Methods of decreasing dysbiosis and restoring a microbiome
Inventors
Norman, Jason • Olle, Bernat • Roberts, Bruce • Menon, Rajita
Assignees
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Publication Number
US-12161680-B2
Publication Date
2024-12-10
Expiration Date
Abstract
Provided herein are methods for decreasing dysbiosis, restoring the microbiome, and/or increasing recovery of a healthy microbiome (e.g. following a dysbiosis inducing event), by administering pharmaceutical compositions to a subject. Also provided are methods for protecting the microbiome of a subject and/or colonizing the microbiome of a subject by administering pharmaceutical compositions to the subject.
Core Innovation
The invention relates to treating or preventing Clostridium difficile infection in a subject by administering vancomycin and, in addition, administering a therapeutically effective amount of a pharmaceutical composition comprising a purified bacterial mixture. The purified bacterial mixture comprises multiple bacterial strains defined by 16S rDNA sequence identity to specified SEQ ID NOs.
The method includes vancomycin administered in multiple doses prior to administering the pharmaceutical composition. The pharmaceutical composition is also administered in multiple doses, and the total administered bacteria dose meets defined CFU thresholds, including at least 4.0×10^10 CFUs or 1.1×10^11 CFUs of bacteria.
The disclosure is directed to microbiome restoration and microbiome protection after dysbiosis, including microbiome colonization or recolonization, microbiome composition shifts, and assessment of colonization or engraftment by genomic markers. It also describes compositions and formulations containing purified bacterial strains, including spores or vegetative forms and lyophilized and/or spray-dried preparations.
Claims Coverage
The provided material identifies one independent claim. The claim covers a combined vancomycin and purified bacterial mixture regimen for treating or preventing Clostridium difficile infection, with the bacterial mixture defined by 16S rDNA sequence identity to specified SEQ ID NOs and administered with multiple-dose timing and minimum total CFU thresholds.
Combined vancomycin and purified bacterial mixture
A method for treating or preventing Clostridium difficile infection in a subject comprising administering vancomycin and administering, in addition, a therapeutically effective amount of a pharmaceutical composition comprising a purified bacterial mixture.
Bacterial mixture defined by 16S rDNA sequence identity to specified SEQ IDs
The purified bacterial mixture comprises bacterial strains comprising 16S rDNA sequence with at least 99% sequence identity to the nucleotide sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8.
Multiple-dose sequencing with defined total CFU thresholds
Vancomycin is administered in multiple doses prior to administering the pharmaceutical composition; the pharmaceutical composition is administered in multiple doses; and a total of at least 4.0×10^10 CFUs or 1.1×10^11 CFUs of bacteria are administered to the subject.
Claim coverage centers on combining vancomycin with a purified bacterial mixture, defining the mixture by 16S rDNA sequence identity to eight listed SEQ ID NOs, and requiring multiple-dose timing together with defined minimum total CFU thresholds.
Stated Advantages
Treating or preventing Clostridium difficile infection in a subject.
Microbiome restoration and microbiome protection after dysbiosis.
Targeting microbiome composition shifts and suppression of inflammation-associated microorganisms.
Monitoring engraftment or colonization durability over weeks to months.
Documented Applications
Treatment or prevention of Clostridium difficile infection in a subject.
Primary and recurrent Clostridioides/Clostridium difficile infection.
Colonizing or recolonizing the gut microbiome after dysbiosis.
Assessing colonization by sequencing, qPCR, and genomic marker approaches.
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