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Title: A role for a leaky gut and the intestinal microbiota in the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
Author: Vipond, Daniel
ISNI:       0000 0004 7962 7243
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2018
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The field of ME/CFS research is challenged by many often confusing and conflicting reports of immune, neuroendocrine, autonomic, neurological dysfunction. During the prodromal phase of this condition patients often report flu-like symptoms, persistent chronic fatigue and gastro-intestinal symptoms including abdominal pain and discomfort. Its study is complicated by the lack of specific biomarkers and criteria to accurately define the illness, relying on the exclusion of other fatiguing illnesses. Recent publications suggest an altered intestinal microbiota and increased intestinal permeability are associated with ME/CFS. Further evidence is accumulating for dysfunctional energy, lipid and amino acid metabolism that may indicate oxidative stress and/or immune-mediated damage to mitochondria, disrupting the efficiency of aerobic respiration, explaining the effect of postexternal malaise (PEM), a unique characteristic for the diagnosis of ME. In this study, Next Generation Sequencing (NGS) and Nuclear Magnetic Resonance (NMR) spectroscopy probed the composition of the intestinal microbiota and faecal and serum microbiomes in 17 severe, house-bound patients and house-hold healthy controls (HHC). Severe, house-bound patients account for 0.5% of all ME/CFS research, yet it is estimated they represent 25% of the patient population. We found Faecalibacterium prausnitzii was significantly reduced in severe patients (p = 0.018) but did not replicate individual differences in faecal and serum metabolites that others have previously reported. We further enhanced a flow cytometry technique for detecting IgA coated bacteria in faecal suspensions and analysed the proportional differences between patients and HHCs. This demonstrated a trend for increased IgA-coated bacteria in most patients; however, this trend was reversed when repeated with a second sample produced a year on. Since the initial concept for this study, several advances have been made in sequencing methods and quality control standards for metagenomic and metabolomic studies. Based on these, we conclude further investigations are warranted using whole genome sequencing and targeted metabolomics to address the emerging hypotheses in ME/CFS research, with an emphasis on the study of severe, house-bound ME patients.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available