Researchers at Vanderbilt University Medical Center are examining a key oligosaccharide in human milk that promotes growth in infants and has the potential to address adult diseases.
This component – 2’-fucosyllactose (2’-FL) – is one of the most abundant of the numerous human milk oligosaccharides (HMOs) and is known to encourage growth of commensal bacteria, protect the intestinal barrier, and decrease susceptibility to inflammation.
Someday, it may be useful in treatment of adult inflammatory bowel disease (IBD), said Fang Yan, M.D., Ph.D., a professor of pediatric gastroenterology at Vanderbilt whose earlier work focused on understanding the mechanisms underlying IBD and how probiotics might help mitigate the disease.
“Human milk oligosaccharides have shown high impact in infant growth and intestinal integrity,” Yan said. “But what might be the health outcomes in adults? That was the origin of this project.”
“Human milk oligosaccharides have shown high impact in infant growth and intestinal integrity. But what might be the health outcomes in adults?”
Yan conducted the research with Sari A. Acra, M.D., director of the Division of Pediatric Gastroenterology at Monroe Carell Jr. Children’s Hospital at Vanderbilt. Their work was recently published in ASM’s mBio journal.
“We do know that human milk oligosaccharides in infants promote a healthy GI environment,” Acra said. “There are other global benefits, as well, such as improved neurocognitive development. HMOs have even been added to commercial infant formulas. This study, using a mouse model, looked at possible benefits in adults from early exposure to these healthy molecules, with a focus on IBD.”
Acra added that 2’-FL acts as a prebiotic, because it passes undigested to the colon and becomes food for healthy bacteria.
Genome sequencing identified the bacteria involved, in particular Bifidobacterium infantis. Researchers also identified metabolic pathways and metabolites such as pantothenate – or vitamin B5 – that were part of the mechanism.
“Bifidobacterium infantis has a gene allowing it to metabolize 2’-FL,” Yan said. “So, 2’-FL can promote the colonization of B. infantis and other species.”
One of the metabolites produced, pantothenate, has beneficial effects related to inflammation and can decrease oxidative stress, which is a characteristic marker for several diseases, she said. Disruption of the intestinal barrier function is another sign.
Yan and her colleagues also used AI technology in studying metabolic pathways in IBD patients. They found some of those pathways weakened, but hypothetically 2’-FL can help compensate and thus improve symptoms.
“We chose the most abundant oligosaccharide with known benefits to infants and a potential intersection with IBD pathophysiology, and we tested its theoretical benefit,” Acra said. “In this mouse study, our hypothesis has been supported.”
Since most adult humans do not encounter 2’-FL, it could be administered as a treatment, using a synthetic form because HMOs are difficult to isolate from milk, Yan said.
Her team collaborates with Steven D. Townsend, Ph.D., a professor of chemistry at Vanderbilt, who specializes in synthesizing these molecules by generating recombinant protein from E. coli.
“Eventually it will probably be a product you can take as a pill,” said Acra. “It has to be in a form that can survive the transit through the small intestine and then release in the large intestine.”
Such a pill might contain healthy bacteria along with 2’-FL, which serves as food for the bacteria’s growth.
Both Yan and Acra emphasize that 2’-FL and its mechanisms described in the study are safe.
“We don’t yet have the adult human counterpart studies,” said Acra, “But the safety is well established, particularly in the infant model, where the immune system is less robust.”
“HMOs are safe – they should pose no danger to the body in a clinical trial for IBD therapy,” Yan said.
Yan’s team continues to study how 2’-FL protects the intestinal epithelial layer – both by stimulating bacterial metabolism and possibly by directly affecting epithelial cells. Their goal is to describe multiple functions and mechanisms of HMOs.
