Elimination of colonic bacterial driving lethal inflammatory cardiomyopathy

Abstract

The invention relates to methods, kits and compositions for reducing the level of or eliminating Bacteroides in situ. The invention encompasses methods of preventing myocarditis, treating myocarditis or dilated cardiomyopathy, or limiting progression of myocarditis toward dilated cardiomyopathy in a subject in need thereof, comprising reducing the amount of Bacteroides sp. in the subject. The invention further encompasses methods of diagnosis of a subject as having myocarditis or dilated cardiomyopathy. The invention also encompasses compositions preventing myocarditis, treating myocarditis or dilated cardiomyopathy, or limiting progression of myocarditis toward dilated cardiomyopathy in a subject in need thereof.

We claim: 
     
         1 . A method of preventing myocarditis in a subject in need thereof, comprising reducing the amount of  Bacteroides  sp. in a subject. 
     
     
         2 . A method of treating myocarditis or DCM in a subject in need thereof, comprising reducing the amount of  Bacteroides  sp. in a subject. 
     
     
         3 . A method of limiting progression of myocarditis toward DCM in a subject in need thereof, comprising reducing the amount of  Bacteroides  sp. in a subject. 
     
     
         4 . A method of diagnosis a subject as having myocarditis or DCM, comprising obtaining a biological sample of the subject, quantifying the amount of  Bacteroides  sp. in the biological sample relative to a control sample. 
     
     
         5 . The method of  claim 1 , comprising administering to the subject an effective amount of an antibiotic, phage, recombinant phage, packaged phagemid, bacteria, engineered bacteria, bacteriocin or endolysin. 
     
     
         6 . The method of  claim 2 , comprising administering to the subject an effective amount of an antibiotic, phage, recombinant phage, packaged phagemid, bacteria, engineered bacteria, bacteriocin or endolysin. 
     
     
         7 . The method of  claim 3 , comprising administering to the subject an effective amount of an antibiotic, phage, recombinant phage, packaged phagemid, bacteria, engineered bacteria, bacteriocin or endolysin. 
     
     
         8 . The method of  claim 4 , comprising administering to the subject an effective amount of an antibiotic, phage, recombinant phage, packaged phagemid, bacteria, engineered bacteria, bacteriocin or endolysin. 
     
     
         9 . The method of  claim 5 , wherein the antibiotic is selected from streptomycin, vancomycin, clindamycin, metronidazole, sulphadoxine, trimethoprim, or any combination of 1, 2, 3, 4, 5 or 6 of these antibiotics. 
     
     
         10 . The method of  claim 6 , wherein the antibiotic is selected from streptomycin, vancomycin, clindamycin, metronidazole, sulphadoxine, trimethoprim, or any combination of 1, 2, 3, 4, 5 or 6 of these antibiotics. 
     
     
         11 . The method of  claim 7 , wherein the antibiotic is selected from streptomycin, vancomycin, clindamycin, metronidazole, sulphadoxine, trimethoprim, or any combination of 1, 2, 3, 4, 5 or 6 of these antibiotics. 
     
     
         12 . The method of  claim 8 , wherein the antibiotic is selected from streptomycin, vancomycin, clindamycin, metronidazole, sulphadoxine, trimethoprim, or any combination of 1, 2, 3, 4, 5 or 6 of these antibiotics. 
     
     
         13 . The method of  claim 5 , wherein the phage, recombinant phage or packaged phagemid encodes a nuclease selected from CRISPR-Cas, TALENs and variants, zinc finger nuclease (ZFN) and ZFN variants, natural, evolved or engineered meganuclease or recombinase variants. 
     
     
         14 . The method of  claim 6 , wherein the phage, recombinant phage or packaged phagemid encodes a nuclease selected from CRISPR-Cas, TALENs and variants, zinc finger nuclease (ZFN) and ZFN variants, natural, evolved or engineered meganuclease or recombinase variants. 
     
     
         15 . The method of  claim 7 , wherein the phage, recombinant phage or packaged phagemid encodes a nuclease selected from CRISPR-Cas, TALENs and variants, zinc finger nuclease (ZFN) and ZFN variants, natural, evolved or engineered meganuclease or recombinase variants. 
     
     
         16 . The method of  claim 8 , wherein the phage, recombinant phage or packaged phagemid encodes a nuclease selected from CRISPR-Cas, TALENs and variants, zinc finger nuclease (ZFN) and ZFN variants, natural, evolved or engineered meganuclease or recombinase variants. 
     
     
         17 . The method of  claim 5 , wherein the  Bacteroides  is  B. thetaiotaomicron  and/or  B. faecis.    
     
     
         18 . The method of  claim 6 , wherein the  Bacteroides  is  B. thetaiotaomicron  and/or  B. faecis.    
     
     
         19 . The method of  claim 7 , wherein the  Bacteroides  is  B. thetaiotaomicron  and/or  B. faecis.    
     
     
         20 . The method of  claim 8 , wherein the  Bacteroides  is  B. thetaiotaomicron  and/or  B. faecis.