exercise. These findings suggest a role for an altered gut microbiome and increased bacterial translocation following exercise in ME/CFS patients that may account for the profound post-exertional malaise experienced by ME/CFS patients
The results presented here add further to the previous findings suggesting that ME/CFS patients have an altered gut microbiome and further suggest that increased bacterial translocation following exercise provides a potential explanation for the profound post-exertional malaise experienced by some ME/CFS patients
Summary
The Centers for Disease Control estimates that between 836,000 and 2.5 million people in the U.S suffer from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [1], resulting in substantial disability [2] and significant socio-economic impact [3,4]. One current model of disease suggests that a trigger event (e.g. infection) results in a chronic inflammatory state characterized by increased proinflammatory cytokine production, increased reactive oxygen and nitrogen species, altered intracellular signaling, increased intestinal permeability and systemic activation of innate immune receptors, altered glutaminergic and dopaminergic neurotransmission, mitochondrial dysfunction, and aberrant autoimmune responses [6,7,8,9,10,11] These pathogenic processes appear to be self-sustaining and self-amplifying and account for the characteristic symptoms of ME/CFS and other systemic disorders characterized by central and peripheral fatigue [5,9]. Subgroups based on the presence or absence of gastrointestinal symptoms [14] and post-exertional malaise [15] has been described
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