Investigating the Human Gut Virome in ME/CFS Patients and the Impact of Faecal Microbiota Transplantation

Haagmans, Rik (2024) Investigating the Human Gut Virome in ME/CFS Patients and the Impact of Faecal Microbiota Transplantation. Doctoral thesis, University of East Anglia.

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Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease characterised by chronic fatigue resulting from emotional, physical or mental exertion. Its cause is unknown and there is no cure. Viral infections are commonly associated with ME/CFS onset and most patients have gastrointestinal (GI) disturbances, with GI microbial dysbiosis being highly associated with disease. Microbiota replacement therapy (faecal microbiota transplantation, FMT) is a promising treatment option. However, while the GI virome plays a significant role in GI microbiome homeostasis and in health, it’s role in ME/CFS and the effect of FMT are unclear. This thesis project aimed to investigate this through a metagenomic and TaqMan array card-based analysis of the GI virome of participants in a Phase II placebo-controlled clinical trial, the Comeback Study (NCT03691987), investigating safety, acceptability and efficacy of FMT in 80 mild to severe ME/CFS patients.

First, to determine bias and reproducibility of the viral metagenomics methods, an epifluorescence microscopy method was optimised, and an image analysis workflow was developed. This enabled the reproducible quantification of single stranded and double stranded RNA and DNA prokaryotic and eukaryotic viruses and production of a mock virus community.

Next, the mock virus community was used to spike faecal samples to assess methodological biases and reproducibility, comparing a whole transcriptome amplification kit (WTA2) and sequence-independent single primer amplification (SISPA). This showed that assemblies ofWTA2 libraries had higher contiguity and diversity, whereas SISPA gave more consistent abundance estimates.

Finally, TaqMan analysis of the Comeback Study showed no indication of increased prevalence of GI pathogens in ME/CFS. However, viral metagenomics showed that FMT increased virus diversity in recipients virome, with donor viruses persisting and with virome similarity to the donor increasing, with distinct levels of engraftment between donors . This suggests that FMT produces a healthier virome in ME/CF patients, depending on the donor.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User:	Chris White
Date Deposited:	13 Mar 2025 09:19
Last Modified:	13 Mar 2025 09:19
URI:	https://ueaeprints.uea.ac.uk/id/eprint/98740
DOI:

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