Ceftiofur reduced Fusobacterium leading to uterine microbiota alteration in dairy cows with metritis

Abstract

Background Metritis is an inflammatory uterine disease found in ~ 20% of dairy cows after parturition and associated with uterine microbiota with high abundance of Fusobacterium, Bacteroides, and Porphyromonas. Ceftiofur is a common treatment, but the effect on uterine microbiota is poorly understood. Herein, we investigated the short-term impact of ceftiofur on uterine microbiota structure and function in cows with metritis. Eight cows received ceftiofur (CEF) and 10 remained untreated (CON). Uterine swabs were collected for PCR and metagenomic analysis at diagnosis before treatment (5 ± 1 DPP) and 2 days after diagnosis/treatment (7 ± 1 DPP) from the same individuals. Seven CEF and 9 CON passed quality control and were used for 16S rRNA gene sequencing. Results Ceftiofur treatment resulted in uterine microbiota alteration, which was attributed to a decrease in relative abundance of Fusobacterium and in gene contents involved in lipopolysaccharide biosynthesis, whereas uterine microbiota diversity and genes involved in pantothenate and coenzyme A biosynthesis increased. Ceftiofur treatment also reduced rectal temperature and tended to reduce total bacteria in the uterus. However, other uterine pathogens such as Bacteroides and Porphyromonas remained unchanged in CEF. The blaCTX-M gene was detected in 37.5% of metritic cows tested but was not affected by CEF. We found that β-hydroxybutyric acid, pyruvic acid, and L-glutamine were preferentially utilized by Fusobacterium necrophorum according to metabolic activity with 95 carbon sources. Conclusions Ceftiofur treatment leads to alterations in the uterine microbiota that were mainly characterized by reductions in Fusobacterium and genes involved in LPS biosynthesis, which may be associated with a decrease in rectal temperature. The increase in pantothenate and coenzyme A biosynthesis indicates microbial response to metabolic stress caused by ceftiofur. Preference of Fusobacterium for β-hydroxybutyric acid may help to explain why this strain becomes dominant in the uterine microbiota of cows with metritis, and it also may provide a means for development of new therapies for the control of metritis in dairy cows.

Bovine Animal Model for Studying the Maternal Microbiome, in utero Microbial Colonization and Their Role in Offspring Development and Fetal Programming

“…A longitudinal survey of bovine reproductive microbiota at the time of breeding and during pregnancy can provide important information that can be translated into human maternal practices. Vaginal swab (Amat et al, 2021b), cervical swab (Wang et al, 2018), uterine swab (Jeon et al, 2021), and endometrial brush (Pascottini et al, 2020) sampling from pregnant cattle allow monitoring of the changes in microbiota residing in each of the anatomical sites along the reproductive tract. Applying targeted alterations of vaginal and uterine microbiota during early or late gestation with probiotics or antibiotics will allow for studying the impact of maternal microbiota on pregnancy and health of the dams, and on fetal programming and offspring development.…”

Oxidative Stress in Dairy Cows: Insights into the Mechanistic Mode of Actions and Mitigating Strategies

“…Therefore, special attention should be paid to this taxa when planning mitigation strategies. Out of 95 carbon energy sources investigated that may promote the growth of Fusobacterium , up to 47 were metabolized by F. necrophorum , enabling it to proliferate in postpartum cows using an array of energy sources, even in animal NEB [ 36 ]. For instance, in iron-limited conditions where F. necrophorum thrived, an increase of the expression of virulence genes such as the glycoprotein of influenza virus called haemagglutinin and leukotoxin genes was reported (2.49 and 3.72 fold increase respectively [ 37 ]).…”

The Endometrial Microbiota—16S rRNA Gene Sequence Signatures in Healthy, Pregnant and Endometritis Dairy Cows

“…The findings of these culture-dependent studies have recently been corroborated and expanded by 16S rRNA amplicon-based sequencing. These 16S rRNA gene-based studies reveal a larger intrauterine bacterial population diversity and a more detailed and complex structure of the uterine microbiota in both metritis and healthy cows [ 6 , 10 , 11 , 12 , 13 ]. Moreover, the finding of bacteria in the uterus of virgin heifers and pregnant cows challenges the hypothesis that a sterile uterus is required for the establishment and maintenance of pregnancy [ 7 , 14 , 15 ].…”