University of Nebraska Medical Center

Research Profiles: Dr. Jeffrey Salomon and Melissa Thoene

Dr. Jeffrey Salomon

Q&A with CHRI Scholar Dr. Jeffrey Salomon on Recently Published Research

Jeffrey Salomon, MD, assistant professor in the Division of Pediatric Critical Care Medicine and CHRI Scholar, is the first and corresponding author of an article titled, “Piglet cardiopulmonary bypass induces intestinal dysbiosis and barrier dysfunction associated with systemic inflammation,” in the May issue of Disease Models & Mechanisms.* In this Q&A Dr. Salomon addresses questions about his team’s novel study.

Q: You’ve been studying how cardiopulmonary bypass surgery (which is often required during cardiac surgery to repair heart defects) triggers systemic inflammation. Briefly, how do intestinal bacteria factor into that chain of events?  

A: The microbiome is associated with links with every major organ system in the body. We have identified bacterial and metabolite modifiers for inflammatory signaling in the gut. Children with heart defects also have more pro-inflammatory bacteria, which can create other inflammatory metabolites in the gut. Cardiopulmonary bypass also induces an intestinal barrier dysfunction leading to “gut leak”, which can allow bacteria, metabolites and toxins to leak out of the gut and interact with deeper tissues inducing a systemic response.

Q: What drew you to explore the piglet as an experimental animal model for cardiopulmonary bypass?

A: Piglets share very similar tissue, inflammatory responses and microbiome to humans. They are also an infant animal similar in size to neonates and young infants, which is when most cardiac repairs occur. One of my mentors at the University of Colorado has an established piglet model of cardiopulmonary bypass, so it was more feasible to collect the samples, send them to my lab and perform the analysis.

Q: What were your key findings in this initial piglet study, and where is it pointing for future studies?

A: We identified unique microbial shifts toward an increase in pro-inflammatory organisms even within four hours after cardiopulmonary bypass. We also demonstrated similar gut barrier dysfunction and gut leak as we see in our pediatric patients. Additionally, we identified reductions in short chain fatty acids, which are a gut and cardiac protective metabolite, and an increase in intestinal eicosanoids, which are pro-inflammatory gut metabolites. Mediation analysis showed the gut microbiome was responsible for a significant portion of the increase in some of the eicosanoids. We hope to replicate these results after we establish a similar piglet model of cardiopulmonary bypass here at UNMC and ultimately perform interventions on the gut to monitor downstream inflammatory signaling.

* Salomon, J. D., Qiu, H., Feng, D., Owens, J., Khailova, L., Osorio Lujan, S., Iguidbashian, J., Chhonker, Y. S., Murry, D. J., Riethoven, J. J., Lindsey, M. L., Singh, A. B., & Davidson, J. A. (2023). Piglet cardiopulmonary bypass induces intestinal dysbiosis and barrier dysfunction associated with systemic inflammation. Disease models & mechanisms, 16(5), dmm049742. https://doi.org/10.1242/dmm.049742 [doi.org]

Melissa Thoene

Q&A with Dr. Melissa Thoene on Research Published in Nutrients

A recent article in the journal Nutrients, “Plasma Retinol Concentrations and Dietary Intakes of Mother-Infant Sets in Singleton versus Twin Pregnancy,” includes research by several CHRI members in the Department of Pediatrics and the College of Allied Health Professions.* Senior author Melissa Thoene, PhD, assistant professor in the Division of Neonatology, discusses the project goals and outcomes here.

Q: Why is vitamin A (retinol) deficiency often a special challenge for mothers and infants during and after pregnancy?   

A: Vitamin A status is important to consider in a perinatal population given worsened fetal outcomes in states of deficiency or excess. Many recognize vitamin A deficiency (VAD) in less developed areas, but our research has observed a high prevalence of both vitamin A deficiency and insufficiency in a local delivering population. We're still learning all the reasons for this, but they may include malabsorption, disease states or low dietary intake of foods like vegetables that are high in vitamin A or provitamin A carotenoids. Furthermore, VAD deficient mothers may produce breast milk with lower content of vitamin A, increasing risk for deficiency in infants.

Q: What was your team’s experimental approach to compare vitamin A levels in twin versus singleton pregnancies?

A: There are no specific maternal dietary vitamin A recommendations for twin pregnancies, despite the increased demand for fetal growth. Thus, we aimed to evaluate if mothers and infants of twin pregnancies are at greater risk for low vitamin A status. We therefore analyzed raw maternal dietary intake and vitamin A concentrations in maternal and umbilical cord blood at time of delivery in singleton mother-infant dyads vs. twin mother-infant triads.

Q: What was your key discovery, and how do you see it potentially affecting clinical practice?

A: We observed significantly lower vitamin A blood concentrations in mothers and infants in twin pregnancies. Likewise, more twin vs. singletons had VAD for both mothers (57 vs. 7%) and infants (100% vs. 0%) despite similar maternal dietary vitamin A intake. This preliminary data highlights that multigestional mothers and infants are at greater risk for VAD. Future research should evaluate a larger population and if similar results are observed, it may indicate a need for specific (likely increased) dietary vitamin A recommendations for multigestational pregnancies.

* Akbar, A., Duvall, S., VanOrmer, M., Slotkowski, R., Hahka, T., Genaro-Mattos, T., Korade, Z., Hanson, C., Anderson Berry, A., & Thoene, M. (2023). Plasma Retinol Concentrations and Dietary Intakes of Mother-Infant Sets in Singleton versus Twin Pregnancy. Nutrients, 15(11), 2553. https://doi.org/10.3390/nu15112553 [doi.org]