Establishing the role of low level systemic pathogens in Chronic disease

It is becoming clear that the human microbiome extends beyond the gut with bacteria and fungi found in our cells and tissues. In a range of chronic diseases, evidence is emerging that combinations of pathogens are involved in disease.  Myalgic Encephalomyelitis/Chronic fatigue (ME/CFS), Chronic Lyme disease (CLD) and PANS/PANDAS have been linked to the presence of currently unknown pathogens. In CLD and PANS/PANDAS patients antibiotic treatments have been shown to improve symptoms. In ME/CFS raised levels of anti-microbial peptides, increased gut permeability and elevated levels of antibodies raised against specific bacteria have been found in blood. Data from our collaborator SoftCell biologicals indicates that high levels of wall less bacteria (L-Forms) can be cultured from blood, with high numbers of pathogens also detected by deep sequencing.

In this project we will examine blood samples of PANS/PANDAS, ME/CFS, CLD and healthy controls using metagenomic sequencing approaches. L-Form cultures will be established and subjected to anti-pathogen agents. Cell lines will be infected with L-Form organisms and thoroughly characterised using Raman microscopy and assays of mitochondrial function/dynamics. Oxford studies have shown that peripheral blood mononuclear cells from individuals with ME/CFS, multiple sclerosis and healthy controls are very different. Mitochondria also directly interact with parasites. Anti-pathogen agents and drugs which modulate mitophagy will be tested to determine if they can enhance the clearance of pathogens. The impact of Oxidative phosphorylation, glycolysis and different fuels on mitochondrial pathogen clearance will be investigated.