Skip to main content Skip to secondary navigation

Gowri Subedar

Main content start

“Modeling 'Gut-Skin' Axis in the Immunopathogenesis of Psoriasis”

Advised by Prof. Michaëlle N. Mayalu

Abstract: The gut-skin axis is the proposed bidirectional communication between the gut and skin. Disturbances along this axis may result in skin pathologies that manifest as gut comorbidities. Psoriasis, a prevalent and chronic autoimmune skin disorder, is characterized by disruptions in this axis. Patients exhibit variations in the abundance and composition of the skin and gut microbiota, leading to changes in plasma metabolite and neurotransmitter concentrations. Additionally, genetic factors contribute to a positive feedback loop involving cell proliferation and a sustained immune response.

Existing quantitative studies of psoriasis primarily focus on modeling keratinocyte-dendritic cell-T-cell interactions, overlooking the impact of other immune cells and interactions with the gut and skin microbiota. Moreover, these models lack interpretability, making it challenging to translate findings to aid with clinical decision-making. We aim to develop a comprehensive and interpretable mathematical framework of the gut-skin axis, encompassing bacterial, immune, and skin cell interactions at the system level. Our objective is to demonstrate how these interactions can constrain the system, giving rise to system multistability. This exploration will further shed light on the conditions under which healthy and diseased phenotypic states manifest.

We envision our study as an initial step toward creating more sophisticated parametric mathematical models of psoriasis. These models, characterized by microbiome dynamics, can offer deeper insights into fundamental principles that drive psoriasis pathogenesis. Furthermore, our research aims to identify potential therapeutic targets and predict the efficacy of different treatments for individuals, contributing to a more personalized approach to psoriasis treatment.