The role of the gut microbiome in psoriatic arthritis pathophysiology, a phenomic study

Abstract

Abstract: Background: Psoriasis is a chronic inflammatory disease of the skin affecting 2-3% of UK population. 30% of people affected by psoriasis will develop a progressive form of arthritis within 10 years of the skin condition onset. Psoriatic arthritis (PsA, is well described now as a systemic disease in which delayed diagnosis and treatment can cause irreversible joint damage, disability, and a long range of comorbidities such as obesity, hyperlipidemia, etc. There is limiting but convincing evidence linking the gut microbiota to PsA in humans. Methods: Microbiome in Psoriatic ARThritis (MiPART) is a multicentre, prospective, observational study. MiPART collected and analysed stool, plasma, serum, and urine samples from PsA patients, ankylosing spondyloarthritis (AS) patients and healthy volunteers (HV). Analysis included metataxonomic, Nuclear Magnetic Resonance (NMR), metagenomics and multi omics integration of the data. Results: PsA presented a different gut microbiota profile when compared with AS and HV groups; this trend was observed at the alpha and beta community diversity levels of the metataxonomic and metagenomic data. PsA participants presented a lower alpha-diversity than HV and AS groups (Shannon index, p value = 0.011). Beta-diversity analysis also reported a clear split between PsA participants and HV and AS groups (Aitchison distance, p value = 0.012). Lipoprotein dysregulation was found in the serum samples, with an increase of IDL particles with respect to Apo-B100 concentration (p value = 0.020) such as cholesterol (p value = 0.020) in PsA samples when compared to AS and HV ones. Finally, a network of PsA signatures was established with a supervised multi omics analysis. Discussion: The novel results presented here suggest a more extensive than previously recognised link between PsA and the gut microbiome. These results come with limitations, which require further integration of the pending experiments and future in vitro work for proper validation. However, the scope of the data presented in this thesis is a promising step to continue investigating the associations between the gut microbiota and PsA or other extraintestinal chronic autoimmune diseases.