Gut microbiome characteristics in pigs can potentially help improve outcome in those immunized against certain respiratory diseases.

"Our latest work is focused on how the gut microbiome impacts the response of growing pigs to a respiratory vaccine," Dr. Niederwerder said. "Beneficial microbes living in the gastrointestinal tract play an essential role in the development and regulation of immunity. We now understand that this role extends to viral respiratory vaccines in addition to viral respiratory diseases."

PRRSV and PCV2 are two of the most significant pathogens affecting swine production worldwide, resulting in clinical signs of respiratory disease and reduced weight gain. PRRSV is the most costly disease of swine in the U.S., with estimated losses of $664 million each year.

Modified live virus vaccines are widely used to reduce PRRS-associated losses and decrease respiratory disease in pigs. Currently available vaccines, however, are generally considered inadequate for disease control and additional tools are necessary to reduce the effects of PRRS on swine, she said.

"The gut microbiome is one alternative tool that can improve response to PRRSV vaccines and PRRSV infection," Dr. Niederwerder said. "In the current study, we identified several gut microbiome characteristics associated with improved growth rates of nursery pigs after PRRS vaccination and co-infection, including increased fecal bacterial diversity."

Further gut microbiome characteristics associated with increased growth rates of vaccinated pigs included increased Bacteroides pectinophilus, decreased Mycoplasmataceae species diversity, higher Firmicutes: Bacteroidetes ratios, increased relative abundance of the phylum Spirochaetes, reduced relative abundance of the family Lachnospiraceae, and increased Lachnospiraceae species C6A11 and P6B14.

The results of this study provide foundational evidence that the gut microbiome in swine plays a role in the efficacy of PRRS vaccines during a respiratory infection disease model.

"Identifying gut microbes which enhance efficacy of the currently available and widely-used PRRS vaccines is a way to improve the tools we already have in our toolbox for PRRS control," Dr. Niederwerder said. "Addressing complex infectious diseases require a multimodal approach and expanding the traditional methods by which we improve swine health benefits pigs and producers."

The article, "Gut microbiome associations with outcome following co-infection with porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) in pigs immunized with a PRRS modified live virus vaccine" was published in the March 2021 issue of Veterinary Microbiology. Co-authors include Drs. Laura A. Constance, James B. Thissen, Crystal J. Jaing, Kevin S. McLoughlin, Raymond R.R. Rowland, Nick V.L. Serão and Ada G. Cino-Ozuna.

Funding for the study was provided by the U.S. Department of Agriculture National Institute of Food and Agriculture; the state of Kansas National Bio and Agro-Defense Facility Fund; and by the Lawrence Livermore National Laboratory's Laboratory Derived Research and Development Effort.

The research team from 2019 (from left to right) Yi-Jun Lin, Yi-Hsien Cheng, Zhoumeng Lin, Miao Li, Wei-Chun Chou, Ning Xu.

Over the course of three years, the team led by Dr. Zhoumeng Lin, associate professor of pharmacology and toxicology and the principal investigator, has published three papers related to perfluorooctane sulfonate or PFOS. Considered a pollutant, PFOS is a member in the family of per- and polyfluoroalkyl substances (PFAS), which are human-made, persistent environmental contaminants and a global public health concern. The published manuscripts focused on creating models for utilization in human health risk assessments.

In 2019, the team published a study titled “Bayesian Evaluation of a Physiologically Based Pharmacokinetic (PBPK) Model for Perfluorooctane Sulfonate (PFOS) to Characterize the Interspecies Uncertainty between Mice, Rats, Monkeys, and Humans: Development and Performance Verification,” in the journal, Environment International. Available species-specific toxicokinetic data from other studies were used for model calibration and optimization, and independent datasets were used for model evaluation.

“This manuscript describes a physiologically based pharmacokinetic model for PFOS in mice, rats, monkeys and humans,” said Dr. Lin. “This model can be used to extrapolate toxicokinetic and toxicity data from animals to humans to support risk assessment and derivation of a new reference dose of PFOS, ultimately helping make public health decisions on this environmental contaminant.”

Dr. Lin’s team performed Bayesian statistical analysis using Markov chain Monte Carlo (MCMC) simulation to optimize the model and to characterize the uncertainty and interspecies variability of chemical specific parameters. The integrated and comparative analysis provides an important step towards improving interspecies extrapolation and quantitative risk assessment of PFOS, and this open-source model provides a foundation for developing models for other perfluoroalkyl substances. It was donned the Best Paper Award by Society of Toxicology Biological Modeling Specialty Section.

