Methods of Populating a Gastrointestinal Tract

Abstract

Methods and compositions for populating the gastrointestinal tract of a subject are described. Methods include administering to a subject a therapeutic composition comprising a purified population of spore-forming bacteria produced by providing a fecal material and subjecting the material to a treatment step resulting in purification of spore-form ing bacteria. Methods include administering an amount effective to engraft and/or augment in the gastrointestinal tract in order to treat or prevent a dysbiosis in the mammalian subject.

1 - 22 . (canceled) 
     
     
         23 . A therapeutic composition comprising a purified population of spore-forming bacteria or bacteria having a substantial activity of spore-forming bacteria, in an amount effective to populate the gastrointestinal tract of a mammalian subject to whom the therapeutic composition is administered. 
     
     
         24 . The therapeutic composition of  claim 23 , wherein the purified population is effective to i) treat a gastrointestinal dysbiosis; ii) engraft at least one type of bacteria present in the therapeutic composition but not present in a mammalian subject prior to treatment; and/or iii) augment at least one type of bacteria not present in the therapeutic composition in a mammalian subject to whom the therapeutic composition is administered. 
     
     
         25 . (canceled) 
     
     
         26 . The therapeutic composition of  claim 23 , wherein the populating of the gastrointestinal tract is effective to i) engraft at least one type of bacteria present in the therapeutic composition but not present in a mammalian subject; ii) augment at least one type of bacteria not present in the therapeutic composition in the mammalian recipient; and/or iii) reduce the severity of at least one symptom of a gastrointestinal dysbiosis. 
     
     
         27 . The therapeutic composition of  claim 23 , wherein the purified population comprises a population of bacterial spores or a bacterial spore preparation. 
     
     
         28 . (canceled) 
     
     
         29 . The therapeutic composition of  claim 23 , wherein the purified population is purified from a fecal material obtained from a mammalian donor subject. 
     
     
         30 - 36 . (canceled) 
     
     
         37 . The therapeutic composition of  claim 24 , wherein the gastrointestinal dysbiosis comprises a gastrointestinal disease, disorder or condition selected from the group consisting of  Clostridium difficile -induced diarrhea, irritable bowel syndrome (IBS), colonization with a pathogen or pathobiont, infection by a drug-resistant pathogen or pathobiont, colitis, and Crohn's Disease. 
     
     
         38 - 39 . (canceled) 
     
     
         40 . The therapeutic composition of  claim 29 , wherein the purified population comprises reduced residual habitat product, wherein the residual habitat product is reduced by at least 5% from the fecal material obtained from the mammalian donor subject. 
     
     
         41 - 52 . (canceled) 
     
     
         53 . The therapeutic composition of  claim 23 , wherein the purified population is obtained by the steps of a) providing a fecal material comprising spore-forming bacteria and b) subjecting the fecal material to a treatment step resulting in purification of the spore-forming bacteria. 
     
     
         54 . (canceled) 
     
     
         55 . The therapeutic composition of  claim 53 , wherein the treatment step comprises a heat treatment, mechanical treatment, or solvent treatment. 
     
     
         56 . The therapeutic composition of  claim 23 , wherein the composition optionally comprises a germinant. 
     
     
         57 - 70 . (canceled) 
     
     
         71 . A method for production of a composition comprising a population of bacterial spores suitable for therapeutic administration to a mammalian subject in need thereof, comprising the steps of: (a) providing a fecal material obtained from a mammalian donor subject; and (b) subjecting the fecal material to at least one purification step under conditions such that a purified population of spore-forming bacteria is produced from the fecal material. 
     
     
         72 . The method of  claim 71 , wherein the mammalian donor subject is a healthy human subject. 
     
     
         73 . The method of  claim 71 , comprising contacting the fecal material or a fraction or derivative thereof with a miscible solvent. 
     
     
         74 . The method of  claim 71 , wherein the at least one purification step comprises a miscible solvent treatment, an immiscible solvent extraction, an elution from a solid medium, a thermal disrupting treatment, a radiation treatment, a filtration treatment, a chromatographic separation treatment, a centrifugation treatment, an aqueous extraction treatment, a solvent-aqueous extraction treatment, mechanical disrupting treatment, or a combination thereof. 
     
     
         75 - 76 . (canceled) 
     
     
         77 . The therapeutic composition of  claim 23 , wherein the spore-forming bacteria or bacteria having a substantial activity of spore-forming bacteria comprise bacteria from the genera provided in Table 1. 
     
     
         78 - 80 . (canceled) 
     
     
         81 . The therapeutic composition of  claim 23 , wherein the purified population comprises at least about 1×10 3  bacterial spores. 
     
     
         82 - 83 . (canceled) 
     
     
         84 . The therapeutic composition of  claim 23 , wherein the purified population is effective to treat or prevent a metabolic disorder in a mammalian recipient subject suffering from or at risk of developing such disorder to whom the therapeutic composition is administered. 
     
     
         85 . (canceled) 
     
     
         86 . A kit comprising in one or more containers a fecal material collection apparatus and a solvent solution, and instructions for use thereof for generating purified populations of spore-forming bacteria. 
     
     
         87 - 106 . (canceled) 
     
     
         107 . The therapeutic composition of  claim 23 , wherein the purified population comprises at least a first type of isolated bacteria and a second type of isolated bacteria and wherein the first type of isolated bacteria and the second type of isolated bacteria comprise an operational taxonomic unit (OTU) distinction. 
     
     
         108 . The therapeutic composition of  claim 107 , wherein the OTU distinction comprises a 16S rRNA sequence similarity below about 97% identity. 
     
     
         109 - 120 . (canceled)