CHAMPAIGN, Ill. — In a study of newborn piglets, infection with influenza A was associated with disruptions in the piglets’ nasal and gut microbiomes and with potentially detrimental changes in gene activity in the hippocampus, a brain structure that plays a central role in learning and memory. Maternal vaccination against the virus during pregnancy appeared to offer some protection from those changes in the piglets.
The findings are reported in the journal Veterinary Microbiology.
According to the Centers for Disease Control and Prevention, children under six months of age are at the highest risk of hospitalization from infection with the influenza A virus. Because newborns have underdeveloped immune systems, they are susceptible to a host of complications from infection, including brain inflammation, which can be fatal in rare cases and may interfere with normal brain development in those who survive.
Infants infected with the influenza A virus in the first six months of life are more likely than others to experience long-term complications, including diabetes, asthma, allergies and cognitive defects. Vaccination against the influenza A virus in pregnancy is the most effective way to protect offspring from these complications, said Ying Fang, a professor of pathobiology at the University of Illinois Urbana-Champaign who led the research with U. of I. pathobiology professor Christopher Gaulke.
Fang, a microbiologist who studies pathogenic viruses, is working to produce a new vaccine against the influenza A virus, a version of which was used to vaccinate pregnant sows in the study. Gaulke, a microbiologist, studies the role of the microbiome in health and disease.
Previous studies have linked disease-related alterations of the gut microbiome to changes in brain gene expression, but most of these studies were conducted in adults, the researchers said.
“We are the first to use a neonatal piglet model to study the interaction between the microbiome and brain gene function,” Fang said. Pigs make a good animal model for studying human infections because they are physiologically very similar to humans and are susceptible to many of the same zoonotic viruses, she said.
The researchers focused on the hippocampus, relying on the expertise of Illinois animal sciences professor and study coauthor Adrienne Antonson, who explores the prenatal origins of neurodevelopmental and behavioral disorders. Previous work from Antonson’s lab found that a viral infection during pregnancy can disrupt piglets’ hippocampal development and function.
The microbiome also appears to play an important role in normal brain development, Gaulke said.
“Numerous studies have found associations between the microbiome and normal brain development across the lifespan, particularly in early life,” he said. “It seems that the microbiome is involved in getting things set up properly. And if you disrupt the microbiome in animal models, you can have negative outcomes, including neurocognitive defects.”
For the new study, the team compared alterations to the microbiome and to hippocampal gene-expression in the offspring of vaccinated and unvaccinated sows after the piglets were exposed to the influenza A virus. A third group of uninfected piglets whose mothers had been given a “mock” vaccine during pregnancy served as a control group.
The team found distinct differences in the piglets’ gut and nasal microbiota and hippocampal gene expression after infection. While health-promoting microbes in the nose and in the gut increased in abundance in all groups after infection, the effect was blunted in the offspring of unvaccinated sows. Similarly, infected piglets from unvaccinated sows saw a greater increase in potentially pathogenic microbes — particularly in the nose. The changes in the nasal cavity also corresponded most closely with potentially problematic changes in gene expression in the hippocampus, the researchers report.
“We knew that influenza infection in pregnancy and in newborns can have negative effects on an infant’s brain function and development, both immediately and later in life,” Gaulke said. “We also knew that the microbiome is involved in early brain development, and that influenza can impact respiratory and gut microbiota. However, no one had put all of this together in a neonatal model. Our study was able to look at how the microbiome may contribute to hippocampal function in the context of this disease.”
The findings suggest that maternal vaccination blunts the potentially damaging effects of influenza infection on the microbiome and on the hippocampus in the offspring, the researchers said. Further studies are needed to determine the exact mechanisms by which influenza A viral infection leads to these and/or other changes in the microbiome, and whether and how those changes influence brain health.
Fang and Gaulke also are professors in the Carl R. Woese Institute for Genomic Biology at the U. of I.
The National Institutes of Health supported this research.
Editor’s note:
To reach Ying Fang, email yingf@illinois.edu.
To reach Christopher Gaulke, email cgaulke@illinois.edu.
The paper “Maternal vaccination partially protects piglets against influenza A virus associated alteration of the microbiome and hippocampal gene expression” is available online or from the U. of I. News Bureau.
