Cultivating Connections Between the Microbiome, Inflammation, and Reproductive Disease: A Comparative Perspective

Restricted (Penn State Only)
- Author:
- Lection, Jennine
- Graduate Program:
- Integrative and Biomedical Physiology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- April 23, 2024
- Committee Members:
- Gregory Shearer, Program Head/Chair
Erika Ganda, Chair & Co-Dissertation Advisr
William Staniar, Major Field Member
Adrian Barragan, Outside Field Member & Dissertation Advisor
Justin Silverman, Outside Unit Member - Keywords:
- Canine
Equine
Bovine
Microbiome
Inflammation - Abstract:
- The role of inflammation and bacteria in domestic animal reproduction is being reshaped. The immune response after parturition or after insemination allows for the maintenance of uterine health by removing remnants of placental tissue or clearing dead sperm. While normal levels of inflammation has been seen as a positive presence in the uterus, detecting bacteria in the uterus by culture-based techniques has been given one of two designations: 1) the bacteria are pathogenic and causing an infection, or 2) the bacteria are contamination either brought into the uterus from the vagina or contamination from sample handling. This oversimplification of the role of bacteria in the reproductive tract led to the overuse of antibiotics to treat positive bacterial cultures and has contributed to the global antibiotic-resistant bacteria crisis. However, with the ability to sequence DNA quickly and accurately, new possible roles for bacteria in the reproductive tract have emerged. The microbiome is simply a community of microorganisms that inhabit a certain environment, and based on next-generation sequencing techniques, the uterus has its own microbiome. The research across many species stops there – a few descriptive studies describing the organisms present in the uterus and their relative abundance, but the role of these newly-discovered inhabitants has not been fully realized. However, now that there is knowledge of a reproductive microbiome, it needs to be a consideration in new diagnostic and therapeutic plans. The impact of sequencing technologies will likely change what bacteria are seen as truly pathogenic and what bacteria are merely present as part of the local community. In order to maximize the benefit of studying the reproductive microbiome, each species unique pathophysiology needs to be considered. The rate of metritis in dairy cattle is around 20%, but that detrimental disease occurs less frequently in horses and dogs. One of the biggest concerns in equine reproduction is endometritis, which may be a concern in dogs, but the current methods of diagnosis are highly invasive, and so the disease is likely underdiagnosed. Pyometra is common in intact female dogs, but it occurs very rarely in horses and in less than 5% of dairy cattle. The role of inflammation and bacteria in each of these diseases is specialized to the species, and therefore, an approach to studying the microbiome needs to be equally as specialized. This dissertation explores the connections between infectious and inflammatory conditions of dairy cattle, mares and bitches and the role of the microbiome. In Chapter 3, the impact of an antibiotic alternative treatment, intrauterine dextrose, on the reproductive microbiome is evaluated as compared to the gold standard systemic antibiotic treatment. That chapter places special emphasis on whether known metritis-causing pathogens from the culture-based literature are enriched in either treatment group as compared to suspected metritis-associated pathogens from the culture-independent literature. Taking the idea of preventing antibiotic usage in dairy cattle one step further, Chapter 4 investigates whether a single dose of prepartum acetylsalicylic acid around fourteen days prior to calving can have a lasting impact after calving on both the reproductive microbiome as well as proinflammatory cytokine production. The analysis in that chapter focused around whether specific taxa from the microbiome have significant relationships with cytokines in order to understand which bacteria may be driving the inflammatory process during metritis. The final two chapters turn to other domestic animal species of interest. In Chapter 5, the first comparison is drawn of the fecal, vaginal, and uterine microbiomes in a group of similarly managed horses to be able to understand the influence of the gastrointestinal microbiome on the reproductive microbiome. A small number of mares with poor perineal conformation provide indication that further research is needed to understand which manure microbes are contaminating the reproductive tract and causing poor pregnancy rates. Lastly, Chapter 6 provides veterinarians with a profile of the canine vaginal resistome utilizing shotgun sequencing, thus digging further into the bacteria that are present in that environment that likely contribute to pyometra. Unsurprisingly, many of the classes of antibiotics that have high resistance profiles are commonly prescribed in small animal clinical practice. Next-generation sequencing technologies are going to revolutionize how veterinarians practice: how they interpret cultures, how they prescribe antibiotics, and how they view the health of an organ system. In order to get to that point of personalized medicine, animal health research needs to start to consider the impact of therapies on the microbiome. Many diseases in other organ systems have been connected to dysbiosis, or imbalance in the microbiome, in the gastrointestinal system, and in this dissertation, the aim is to cultivate similar connections to improve reproductive health and performance across dairy cattle, horses, and dogs.