Harnessing postbiotics to target intracellular pathogens in hidradenitis suppurativa

Active Project Grant Awarded Last action

Award ID
F30AI202839
Recipient
Awarding agency
Obligated
$55,114

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 0% complete
Place of performance
Miami, FL 33136, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by painful skin lesions with an immense morbidity burden. HS afflicts 1 to 4% of americans. There is no cure, and even with new treatment advances, about half of the individuals living with HS experience relapse. Unfortunately, the lack of knowledge regarding the cause of HS and the origins of chronic skin inflammation impedes effective therapies. Microbial dysbiosis is a major hallmark of HS and consists of a shift from benign commensal bacteria to gram- negative anaerobic pathogens. Our group previously identified that chronic skin conditions with unresolved inflammation can harbor intracellular pathogenic bacteria that active immune signaling and destroy the skin barrier. Additionally, we discovered that applying non-viable commensal lactobacilli bacteria (lactobacilli postbiotic therapy, LPT) kills intracellular methicillin-resistant staphylococcus aureus (MRSA) and strengthens the skin barrier. We used rnaseq analysis of HS tissue samples (N=22) to determine significant dysregulation of two immune processes that may be modulated by intracellular bacteria to support chronic HS inflammation: the inflammasome pathway and epidermal barrier functions. Like in chronic inflammatory skin conditions, we hypothesized that LPT will reduce intracellular bacteria, suppressing inflammasome activity and restoring barrier functions. Thus, the goal of this proposal is to evaluate the protective and therapeutic effects of LPT, against intracellular bacteria isolates from HS (aim 1), and epidermal barrier functions in HS (aim 2). We will use a patient-centered approach including an existing biobank of HS tissue, cells, and bacterial isolates, a 3D organotypic HS model, and a human skin EX vivo infection model. This will enable the first study of LPT for intracellular pathogens for the prevention and treatment of HS. Treatment with non-viable lactobacilli may represent a broadly-applicable approach to target the microbiome in other dysbiosis-associated immunologic diseases. This fellowship proposal provides a tailored training opportunity in precision medicine, integrative skin microbiology, human models of skin disease, and bridging discovery to therapy towards career development as a physician-scientist in the immunodermatology field.

Quick answers

Who received award F30AI202839?

F30AI202839 was awarded to University Of Miami by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on February 19, 2027.

How much is award F30AI202839 worth?

$55,114 has been obligated on F30AI202839.

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