Compositions and methods for transplantation of colon microbiota
Inventors
Sadowsky, Michael J. • Khoruts, Alexander • Weingarden, Alexa R. • Hamilton, Matthew J.
Assignees
University of Minnesota System
Publication Number
US-12295974-B2
Publication Date
2025-05-13
Expiration Date
2032-03-09
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Abstract
The present invention provides compositions that include an extract of human feces, and methods for using such compositions, including methods for replacing or supplementing or modifying a subject's colon microbiota, and methods for treating a disease, pathological condition, and/or iatrogenic condition of the colon.
Core Innovation
The invention provides compositions that comprise an extract or preparation of human feces, particularly focusing on a composition that contains non-pathogenic fecal bacteria, and methods for their use. These compositions are produced by standardized processing from the stool of rigorously screened human donors, unrelated to the recipient. The compositions optionally contain a small proportion of non-living material (no greater than 10% by weight relative to biological material), may include a cryoprotectant such as glycerol, and can be formulated for various routes of administration, including rectal and oral delivery.
The problem addressed by the invention is the limited practical and aesthetic accessibility of fecal microbiota transplantation (FMT) as a treatment for recurrent Clostridium difficile infection (CDI). Existing FMT practices face barriers including lack of standardized donor screening, difficulties in donor material preparation and administration, and challenges with material acceptability due to odor and appearance. The described invention overcomes these barriers by providing nearly odorless, concentrated, and ready-to-use compositions suitable for clinical application, along with scalable methods for donor screening and material banking.
The standardized processing includes blending donor fecal material, sieving through a series of decreasing pore-size filters (down to 0.25 mm or smaller), and subsequent isolation of the biological material primarily containing viable gut bacteria, particularly members of the Firmicutes phylum. The composition is then combined with saline and a cryoprotectant and may be used fresh or stored frozen for later use. The invention further provides for the administration of these compositions to treat, prevent, or ameliorate diseases or conditions of the colon that are associated with a dysfunctional or pathological composition of the colon microbiota, and specifically treats or prevents recurrent CDI by increasing the abundance of beneficial bacteria.
Claims Coverage
The patent contains one independent claim and several dependent claims, with the independent claim covering the primary inventive features.
Standardized fecal microbiota composition from an unrelated, rigorously screened donor
A method of treating or preventing recurrent Clostridium difficile infection (CDI) that uses a pharmaceutical composition derived from a fecal microbiota supply bank with a plurality of fecal preparations. - Each fecal preparation is obtained from a healthy, screened human donor who is unrelated to the recipient, excluding pathogenic materials by donor selection and laboratory screening. - The composition comprises non-pathogenic fecal bacteria extracted using standardized processes, ensuring consistency and safety.
Specified pharmaceutical composition including saline, a cryoprotectant, and non-pathogenic fecal bacteria
The composition is comprised of saline, a cryoprotectant (such as glycerol), and a single fecal preparation from the supply bank. - The non-pathogenic fecal bacteria include bacteria of the phylum Firmicutes, and may also encompass members of Bacteroidetes (as delineated in dependent claims). - The preparation and storage allow for materials to be banked and available when needed.
Rectal administration to increase Firmicutes abundance by clinically meaningful amounts
The method involves rectally administering the pharmaceutical composition to the subject. - This administration results in an increase in the relative abundance of one or more members of the phylum Firmicutes in the intestine of the subject by at least 5% compared to pre-treatment levels. - Measurement of the increase can be determined at 3, 10, 15, or 25 days after administration.
In summary, the independent claim is directed to a standardized, banked, and screened fecal microbiota composition (including Firmicutes and a cryoprotectant) for rectal administration from unrelated donors, designed to increase the beneficial intestinal bacteria and treat or prevent recurrent Clostridium difficile infection.
Stated Advantages
The compositions are nearly odorless, making them more aesthetically acceptable and easier to handle in clinical settings.
Standardized processing and rigorous donor screening increase safety and reliability by reducing pathogen transmission risks.
Banked, frozen preparations enable timely availability of material without the need for immediate donor identification, improving practicality and access.
Concentrated and filtered compositions simplify administration and reduce technical difficulties during procedures.
Use of these compositions has a high success rate in clearing recurrent Clostridium difficile infections, including in patients with inflammatory bowel disease.
Documented Applications
Treatment or prevention of recurrent Clostridium difficile infection in patients who have failed standard antibiotic therapies.
Replacement, supplementation, or modification of a subject's colon microbiota to restore normal microbial community structure.
Treatment of diseases or pathological conditions of the colon characterized by a dysfunctional or pathological microbiota composition, including autoimmune colitis, infectious colitis, and colitis caused by Shigella or E. coli.
Treatment of patients with underlying inflammatory bowel disease, ulcerative colitis, Crohn's disease, irritable bowel syndrome, chronic diarrhea, or chronic constipation.
Use in prophylactic therapy for subjects at risk for developing colon diseases associated with microbiota dysfunction.
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