Systemic antibiotic treatment of cows with metritis early postpartum does not change the progression of uterine disease or the uterine microbiome at 1 month postpartum

Abstract

Background: Postpartum uterine disease (metritis) is common in dairy cows. The disease develops within 1 week after calving and is associated with microbial dysbiosis, fever, and fetid uterine discharge. Cows with metritis have a greater likelihood of developing endometritis and infertility later postpartum. Antibiotic treatment is used to relieve symptoms of metritis but the capacity of antibiotic treatment to improve fertility later postpartum is inconsistent across published studies. We hypothesized that an antibiotic has only a short-term effect on the uterine microbiome and does not change the progression of disease from metritis to endometritis. To test this hypothesis, we studied the effects of systemic antibiotic given to cows diagnosed with metritis and healthy cows early postpartum on the development of endometritis and the uterine microbiome at 1 month postpartum. Results: Cows diagnosed with metritis were compared to healthy ones in a 2 x 2 factorial design, where they were either treated with an antibiotic (ceftiofur hydrochloride) at 7 to 10 days postpartum or left untreated. Cows were slaughtered at one month postpartum and the uterus was assessed for endometritis (presence of purulent material in the uterine lumen and inflammation in the endometrium) and uterine samples were collected for bacteriology and metagenomics (16S rRNA gene sequencing). As expected, the uterine microbiome at disease diagnosis had dysbiosis of typical metritis pathogens (e.g., Fusobacterium, Bacteroides, and Porphyromonas) in diseased compared with healthy cows. At one month postpartum, there was a tendency for more endometritis in metritis cows compared with healthy but antibiotic treatment had no effect on endometritis prevalence regardless of the original disease diagnosis. Likewise, when bacteria were cultured or sequenced, there were a greater number of species (culture) or amplicon sequence variants (ASV; sequencing) in the uterine lumen of cows with metritis. However, antibiotic treatment had no effect on the prevalence of cultured species or the composition of the detected ASV. The uterine microbiome at 1 month postpartum was associated with the clinical observation of the uterus (endometritis or healthy). Conclusions: Early postpartum antibiotic treatment only provides temporary resolution of uterine dysbiosis that is not sustained long-term. Failure to resolve the dysbiosis is associated with a greater prevalence of endometritis in cows with metritis, and the occurrence of endometritis significantly impacts fertility later postpartum.

The microbiome of the pregnant uterus in Holstein dairy heifers and cows assessed by bacterial culture and 16S ribosomal RNA gene sequencing

“…The number of sequence reads was low (median of 652 reads per sample) as has been reported for many other studies of the pregnant or non-pregnant uterus of the cow and other species ( Lietaer et al, 2021 ). For comparison, similar work on d 7 postpartum uterus (including metritic and non-metritic cows) returned a median of 220,548 reads per sample and later postpartum (d 30) the median was 9,343 reads per sample ( Moraes et al, 2024 ). Microbiome studies of tissues with a low microbial biomass are difficult to conduct because the potential for sample contamination from laboratory reagents is high ( Eisenhofer et al, 2019 ; O’Callaghan et al, 2020 ).…”

Adenomyosis and fibrosis define the morphological memory of the postpartum uterus of dairy cows previously exposed to metritis

“…; 2.2 mg/kg for 3 d)] or not treated (healthy, n = 5 and metritic, n = 5). Results from that experiment demonstrated no long-term effect of antibiotic treatment on a variety of study endpoints including uterine gene expression, microbiome, and inflammation (Moraes et al, 2024; Silva et al, 2024). Therefore, cows in Exp 2. were treated with ceftiofur hydrochloride at the discretion of the herdsman.…”