In 2020, the group followed up with a study titled “Probabilistic human health risk assessment of perfluorooctane sulfonate (PFOS) by integrating in vitro, in vivo toxicity, and human epidemiological studies using a Bayesian-based dose-response assessment coupled with physiologically based pharmacokinetic (PBPK) modeling approach,” published in Environment International. A Bayesian dose-response model was developed to analyze 34 studies, including human epidemiological, animal in vivo, and ToxCast in vitro toxicity datasets.

“The article describes a new probabilistic human health risk assessment method for PFOS that can be used to conduct dose-response analysis of different types of toxicity data,” said Dr. Wei-Chun Chou, research fellow in Institute of Computational Comparative Medicine (ICCM), department of anatomy and physiology, College of Veterinary Medicine and lead author of the series of manuscripts. “This includes high-throughput in vitro data, in vivo animal toxicity data, and human epidemiological data, and the dose-response analysis results can be linked to a PBPK model for subsequent risk assessment.”

The dose-response results were incorporated into a multi-species PBPK model to reduce the toxicokinetic/toxicodynamic uncertainties. In addition, a population-based probabilistic risk assessment of PFOS was performed for Asian, Australian, European, and North American populations, respectively, based on reported environmental exposure levels. The results provide insights into a complete risk characterization of PFOS and may help regulatory agencies in the reevaluation of PFOS risk.

The research team meets via Zoom to maintain social distancing while still working on their project(s). Top row, left to right: Qiran Chen, Zhoumeng Lin and Wei-Chun Chou. Bottom row: Long Yuan and Md Mahbubul Huq Riad.

The 2021 study, titled “Development of a Gestational and Lactational Physiologically Based Pharmacokinetic (PBPK) Model for Perfluorooctane Sulfonate (PFOS) in Rats and Humans and its Implications in the Derivation of Health-Based Toxicity Values” was recently accepted for publication in Environmental Health Perspectives. The focus of the study is developing a gestational and lactational PBPK model in rats and humans for PFOS to aid risk assessment in sensitive human subpopulations.

This study utilized existing PBPK models for PFOS, addressing a data gap of renal reabsorption and excretion in kidneys during gestation and lactation. The model was calibrated with previously published rat toxicokinetic and human biomonitoring data, and Monte Carlo simulation was used to address the inter individual variability. Model simulations were generally well correlated with observed PFOS concentrations in maternal/fetal/neonatal plasma and liver in rats and humans.

“The latest manuscript describes a PBPK model for PFOS in sensitive subpopulations, including pregnant women, fetuses, lactating women, and neonates,” said Dr. Lin. “This study provides a quantitative tool to aid risk re-evaluation of PFOS, especially in sensitive human subpopulations.”

The results support the importance of renal reabsorption/excretion during pregnancy and lactation in PFOS dosimetry, and suggest that the derivation of health-based toxicity values based on developmental toxicity studies should consider gestational/lactational dosimetry estimated from a life stage-appropriate PBPK model.

The DOI address of the 2019 manuscript is https://doi.org/10.1016/j.envint.2019.03.058, the 2020 manuscript https://doi.org/10.1016/j.envint.2020.105581, and the 2021 manuscript https://doi.org/10.1289/EHP7671.

Pet owners should be cautious about the following household dangers.

Medications can be poisonous

Human over-the-counter and prescription medications are also a common cause of poisoning in pets. Dr. Nelson said it is important to remember that pets, especially dogs, are not very discriminating about what they eat. It is not uncommon for dogs to swallow human medications, like anti-anxiety pills or pain medication, such as aspirin, ibuprofen or acetaminophen, while they are chewing on a bottle. This accidental ingestion can lead to gastrointestinal issues, organ failure and possibly death.

Owners often give human medications to their pets, such as aspirin or ibuprofen, to try help control their pain. Unfortunately, many of these medications are highly toxic to pets. Always consult with your veterinarian before giving any type of human medication to your pet.

"If your pet does accidentally consume human medication, call your veterinarian first, or a pet poison control hotline, before taking any type of action when this happens," Dr. Nelson said. "Know the name of the medication the pet swallowed and how much they ingested, if known, as that can make a big difference on treatment recommendations. Sometimes we will advise owners to induce vomiting at home, but it is done on a case-by-case basis as inducing vomiting in some instances can cause more harm."

