Synergistic bacterial compositions and methods of production and use thereof

Abstract

Provided are therapeutic compositions containing ecobiotic™ populations for prevention, treatment and reduction of symptoms associated with a dysbiosis of a mammalian subject such as a human.

1 . - 10 . (canceled) 
     
     
         11 . A therapeutic composition comprising an effective amount of a bacterial combination comprising a first purified bacterial population and a second purified bacterial population, the first purified bacterial population comprising a first 16S rDNA sequence at least 95% identical to a first member of a binary pair selected from Table 3 and the second purified bacterial population comprising a second16S rDNA sequence at least 95% identical to a second member of the binary pair selected from Table 3, wherein the binary pair can synergistically inhibit  Clostridium difficile  growth in a CivSim assay and wherein the therapeutic composition is formulated for oral delivery. 
     
     
         12 . The therapeutic composition of  claim 11 , wherein the binary pair can synergistically inhibit  Clostridium difficile  growth in a CivSim assay with a confidence interval of >99% (++++). 
     
     
         13 . The therapeutic composition of  claim 11 , wherein the first member has a 16S rDNA at least 95% identical to SEQ ID NO:705 or SEQ ID NO:1896. 
     
     
         14 . The therapeutic composition of  claim 11 , wherein the first member is a  Dorea longicatena.    
     
     
         15 . The therapeutic composition of  claim 11 , wherein the first 16S rDNA sequence is at least 97% identical to the first member of a binary pair selected from Table 3 and the second 16S rDNA sequence is at least 97% identical to the second member of the binary pair selected from Table 3. 
     
     
         16 . The therapeutic composition of  claim 11 , wherein the first 16S rDNA sequence is 100% identical to the first member of a binary pair selected from Table 3 and the second 16S rDNA sequence is 100% identical to the second member of the binary pair selected from Table 3. 
     
     
         17 . The therapeutic composition of  claim 11 , wherein at least one of the 16S rDNA sequences is a 16S rDNA V4 sequence. 
     
     
         18 . The therapeutic composition of  claim 11 , wherein at least one of the first purified bacterial population and the second purified bacterial population is capable of functionally populating a gastrointestinal tract of a human subject. 
     
     
         19 . The therapeutic composition of  claim 18 , wherein the functional populating of the gastrointestinal tract comprises reducing the number of one or more types of pathogenic bacteria in the gastrointestinal tract, and/or increasing the number of one or more non-pathogenic bacteria in the gastrointestinal tract. 
     
     
         20 . The therapeutic composition of  claim 11 , wherein the first purified bacterial population or the second purified bacterial population is a spore-forming bacteria. 
     
     
         21 . The therapeutic composition of  claim 11 , wherein the first purified bacterial population and the second purified bacterial population are both spore-forming bacteria. 
     
     
         22 . The therapeutic composition of  claim 11 , wherein the first purified bacterial population or the second purified bacterial population is in a spore form. 
     
     
         23 . The therapeutic composition of  claim 11 , wherein the first purified bacterial population and the second purified bacterial population are in a spore form. 
     
     
         24 . The therapeutic composition of  claim 11 , wherein the bacterial combination consists of the first and second bacterial populations. 
     
     
         25 . The therapeutic composition of  claim 11 , wherein the effective amount is 10̂8 or 10̂9 or 10̂10 total viable CFU of the bacterial combination. 
     
     
         26 . The therapeutic composition of  claim 11 , further comprising an effective amount of an anti-bacterial agent, an anti-fungal agent, an anti-viral agent or an anti-parasitic agent. 
     
     
         27 . The therapeutic composition of  claim 11 , formulated in a capsule. 
     
     
         28 . The therapeutic composition of  claim 27 , encapsulated in an enteric coating. 
     
     
         29 . A method of treating or preventing recurrence of  Clostridium difficile  infection in a gastrointestinal tract in a mammal, the method comprising administering the therapeutic composition of  claim 11  to the mammal. 
     
     
         30 . The method of  claim 29 , wherein the mammal is a human.