Penn Vet’s New Center for Host Microbial Interactions
November 5, 2013, Volume 60, No. 12
By current estimates, the human body contains ten times more bacterial cells than human cells. Acting in ways both beneficial and harmful, this complex ecosystem of microorganisms—collectively called the microbiome—lives on the surface of the skin and in the gut and urogenital tract where it influences digestion, allergies and a multitude of diseases. At Penn Vet, researchers are exploring the microbiome of animals in order to benefit both animal and human health.
Penn Vet’s new Center for Host Microbial Interactions (CHMI), a unique venture for any veterinary school, is designed to facilitate collaborative projects that leverage genomics to study the intersection of microbes and disease. In doing so, researchers will gain insight into how bacteria, parasites, viruses and other organisms interact with their animal and human hosts in ways that either maintain health or lead to disease.
The Penn community is invited to a symposium that CHMI is hosting on Thursday, November 7 from 4-6 p.m. at the Hill Pavilion.
The Center is currently funding five pilot projects. Each year, the Center will invite researchers to submit proposals for funding. In addition to these pilots, the Center provides ongoing support and training for Penn Vet faculty and their labs to carry out analyses of the complex datasets generated by genomic approaches.
“We strongly believe this innovative approach to health and disease will provide new insights into animal and human health and will build on the One Health concept, linking veterinary medicine, human medicine and environmental science, in a novel and impactful way,” said Joan C. Hendricks, the Gilbert S. Kahn Dean of Veterinary Medicine.
The five pilot projects, each led by Penn Vet faculty, will probe the following interactions:
• Canine atopic dermatitis as a model for human dermatology
Canine atopic dermatitis is a common allergic skin condition that is similar to human atopic dermatitis. Veterinarians at Penn Vet’s Ryan Hospital treat dogs that present with typical symptoms such as itching and then progress to scabs, hair loss and secondary bacterial infections that can often be resistant to antibiotic treatments. Penn Vet faculty Dr. Charles Bradley, Dr. Elizabeth Mauldin, Dr. Dan Morris and Dr. Shelley Rankin are collaborating with Dr. Elizabeth Grice of the Perelman School of Medicine to examine the ecosystem of bacteria on the dogs’ skin and monitor changes in the microbiome of each dog during treatment. The goal is to understand the role of resident microbial organisms in resistance to infection, the onset of infection and the development of antimicrobial resistance once infection occurs.
Very little is known about the dog microbiome. Since dogs develop spontaneous and complex diseases, much like humans, they serve as ideal models for understanding how both animals and humans can go from being healthy one day to dealing with a chronic or recurring disease the next day.
• Digestion, productivity and health in dairy cows
Dr. Dipti Pitta sees a direct connection between the gastrointestinal microbiome in cattle and the animal’s ability to process food, thrive and produce milk and meat—a critical part of the global food supply.
As a ruminant, the cow’s digestive tract offers a rich source of information pertinent to the study of microbial environments. Dairy cows are more prone to metabolic problems immediately after calving, as the animal has to adapt quickly from a non-lactating to a lactating phase. The “dry” cow’s nutritional needs are much less than those producing milk, so lactating cows are generally fed a much higher energy diet than dry cows. Dr. Pitta is studying the effect of changes in diet and metabolism that occur during the transition from dry to lactation period on the microbial populations, as these are the mechanisms that drive the fermentation processes to release substrates required for producing milk.
• Maternal stress and its impact on neurological health of offspring
Dr. Tracy Bale is examining the relationship between early prenatal stress, the mother’s vaginal microbiome and her offspring’s brain development. Dr. Bale believes that, because a baby’s gut is first colonized by bacteria from the mother’s vagina at birth, perhaps differences are produced in the population of microbes by a mother’s stress and can lead to changes in a baby’s own gut microbiome. This altered microbial community could then lead to differences in how important nutrients are absorbed in the offspring’s body, leading to differences in how the baby’s brain develops.
• Pre-operative antibiotics and the equine gut microbiome
Previous research has linked high-carbohydrate feed to the development of colitis in horses. This may have to do with how a change in diet leads to alterations in the population of microbes living in the gastrointestinal tract, ultimately tipping the balance from health to disease. Likewise, administering pre-operative antibiotics could also lead to gut microbiome imbalances. Dr. Julie Engiles will take fecal and serum samples from subjects at New Bolton Center and track variations in the horses’ gut microbiome at certain times after surgery. If, unfortunately, a horse develops an infection after its procedure, Dr. Engiles and her colleagues will evaluate whether the infectious agents match up to those in the gut or whether they match other microbes.
The study will also track horses to see if they develop other post-operative complications, including two of the most troublesome maladies that strike horses: colic and laminitis.
• Stem cell transformation and colorectal cancer
Prior research conducted by Dr. Christopher Lengner has shed light on the idea that most cases of colorectal cancer may originate from a mutation in a stem cell that leads to unrelated growth. Yet other research has indicated that chronic inflammation, inspired by an immune response to gut bacteria, may also play a leading role in increasing cancer risk. The goal of Dr. Lengner’s latest research project is to reconcile these two ideas.
This project will involve experimentally manipulating expression of the protein Msi, which Dr. Lengner’s lab has previously found to bind directly to RNA molecules that are involved in regulating immune responses. Dr. Lengner and his colleagues will track the response of the microbial communities as Msi levels are either knocked down or overexpressed. What they find may lead to the pursuit of other questions, such as how tumor development progresses in the presence or absence of various microbial communities.