Dr. Nelson also warns pet owners to be cautious of any flavored medication their pet may currently be taking. These medications are made to smell and taste good in order to make it easier to give them to pets. If they are left out, they will often be consumed all at once, which can possibly be harmful to a pet.

Separate people food from pet food

Many human foods are dangerous for pets. Some of the top foods on this list are chocolate, raisins, grapes, macadamia nuts, onions, garlic and yeast-based bread doughs, according to Dr. Nelson. Additionally, foods, candies, mouth washes and other medications that contain the artificial sweetener xylitol are also toxic to pets and can cause life-threatening low blood sugar and liver failure.

"Be aware of moldy and spoiled food, too," Dr. Nelson said. "Keep trash cans covered because pets are very good at getting into them and eating something they shouldn’t."

Skin protection

Commonly used products like bleach, all-purpose cleaners and other disinfectants can cause chemical burns on pets' skin and can be toxic if ingested. Dr. Nelson said this often happens because pets come into contact with the cleanser after the bottle spills on them, or they walk on a freshly washed floor or bathtub. Lysol can be toxic to cats when ingested, so it should be used very cautiously in households with cats.

“The best way to prevent such burns and toxic ingestion is to make sure surfaces are completely dry before letting pets on them and to tightly re-cap cleaning product bottles after using them,” Dr. Nelson said. “Just as with children, don’t forget to put such products away where pets can't get to them, and always remember to read the warning labels and instructions on all household cleansers before using them.”

Potential household hazards

Other common household toxins that owners might not think about are things like batteries, cigarettes and certain houseplants. If a pet ingests batteries, including button batteries, the battery acid can cause serious burns to their mouth, esophagus and stomach, Dr. Nelson said. They can also cause intestinal obstruction.

Common houseplants like philodendron and dieffenbachia are toxic to pets if ingested. Lilies can be especially dangerous to cats. It is a good idea to know what plants you have, both in your house and your yard, and if they are toxic to pets.

"Another thing to worry about is second-hand smoke," Dr. Nelson said. "Cats who have owners that smoke are twice as likely to develop malignant lymphoma than cats who have non-smoking owners. Be aware of cigarette butts that are left out because pets can develop nicotine poisoning if these are ingested."

Antifreeze is another potential danger for pets, especially for those who spend a lot of time outdoors or in the garage, Dr. Nelson said. Sometimes antifreeze will leak from a car onto the floor or into an existing puddle of water and pets may unintentionally drink it. A small amount of ingested antifreeze can be fatal to a dog or cat, causing the kidneys to shut down.

"Always keep antifreeze tightly sealed and out of reach from pets," Dr. Nelson said. "You also should check your vehicle frequently for antifreeze leaks. One should always make sure your pet has fresh drinking water available. However, the temptation to drink antifreeze will still be there, so prevention is key."

Cannabis (marijuana) has been legalized in many states now and veterinarians in those states are seeing a large increase in the number of pets being presented with marijuana toxicity. Pets are more sensitive to the effects of the THC in marijuana and it’s easier than you think for your pet, especially dogs, to consume a toxic amount.

Who to contact in an emergency

If your pet does come in contact with a dangerous material and you cannot reach your veterinarian, or your veterinarian is not familiar with the specific toxin or medication, Nelson recommends you call the Pet Poison Helpline 24/7 Animal Poison Control Center at 855-764-7661, or the American Society for the Prevention of Cruelty to Animals (ASPCA) Animal Poison Control hotline at 888-426-4435.

Submit nominations for Alumni Recognition Awards online

See our new online nomination form to nominate a fellow alumnus for one of our many annual recognition awards, presented at the national conferences: VMX, WVC, AVMA and the Annual Conference for Veterinarians. See full details at the link below.

https://www.vet.k-state.edu/asp/alumni-awards/awards.aspx .

Welcome to:

Brittney Flaherty, Organizational Support Services, USS Public Safety Officer
Anna Sommer, Veterinary Diagnostic Lab, Lab Technician
Sara Kessler, Diagnostic Medicine/Pathobiology, Research Assistant
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Melissa Dalton, Veterinary Health Center, Veterinary Assistant
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Farewell to:

Jodee Webster, Veterinary Diagnostic Lab, Lab Technician
Emily Herzfeld, Veterinary Health Center, Veterinary Nurse III