The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS).

Abstract

Myalgic encephalomyelitis (ME) or Chronic Fatigue Syndrome (CFS) is a neglected, debilitating multi-systemic disease without diagnostic marker or therapy. Despite  evidence for neurological, immunological, infectious, muscular and endocrine  pathophysiological abnormalities, the etiology and a clear pathophysiology  remains unclear. The gut microbiome gained much attention in the last decade with  manifold implications in health and disease. Here we review the current state of  knowledge on the interplay between ME/CFS and the microbiome, to identify  potential diagnostic or interventional approaches, and propose areas where  further research is needed. We iteratively selected and elaborated on key  theories about a correlation between microbiome state and ME/CFS pathology,  developing further hypotheses. Based on the literature we hypothesize that  antibiotic use throughout life favours an intestinal microbiota composition which  might be a risk factor for ME/CFS. Main proposed pathomechanisms include gut  dysbiosis, altered gut-brain axis activity, increased gut permeability with  concomitant bacterial translocation and reduced levels of short-chain-fatty  acids, D-lactic acidosis, an abnormal tryptophan metabolism and low activity of  the kynurenine pathway. We review options for microbiome manipulation in ME/CFS  patients including probiotic and dietary interventions as well as fecal  microbiota transplantations. Beyond increasing gut permeability and bacterial  translocation, specific dysbiosis may modify fermentation products, affecting  peripheral mitochondria. Considering the gut-brain axis we strongly suspect that  the microbiome may contribute to neurocognitive impairments of ME/CFS patients.  Further larger studies are needed, above all to clarify whether D-lactic acidosis  and early-life antibiotic use may be part of ME/CFS etiology and what role  changes in the tryptophan metabolism might play. An association between the gut  microbiome and the disease ME/CFS is plausible. As causality remains unclear, we  recommend longitudinal studies. Activity levels, bedridden hours and disease  progression should be compared to antibiotic exposure, drug intakes and  alterations in the composition of the microbiota. The therapeutic potential of  fecal microbiota transfer and of targeted dietary interventions should be  systematically evaluated.