Blood as a route of transmission of uterine pathogens from the gut to the uterus in cows

BACKGROUND Metritis is an inflammatory disease of the uterus caused by bacterial infection, particularly Bacteroides, Porphyromonas, and Fusobacterium. Bacteria from the environment, feces, or vagina are believed to be the only sources of uterine contamination. Blood seeps into the uterus after calving; therefore, we hypothesized that blood could also be a seeding source of uterine bacteria. Herein, we compared bacterial communities from blood, feces, and uterine samples from the same cows at 0 and 2 days postpartum using deep sequencing and qPCR. The vaginal microbiome 7 days before calving was also compared. RESULTS There was a unique structure of bacterial communities by sample type. Principal coordinate analysis revealed two distinct clusters for blood and feces, whereas vaginal and uterine bacterial communities were more scattered, indicating greater variability. Cluster analysis indicated that uterine bacterial communities were more similar to fecal bacterial communities than vaginal and blood bacterial communities. Nonetheless, there were core genera shared by all blood, feces, vaginal, and uterine samples. Major uterine pathogens such as Bacteroides, Porphyromonas, and Fusobacterium were part of the core genera in blood, feces, and vagina. Other uterine pathogens such as Prevotella and Helcococcus were not part of the core genera in vaginal samples. In addition, uterine pathogens showed a strong and significant interaction with each other in the network of blood microbiota, but not in feces or vagina. These microbial interactions in blood may be an important component of disease etiology. The copy number of total bacteria in blood and uterus was correlated; the same did not occur in other sites. Bacteroides heparinolyticus was more abundant in the uterus on day 0, and both B. heparinolyticus and Fusobacterium necrophorum were more abundant in the uterus than in the blood and feces on day 2. This indicates that B. heparinolyticus has a tropism for the uterus, whereas both pathogens thrive in the uterine environment early postpartum. CONCLUSIONS Blood harbored a unique microbiome that contained the main uterine pathogens such as Bacteroides, Porphyromonas, and Fusobacterium. The presence of these pathogens in blood shortly after calving shows the feasibility of hematogenous spread of uterine pathogens in cows.