Use of bacterial endotoxins and lipoteichoic acids to improve postpartal health and productivity of dairy cows and their newborns

Abstract

A combination of a bacterial endotoxin, in particular a lipopolysaccharide, and a lipoteichoic acid for treating or preventing a metabolic disorder or bacterial infection, or for improving milk energy efficiency in a subject. The combination may be administered separately, simultaneously or sequentially to a subject.

1 . A combination comprising a bacterial endotoxin and a lipoteichoic acid, said combination being for separate, simultaneous or sequential administration to a subject for treating or preventing a metabolic disorder, for treating or preventing bacterial infection or for improving milk energy efficiency in said subject. 
     
     
         2 . The combination according to  claim 1 , wherein said endotoxin is a lipopolysaccharide. 
     
     
         3 . The combination according to  claim 1 , wherein said bacterial endotoxin is derived from a gram-negative bacterium. 
     
     
         4 . The combination according to  claim 3 , wherein said gram-negative bacterium is  Escherichia coli.    
     
     
         5 . The combination according to  claim 1 , wherein said endotoxin is a naturally-occurring, semi-synthetic or synthetic endotoxin and wherein said lipoteichoic acid is a naturally-occurring, semi-synthetic or synthetic lipoteichoic acid. 
     
     
         6 . The combination according to  claim 1 , wherein said lipoteichoic acid is derived from a gram-positive bacterium. 
     
     
         7 . The combination according to  claim 6 , wherein said gram-positive bacterium is  Bacillus subtilis.    
     
     
         8 . The combination according to  claim 1 , said combination being formulated for administration to the mucosal tissues (including gastrointestinal tract). 
     
     
         9 . The combination according to  claim 1 , said combination being formulated for oral or nasal administration. 
     
     
         10 . The combination according to  claim 9 , said combination being formulated as a tablet, capsule or liquid formulation. 
     
     
         11 . A method for treating or preventing a metabolic disorder, for treating or preventing bacterial infection or for improving milk energy efficiency in a subject, said method comprising administering to said subject a bacterial endotoxin and a lipoteichoic acid, separately, simultaneously or sequentially. 
     
     
         12 . The method according to  claim 11 , wherein said metabolic disorder is associated with parturition. 
     
     
         13 . The method according to  claim 11 , wherein said metabolic disorder is metritis, laminitis, retained placenta or impaired uterine horn fluctuation. 
     
     
         14 . The method according to  claim 11 , wherein said milk energy efficiency comprises increased fat to protein ratio or increased milk fat efficiency. 
     
     
         15 . The method according to  claim 11 , comprising administering said combination to said subject from a time no more than four weeks prior to parturition to a time no more than four weeks after parturition. 
     
     
         16 . The method according to  claim 11 , comprising administering said combination in an endotoxin dose of from 0.001 to 1 μg endotoxin/kg body weight of said subject. 
     
     
         17 . The method according to  claim 16 , wherein said endotoxin dose comprises about 0.01, about 0.05 or about 0.1 μg endotoxin/kg body weight of said subject. 
     
     
         18 . The method according to  claim 11 , comprising administering said combination in a lipoteichoic acid dose of from 0.1 to 1000 μg lipoteichoic acid. 
     
     
         19 . The method according to  claim 18 , wherein said lipoteichoic acid dose comprises about 100, about 120 or about 250 μg lipoteichoic acid. 
     
     
         20 . The method according to  claim 11 , wherein said subject is a dairy cow.