Urea, present in breast milk but not digested by the infant, appears to foster the growth of beneficial bacteria in the infant gut, suggests a study funded by the National Institutes of Health. Urea is a nitrogen-containing waste product of protein digestion. In return for the breast milk-supplied urea, the bacteria provide the infant with essential nutrients. The results have important implications for the development of infant formula.
The findings also add to a body of existing research showing that complex sugars present in breast milk, which the infant also cannot digest, promote colonization of beneficial bacteria in the infant digestive tract.
The study was conducted by David A. Sela, Ph.D., Xiaomeng You, and colleagues in Dr. Sela’s lab at the University of Massachusetts. It appears in Gut Microbes.
Microorganisms comprising the microbiome in the infant digestive track help tissue mature, participate in essential biochemical reactions, and foster the development of the immune system. Oligosaccharides—complex sugars in breast milk that the infant can’t digest—feed beneficial organisms in the microbiome and promote their spread. In turn, the beneficial organisms produce vitamins, nutrients, and compounds that foster the infant’s growth and development.
Previously, researchers found that Bifidobacterium infantis, a beneficial bacterium widespread in the infant microbiome, possessed enzymes that break down urea. Urea is produced in the liver and excreted in the urine. It is also widespread in breast milk.
For the current study, the researchers conducted a series of experiments to determine if Bifidobacterium infantis , adept at digesting human milk oligosaccharides, could also use the urea present in breast milk.
Lab cultures of Bifidobacterium infantis grew larger when supplemented with urea than cultures without it. The bacteria also produce urease, an enzyme that breaks down urea. The researchers also fed bacterial cultures urea labelled with a form of nitrogen that can be detected with the imaging technique, mass spectroscopy. Bacteria receiving the urea-labelled nitrogen incorporated it into many of its proteins, demonstrating that the bacteria were using the nitrogen released after urea was broken down. Moreover, Bifidobacterium infantisgiven urea produced more amino acids, including valine, leucine, and isoleucine, which are essential nutrients that their infant hosts cannot manufacture. Bacteria given urea also more readily attached to the surface of intestinal cells grown in culture. The researchers theorized that the ability to break down and use urea may help Bifidobacterium infantis colonize the lining of infant intestines.
The researchers believe their findings will contribute to later efforts to improve infant health. They added that the findings indicate that the composition of infant formula and other infant nutritional interventions may need to be evaluated for the amount of nitrogen they contain.
“If we have a better understanding of how the microbiome contributes to nutrition, we have a better understanding of how to provide nourishment to not only healthy infants but also infants who are preterm or are more predisposed to diseases, sickness, and other conditions that are deleterious to their health,” Dr. Sela said.
You, X., et al. Bifidobacterium longum subsp. infantis utilizes human milk urea to recycle nitrogen within the infant gut microbiome. Gut Microbes. 2023.