Compositions and methods for inhibition of pathogenic bacterial growth

Abstract

Compositions for methods of preventing or reducing pathogenic bacterial growth, proliferation, and/or colonization are described containing one or more types of non-pathogenic bacteria to be introduced into the gastrointestinal tract and effectively compete with pathogenic bacteria for monomeric or polymeric carbohydrate nutrients, and/or amino acid nutrients, and/or vitamin nutrients.

1 - 46 . (canceled) 
     
     
         47 . A composition comprising a population of bacteria, an excipient, and a capsule, wherein the population of bacteria comprises at least a first and second species of bacteria, wherein the first species of bacteria comprises a 16S rDNA sequence at least about 97% identical to SEQ ID NO: 559 and the second species of bacteria comprises a 16S rDNA sequence at least about 97% identical to SEQ ID NO: 593, and wherein the first and second species of bacteria are independently capable of proliferating in a nutrient medium having a threshold concentration of a nutrient below that concentration required for  Clostridium difficile  proliferation in the medium. 
     
     
         48 . The composition of  claim 47 , wherein the nutrient comprises a carbohydrate nutrient. 
     
     
         49 . The composition of  claim 47 , wherein the nutrient comprises a vitamin nutrient. 
     
     
         50 . The composition of  claim 47 , wherein the excipient is selected from the group consisting of a buffering agent, a preservative, a stabilizer, a binder, a compaction agent, a lubricant, a dispersion enhancer, a disintegration agent, a flavoring agent, a sweetener, a coloring agent and combinations thereof. 
     
     
         51 . The composition of  claim 47 , wherein the excipient comprises glycerol. 
     
     
         52 . The composition of  claim 47 , wherein the composition is formulated for oral administration to a mammalian subject. 
     
     
         53 . The composition of  claim 47 , wherein proliferation in the medium is determined by inoculating into the medium at least one bacteria selected from the group consisting of the first species of bacteria, the second species of bacteria, and  Clostridium difficile , culturing the at least one bacteria in the medium for a time period, measuring a titer of the at least one bacteria in the medium at several points over the time period, and calculating a growth rate as a difference in the titer over the time period. 
     
     
         54 . The composition of  claim 47 , wherein the first species of bacteria, the second species of bacteria, or both are in the form of spores. 
     
     
         55 . The composition of  claim 48 , wherein the carbohydrate is selected from the group consisting of N-Acetyl-D-Glucosamine, Thymidine, Uridine, Adenosine, Propionic Acid, Inosine, Pectin, and Butyric Acid. 
     
     
         56 . The composition of  claim 47 , wherein the first species of bacteria comprises a 16S rDNA sequence at least about 98% identical to SEQ ID NO: 559 or the second species of bacteria comprises a 16S rDNA sequence at least about 98% identical to SEQ ID NO: 593. 
     
     
         57 . The composition of  claim 47 , wherein the first species of bacteria comprises a 16S rDNA sequence at least about 98% identical to SEQ ID NO: 559 and the second species of bacteria comprises a 16S rDNA sequence at least about 98% identical to SEQ ID NO: 593. 
     
     
         58 . The composition of  claim 47 , wherein the first species of bacteria comprises a 16S rDNA sequence at least about 99% identical to SEQ ID NO: 559 or the second species of bacteria comprises a 16S rDNA sequence at least about 99% identical to SEQ ID NO: 593. 
     
     
         59 . The composition of  claim 47 , wherein the first species of bacteria comprises a 16S rDNA sequence at least about 99% identical to SEQ ID NO: 559 and the second species of bacteria comprises a 16S rDNA sequence at least about 99% identical to SEQ ID NO: 593. 
     
     
         60 . A method of reducing recurrence of  Clostridium difficile  infection in a mammalian subject in need thereof, the method comprising administering to the subject an effective amount of the composition of  claim 47 . 
     
     
         61 . The method of  claim 60 , wherein the method further comprises administering an anti-bacterial agent, an anti-fungal agent, an anti-viral agent, an anti-parasitic agent, or a combination thereof. 
     
     
         62 . The method of  claim 60 , wherein the composition is administered after an anti-bacterial agent, an anti-fungal agent, an anti-viral agent, an anti-parasitic agent, or a combination thereof. 
     
     
         63 . A method of treating a dysbiosis in a subject in need thereof, comprising administering to the subject an effective amount of the composition of  claim 47 . 
     
     
         64 . A single dose unit comprising a population of bacteria, wherein the population of bacteria comprise at least a first and a second species of bacteria, wherein the first species of bacteria comprises a 16S rDNA sequence at least about 97% identical to SEQ ID NO: 559 and the second species of bacteria comprises a 16S rDNA sequence at least about 97% identical to SEQ ID NO: 593, and wherein the first and second species of bacteria are independently capable of proliferating in a medium comprising a nutrient and having a threshold concentration of the nutrient below a concentration of the nutrient required for  Clostridium difficile  proliferation in the medium. 
     
     
         65 . A pharmaceutical formulation comprising the composition of  claim 47 . 
     
     
         66 . A method of producing a composition comprising a population of bacteria, comprising combining a first species of bacteria and a second species of bacteria, wherein the first species of bacteria comprises a 16S rDNA sequence at least about 97% identical to SEQ ID NO: 559 and the second species of bacteria comprises a 16S rDNA sequence at least about 97% identical to SEQ ID NO: 593, and wherein the first and second species of bacteria are independently capable of proliferating in a medium comprising a nutrient and having a threshold concentration of the nutrient below a concentration of the nutrient required for  Clostridium difficile  proliferation in the medium.