Probiotic compositions containing clostridiales for inhibiting inflammation

Inventors

Berry, DavidKaplan, JohanneRahman, Shaila

Assignees

PharmaBiome AGFlagship Pioneering Inc

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Publication Number

US-11607432-B2

Patent

Publication Date

2023-03-21

Expiration Date


Abstract

Pharmaceutical compositions containing microbial entities are described herein. The pharmaceutical compositions may optionally contain or be used in conjunction with one or more prebiotics. Uses of the pharmaceutical compositions to treat or prevent disorders of the local or systemic microbiome in a subject are also provided.

Core Innovation

The patent describes a method of treating dysbiosis in a subject by administering a pharmaceutical composition comprising a bacterial population of a single bacterial species, wherein the species is Enterococcus gallinarum. The disclosed approach is framed around microbiome changes associated with dysbiosis and the use of a defined bacterial species population for treatment.

The patent further describes probiotic/pharmaceutical compositions that contain a bacterial population of non-pathogenic bacterial cells with anti-inflammatory activity. The bacterial populations include anti-inflammatory bacterial populations from the order Clostridiales, including genera such as Blautia, Clostridium, Eubacterium, and Ruminococcus, and members of the family Lachnospiraceae.

The compositions are intended to modulate host immunity by affecting immune signaling and cellular immune responses. This immune modulation is characterized by decreasing pro-inflammatory cytokine secretion and/or increasing anti-inflammatory cytokines by human peripheral blood mononuclear cells, with T-cell subset shifts including Treg/Th17/Th1/Th2 used as immune readouts associated with the compositions.

Claims Coverage

The provided independent claim is directed to treating dysbiosis by administering a pharmaceutical composition containing a bacterial population of a single bacterial species. The main inventive features are the specific bacterial species Enterococcus gallinarum and the functional requirement to treat dysbiosis in the subject upon administration.

Single-species Enterococcus gallinarum pharmaceutical composition for treating dysbiosis

A method of treating dysbiosis in a subject in need thereof by administering to the subject a pharmaceutical composition comprising a bacterial population of a single bacterial species, wherein said species is Enterococcus gallinarum, such that dysbiosis in the subject is treated.

Human subject

The method of treating dysbiosis is applied to a human subject.

Lyophilized bacterial population

The pharmaceutical composition includes a lyophilized bacterial population.

Oral administration

Administering the pharmaceutical composition orally.

Pro-inflammatory cytokine selection

The pro-inflammatory cytokine is selected from IL-1a, IL-1b, IL6, IFN gamma, and TNF alpha.

Directional T-cell subset change

The treatment decreases the proportion of Th2 cells in the subject.

Overall, the claim coverage centers on administering a single-species bacterial population of Enterococcus gallinarum in a pharmaceutical composition to treat dysbiosis, with dependent claims further refining subject type, formulation/processing, oral delivery, and immunological characterization involving selected cytokines and decreased Th2-cell proportion.

Stated Advantages

Decreases pro-inflammatory cytokine secretion by human PBMCs.

Increases anti-inflammatory cytokines by human PBMCs.

Reduces inflammation at gastrointestinal and distal sites, including placenta, spleen, skin, liver, uterus, blood, eye, mouth, ear, nose, lung, pancreas, brain, embryonic sac, and vagina.

Documented Applications

Treating dysbiosis in a subject in need thereof by administering the disclosed pharmaceutical composition.

Inflammation reduction at gastrointestinal and distal sites, including placenta, spleen, skin, liver, uterus, blood, eye/conjunctiva, mouth, ear, nose, lung, pancreas, brain, embryonic sac, and vagina.

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