Introduction

Myalgic encephalomyelitis (ME) may be been linked to changes in gut physiology and in particular, to alterations in the populations of microbes that reside within the gut called the microbiota. The microbiota is dominated by large populations of viruses, the majority of which target bacteria for infection and are called bacteripphages (phages). Phages can produce profound changes in bacterial populations by altering how they behave and function or by killing them. Ultimately this can result in the eradication of populations of “beneficial bacteria” in the gut leading to disease. Our study proposes to use powerful new DNA sequencing technologies and computer programs to identify populations of phages represented in faecal samples taken from patients with severe ME, and investigate whether these bacterial viruses have an impact on diseases.

The Team

The student will benefit from extensive knowledge and technical expertise of senior scientists in the groups of Professors Wileman and Carding at the UEA-Norwich Medical School. The project also benefits from collaborative work with Cornell University (USA), which is undertaking a parallel project with a USA cohort of ME patients.

Project Description

Myalgic encephalomyelitis (ME) is a multifactorial disorder affecting the nervous system characterised by severe and prolonged fatigue. The cause is unknown although alterations in the immune system, recurrent or persistent infections, that can originate in the gut, autoantibody production and the effectiveness of B cell-depletion therapy suggest that ME patients suffer from autoimmune responses.

This study aims to answer important questions concerning the role of the enteric phage/virome in CFS/ME. Specifically, can long-read sequencing identify new enteric phages, many of which may have been locked within the 'viral dark matter'? Do the phages populations differ between patients and controls? Can the phages identified reduce populations of 'beneficial bacteria' and/or affect the metabolism of the microbiota? Can phage DNA profiling be used in biomarker development for CFS/ME?

Indeed, patients with ME have altered immune signatures indicative of viral infection with most patients having persistent or intermittent symptoms of gastrointestinal dysfunction, with a significant subset presenting with chronic enterovirus infection of the stomach.

In contrast to acquired environmental virus infections, there is evidence that alterations in virus populations resident in the human gut (the gut virobiota) are linked to the development of inflammatory diseases.

This PhD project will investigate whether the underlying causes of ME are related to the presence of specific virus populations within the gut virobiota. Using high throughput DNA/RNA sequencing technology and bioinformatics tools we will determine if and how both resident gut bacteria and virus populations changes with disease progression and if a distinct virobiota signature can be identified in ME patients.

Funding

Funding is via Invest in ME Research and UEA.

References