Compositions and methods for transplantation of colon microbiota
Inventors
Sadowsky, Michael J. • Khoruts, Alexander • Weingarden, Alexa R. • Hamilton, Matthew J.
Assignees
National Institutes of Health NIH • University of Minnesota System
Publication Number
US-9649343-B2
Publication Date
2017-05-16
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 comprising an extract or preparation of human feces containing living microbiota such as bacteria, eukaryotic cells, and viruses from the colon or intestines of a healthy human. These compositions have a highly enriched biological material content with substantially reduced non-living material. The materials are processed by filtering fecal samples through progressively smaller sieves, removing at least 91% of non-living material and resulting in particles that pass through specified sieve sizes, making the compositions odorless and suitable for pharmaceutical formulations, including oral administration.
The compositions are used in methods aimed at replacing, supplementing, or modifying a subject's colon microbiota to treat diseases or pathological and iatrogenic colon conditions such as Clostridium difficile colitis and other colitis types. The compositions can be administered via various routes including oral, rectal, or intubation methods, optionally following clearance of the subject's existing microbiota. The preparations may include cryoprotectants like glycerol for preservation and can be frozen for long-term storage without loss of efficacy.
The problem addressed arises from recurrent Clostridium difficile infection (CDI), a condition associated with disruption of normal gut microbiota primarily due to antibiotic use. Despite current antibiotic therapies, CDI recurrence remains high, especially due to destruction of protective gut bacteria. Fecal microbiota transplantation (FMT) has shown high success rates but its widespread use is limited by practical barriers like donor screening difficulties, preparation complexity, aesthetic concerns, lack of standardized materials, and limited availability. This invention solves these problems by providing standardized, odorless, highly enriched fecal compositions derived from rigorously screened donors and prepared by a filtration and concentration process, making FMT more accessible and acceptable.
Claims Coverage
The patent contains one independent claim directed to a method for preparing a substantially odorless oral human fecal pharmaceutical composition. The claims focus on the preparation process and the characteristics of the resulting composition.
Filtration through progressively smaller sieves to generate odorless fecal composition
The method comprises filtering a human fecal sample through multiple filter media with progressively smaller sieve sizes, where the smallest sieve size is equal to or less than 0.5 mm, to produce a filtrate that is a substantially odorless human fecal composition containing microbiota from the donor.
Use of smaller sieve sizes for filtration
The method includes embodiments where the smallest sieve size used for filtration is equal to or less than 0.25 mm, 0.15 mm, 0.075 mm, or 0.053 mm, demonstrating the ability to finely filter the fecal material.
Incorporation of cryoprotectants and freezing or freeze-drying steps
The method can further involve mixing the filtered fecal composition with cryoprotectants such as glycerol or trehalose, followed by freezing or freeze-drying to preserve the material.
Therapeutic efficacy of the prepared composition
The odorless human fecal composition prepared by this method is effective for treating Clostridium difficile infection, demonstrating its utility as a pharmaceutical therapeutic agent.
Particle size limitation of the composition
The collected fecal composition essentially contains no particles larger than 0.25 mm, ensuring a particle size suitable for oral administration and improved handling.
The claims cover a method of preparing an odorless, orally administrable human fecal pharmaceutical composition through progressive filtration, with optional incorporation of cryoprotectants and preservation steps. The composition maintains therapeutic efficacy for treating C. difficile infection and is characterized by a defined particle size limit.
Stated Advantages
The compositions are nearly odorless, improving aesthetic acceptability and ease of use in clinical or home settings.
Standardized preparation results in highly enriched microbiota compositions with significantly reduced non-living material, enhancing consistency and quality.
Frozen preparations allow for long-term storage and ready availability, removing delays and logistical challenges associated with fresh donor material.
Improved practicality and simplification of fecal microbiota transplantation (FMT) procedures by reducing donor screening burden and preparation complexity.
High efficacy in clearing recurrent Clostridium difficile infection, including in patients with inflammatory bowel disease, with overall success rates of approximately 95%.
Documented Applications
Treatment of recurrent Clostridium difficile infection and related colitis conditions such as autoimmune colitis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, and infectious colitis.
Replacing, supplementing, or modifying a subject's intestinal or colon microbiota to restore healthy gut flora.
Use as a medicament for diseases or pathological or iatrogenic conditions of the colon related to dysfunctional colon microbiota.
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