Norovirus study shows how bile acids in breast milk affect newborn gut health

A University of Florida researcher has conducted the first-ever study to identify the role of bile acids in breast milk, a breakthrough that could help reduce the incidence of the deadly norovirus in infants, which claims the lives of at least 50,000 children each year.

Because newborns lack an established gut microbiome (the collection of friendly bacteria that help humans digest nutrients and respond to gut pathogens), they are particularly susceptible to norovirus, a leading cause of newborn death worldwide.

“We knew that the microbiota protected adult mice from norovirus infection, and we knew that newborns were vulnerable to severe norovirus disease,” said Stephanie Karst, Ph.D., a member of the UF Emerging Pathogens Institute and professor in the UF College of Medicine who led a recent study of norovirus in a mouse model, published Aug. 29 in Cellular host and microbe“So this led us to ask the question: Are newborns vulnerable to norovirus because their gut microbiota is immature?”

The liver produces cholesterol, which is then converted into bile acids, metabolites that are secreted into the gut to help digest fats during meals. In the gut, certain microbiota then convert these bile acid metabolites into microbial bile acids, which may protect against norovirus infection. However, newborns do not have the appropriate gut bacteria to produce these protective microbial bile acids, leaving them unprotected against norovirus disease.

But the story doesn’t end there. While microbial bile acids play a protective role during norovirus infection, host bile acids actually promote infection. Newborns have high levels of these host bile acids, not only because they are not modified by gut bacteria, but also because they are found in breast milk.

According to Karst, “the severity of norovirus infection is determined by the balance between host bile acids that promote infection and microbial bile acids that inhibit it.”

Because newborns lack the proper gut microbes to modify bile acids and ingest host bile acids in breast milk, they have only the metabolites that make them susceptible to more severe norovirus infections.

Although noroviruses take advantage of this fragile metabolic environment in newborns, breastfeeding protects babies in many other ways, and the bile acids in milk likely have positive effects as well. In fact, Karst and his colleagues found that the acids protect babies from intestinal injury outside the context of a viral infection.

With further research into the maternal and neonatal bile acid landscape, Karst hopes the findings will inform future efforts to treat neonatal norovirus.

“The yin and yang — which makes norovirus infection worse but protects against other intestinal insults — really underscores the need for a holistic understanding,” Karst said. “Because we don’t want to manipulate the bile acid pool in breast milk and expose the baby to other types of intestinal damage.”

Norovirus is not the only virus influenced by metabolites such as bile acids. Influenza, chikungunya, and herpes viruses, for example, are inhibited by the same types of microbial bile acids that are not present in newborns. At the same time, host bile acids also promote human infection with the coronavirus.

“In addition, many other metabolites are passed to babies through breast milk,” Karst said. “I think this will hopefully open up other avenues of research into how metabolites interact with pathogens and how they influence the susceptibility of newborns.”