A role for a leaky gut and the intestinal microbiota in the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Vipond, Daniel (2018) A role for a leaky gut and the intestinal microbiota in the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Doctoral thesis, University of East Anglia.

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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.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Jackie Webb
Date Deposited: 09 Apr 2019 12:02
Last Modified: 30 Apr 2020 00:39
URI: https://ueaeprints.uea.ac.uk/id/eprint/70522

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