A role for a leaky gut and the intestinal microbiota in the pathophysiology of ME/CFS Vipond 2019 PhD thesis

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This research was funded or part funded by Invest in ME research

https://ueaeprints.uea.ac.uk/70522/

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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Abstract

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 13:02
Last Modified: 09 Apr 2019 13:02
URI: https://ueaeprints.uea.ac.uk/id/eprint/70522
DOI:
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I want transcriptome data from the gut of patients in PEM, to look at proteins involved with instestinal barrier function. It's not just bacteria that can affect this. And from my own experience when I've been very ill and had other cook for me (if I managed to eat) the diet has not always been gut microbiome friendly to say the least.. I haven't got the energy to read through this now (ironicly reading about leaky gut, diet and IBD for work), but how do they take this into account?
 
Interesting, the concepts of a leaky gut and disordered gut bacteria used to be laughed at by allopathic medicine. Or, at least cause eye rolling. Now, this topic is getting more and more attention. Thank goodness!

Just my own experiences, but there does seem to be a correlation between an increase in GI issues, and brain fog. When my GI problems/pain flare, the brain fog worsens. Too much fibre or carbs, can both cause GI problems to increase, which after experiencing this hundreds if not thousands of times over the decades, appears to lead directly to increased brain fog.

During gradual onset, my IBS became much more painful.

ETA: just added a bit more info.
 
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DokaGirl said:
Interesting, the concepts of a leaky gut and disordered gut bacteria used to be laughed at by allopathic medicine. Or, at least cause eye rolling. Now, this topic is getting more and more attention. Thank goodness!

Just my own experiences, but there does seem to be a correlation between an increase in GI issues, and brain fog. When my GI problems/pain flare, the brain fog worsens. Too much fibre or carbs, can both cause GI problems to increase, which after experiencing this hundreds if not thousands of times over the decades, appears to lead directly to increased brain fog.

During gradual onset, my IBS became much more painful.

ETA: just added a bit more info.
Click to expand...
There might be correlations between "leaky gut" and a more leaky blood-brain-barrier, that could perhaps cause brain-fog?
 
@MeSci and @Andy
Just got an email from Daniel V thanking us for pointing this out. He is contacting the UAE library to correct this and also going to have a read thro' the rest to check, now that he has a bit more time.

Simon Carding's talk at IiMER covered his PhD. Hopefully, that will be out soon, as the Anne Ortegren memorial lecture is now on Youtube, hopefully the rest will follow.

Daniel also said:

"Part of this work, however, has been submitted for publication based on faecal metabolomics data and a targeted mass-spec analysis of bile acids. I hope this will be available soon. "
 
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