Effects of Altered Skin Microbiota and Host Skin Immunity on Risks for Staphylococcus aureus Colonization and Infection

Asymptomatic staphylococcal colonization has been identified as one of the modifiable risk factors for Staphylococcus aureus (S. aureus) infections. Previous studies have shown that short-term decolonization is effective for preventing infections in surgical patients and in patients who were admitted to the intensive care unit (ICU). However, concerns for the increasing prevalence of antibiotic resistant bacteria has prevented the universal application of topical or broad-spectrum antibiotics to achieve long-term decolonization.Accumulating literature suggests that hostcommensal interactions may modulate host immune responses to pathogens. A better understanding of these host-microbe cross-talks may provide insights on novel bacterial interfering approaches to decolonizing pathogens such as S. aureus. Longitudinal changes in the skin microbiota and in the skin innate immune response may also provide valuable prognostic information about patients’ response to therapy and prognosis. Natural history studies on patients with chronic inflammatory skin diseases can provide an optimal opportunity to observe how the host and microbes interact under natural experiment conditions. For example, currently available therapeutic agents for psoriasis fall into two major categories of immune-modulating agents- targeted vs. non-targeted. However, little is known about the shortand long- term effects of individual therapeutic agents on the host’s risk for Staphylococcus aureus colonization or infection. There has been no comprehensive accounts on the temporal dynamics in shaping or re-modeling the skin microbiota through changes in the skin immunity during and after a treatment course. In particular, it is unknown whether the skin microbiota restores to its beforetreatment or before-flare status; if yes, whether the duration for recovery is correlated with the time interval between relapses. To this end, we propose the following Specific Aims in the current proposal: Aim #1. To estimate risks for S. aureus colonization and infection among psoriasis patients who received topical or oral monotherapies targeting various components of the skin immunity in a prospective cohort study Aim #2. To determine the strength of associations between changes in the host skin immunity and risks for staphylococcal decolonization as well as the mediating role of an altered skin microbial profile in response to therapeutic perturbations by conducting a nested case-control study Aim #3. To examine the prognostic performance of alterations in the skin microbiota and in the skin immunity on clinical outcomes: (1) staphylococcal colonization status; (2) lack of significant improvement in the disease severity using classic (cumulative) case-control analysis

Project ID:PC10404-0019
External Project ID:MOST104-2314-B182-002