The effect of prepartum intravaginal bacteriophage administration on the incidence of retained placenta and metritis

The objective of this study was to evaluate the effect of prepartum intravaginal administration of an anti-Escherichia coli bacteriophage cocktail on uterine health and reproductive performance of lactating dairy cows. The study was conducted on a commercial dairy farm located near Ithaca, New York, from March to September 2012, and 107 cows were enrolled. The cows were divided randomly into 2 groups (treatment and control); treatment group cows were submitted to 3 intravaginal administrations of 20mL of a bacteriophage cocktail including 10 different phages in a lysate with titration of approximately 109 plaque-forming units, on d 230, 260, and 275 of gestation. Control cows were not treated with a placebo, and physical examination and sample collection was conducted equally for both groups. Vaginal swabs were collected at d 230, 260, and 275d of gestation, cervical swabs were collected at 3±1d in milk, and blood was collected at 275d of gestation for nonesterified fatty acids and interleukin (IL)-6 serum level measurements and at 10 DIM for β-hydroxybutyrate and IL-6 serum level measurements. The bacteriophage cocktail significantly increased the incidence of retained placenta and metritis. Swab samples were cultured for E. coli and no difference was found between treatment and control groups. The lysate contained 6×109 IU of lipopolysaccharide/mL and could have caused prepartum overstimulation of toll-like receptor-4 (TLR4)-chemokine pathway, leading to a weaker immune response. However, IL-6 was not affected by treatment, although sample size was insufficient to prove a treatment effect on the suppression of the chemokine cascade and innate immune system. Bacteriophage treatment had an excellent bactericidal effect in previous in vitro trials; however, special attention must be given to production of the cocktail to obtain a purified solution free of E. coli bacterial products and fragments, particularly lipopolysaccharide.