Materials and methods for improving immune responses and skin and/or mucosal barrier functions

Inventors

Berkes, Eva A.Monsul, Nicholas T.BOEHM, Frederick T.

Assignees

Quorum Innovations Inc

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Publication Number

US-10004772-B2

Patent

Publication Date

2018-06-26

Expiration Date


Abstract

The subject invention provides compositions and methods for treating human dermatological conditions by employing a microbiome-centered treatment approach. Preferred embodiments of the invention provide pharmaceutical and cosmetic compositions, and the methods of using the same, comprising a strain of Lactobacillus fermentum bacterium, or bioactive extracts thereof, derived from human microbiota and capable of growing in biofilm phenotype.

Core Innovation

The document describes microbiome-centered dermatological and mucosal treatment that uses a human-derived biofilm-grown Lactobacillus fermentum strain with an Accession No. PTA-122195 (Lf Qi6) and preparations comprising bioactive biofilm extracts and biofilm-derived extracts/lysates. The invention addresses inhibition of pathogenic biofilm growth and adhesion and promotes detachment, while promoting commensal biofilm growth, including modulation involving Staphylococcus epidermidis.

The disclosed approach is linked to improvements associated with skin barrier dysfunction and innate immune dysfunction. The document reports upregulation of the skin barrier protein filaggrin and innate immune peptides including human beta defensins, HβD-2 and HβD-3, and LL-37 (cathelicidin), together with modulation of inflammatory cytokines such as IL-1α, IL-4, IL-13, and TSLP.

A mechanistic connection is stated through biofilm-derived bioactives acting as PPAR agonists, including PPAR-alpha, PPAR-beta/delta, and PPAR-gamma, with associated changes in PPAR expression. The summary also describes microbiological and cell and ex vivo skin evidence including effects against methicillin-resistant Staphylococcus aureus (MRSA) versus commensal modulation, with claimed outcomes including anti-biofilm inhibition, anti-adhesion, detachment, and filaggrin RNA/protein upregulation and increased beta-defensins.

Claims Coverage

The independent claim covers applying a microbial growth-inhibiting amount of a preparation containing a specific biofilm-grown Lactobacillus fermentum strain (Accession No. PTA-122195) to inhibit microbial growth on a surface or in a composition. The dependent claims refine the inventive coverage by specifying particular surfaces, functional outcomes on skin barrier function, specific biological activity via PPAR agonism, and particular microbial targets such as MRSA, as well as a preparation property that the preparation is edible.

Biofilm-grown Lactobacillus fermentum preparation for microbial growth inhibition

Applying to the surface or composition a microbial growth-inhibiting amount of a preparation comprising a bioactive Lactobacillus fermentum strain having Accession No. PTA-122195 grown as a biofilm.

Skin surface treatment

The method is performed on a surface that is skin.

Enhancing skin barrier function

Using the preparation to enhance skin barrier function.

PPAR agonist activity

Using the preparation as an agonist of PPAR.

MRSA growth inhibition

Inhibiting the growth of methicillin-resistant Staphylococcus aureus (MRSA).

Edible preparation

The preparation produced is edible.

Across the claim set, the core coverage is a method of inhibiting microbial growth by applying a microbial growth-inhibiting amount of a preparation comprising a specific biofilm-grown Lactobacillus fermentum strain (Accession No. PTA-122195). Dependent coverage specifies use on skin, enhancement of skin barrier function, PPAR agonist activity, inhibition of MRSA growth, and that the preparation is edible.

Stated Advantages

Inhibits microbial growth by inhibiting pathogenic biofilm growth and adhesion while promoting detachment.

Promotes commensal biofilm growth, including modulation involving Staphylococcus epidermidis.

Enhances skin barrier function through upregulation of filaggrin.

Improves innate immune function through increased human beta defensins and LL-37 (cathelicidin).

Modulates inflammatory cytokines including IL-1α, IL-4, IL-13, and TSLP.

Provides a mechanistic link via PPAR agonism (PPAR-alpha, PPAR-beta/delta, PPAR-gamma) associated with PPAR expression changes.

Documented Applications

Dermatological and mucosal treatment using topical pharmaceutical/cosmetic compositions comprising the biofilm-grown Lactobacillus fermentum preparation and bioactive biofilm extracts/lysates.

Use in methods for inhibiting microbial growth on a skin surface and to inhibit MRSA growth.

Oral mucoadhesive gel concepts for eosinophilic GI disease, with optional steroid described as budesonide, including mucoadhesive oral gel.

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