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Oligosaccharides in breast milk may help treat or prevent bacterial infections in newborns and adults.
Bacteria known as group B Streptococcus (GBS) are a common cause of blood infections, meningitis and stillbirth in newborns. Although GBS infections can often be treated or prevented with antibiotics, bacteria are becoming increasingly resistant. Today, researchers have found that human milk oligosaccharides (HMO) – short chains of sugar molecules abundant in breast milk – can help prevent GBS infections in human cells and tissues and in mice. . One day, HMOs could replace antibiotics to treat infections in infants and adults, they say.
The researchers will present their findings today at the American Chemical Society (ACS) fall meeting. ACS Fall 2021 is a hybrid meeting that will be held virtually and in person from August 22-26, and on-demand content will be available from August 30 to September 30. The meeting includes over 7,000 presentations on a wide range of scientific topics.
“Our laboratory has already shown that mixtures of HMOs isolated from the milk of several different donor mothers have antimicrobial and antibiofilm activity against GBS,” explains Rebecca Moore, who presented the work at the meeting. “We wanted to skip these in vitro studies to see if HMOs could prevent infections in cells and tissues of a pregnant woman and in pregnant mice.” Moore is a graduate student in the laboratories of Steven Townsend, Ph.D., at Vanderbilt University and Jennifer Gaddy, Ph.D., at Vanderbilt University Medical Center.
According to the United States Centers for Disease Control and Prevention, approximately 2,000 babies in the United States contract GBS each year, and 4 to 6% of them die from it. Bacteria are often transferred from mother to baby during labor and delivery. A pregnant woman with a positive GBS test usually receives intravenous antibiotics during labor to help prevent early-onset infections, which occur during the first week of life. Interestingly, the incidence of late infections (which occur one week to three months after birth) is higher in formula-fed infants than in breast-fed infants, suggesting that factors present in breast milk could help protect against GBS. If so, perhaps sugars could replace antibiotics which, in addition to killing beneficial bacteria, are becoming less effective due to the rise in antibiotic resistance.
Researchers studied the effects of combined HMOs from multiple mothers on GBS infection of placental immune cells (called macrophages) and the gestational membrane (the sac surrounding the fetus). “We found that HMOs were able to completely inhibit bacterial growth in both macrophages and membranes, so we very quickly turned to a mouse model,” says Moore. They investigated whether HMOs could prevent GBS infection from spreading into the reproductive tract of pregnant mice. “In five different parts of the reproductive system, we found a significant decrease in GBS infection with HMO treatment,” Moore notes.
To determine which HMOs and other oligosaccharides have these antimicrobial effects and why, the researchers set up an artificial two-species microbiome with GBS and the beneficial Salivary streptococcus species growing in a tissue culture plate, separated by a semi-permeable membrane. Next, the researchers added oligosaccharides commonly added to infant formulas, called galactooligosaccharides (GOS), which are derived from plants. In the absence of sugar, GBS suppressed the growth of “good” bacteria, but GOS helped this beneficial species to thrive. “We concluded that GBS produces lactic acid acid which inhibits growth, then when we add the oligosaccharide, the beneficial species can use it as a food source to overcome that suppression, ”says Moore.
Surprisingly enough, the first HMOs they tested in the system didn’t have this effect, but Townsend says it’s likely that one or more of the more than 200 unique sugars in breast milk will show activity. in the artificial microbiome test. The team intends to find out. According to the researchers, the reason HMOs can treat and prevent GBS infection is likely twofold: They act as an anti-stick by preventing pathogens from sticking to tissue surfaces and forming a biofilm, and they could act as a prebiotic by supporting growth. good bacteria.
“HMOs have been around as long as humans, and bacteria haven’t understood them. Presumably, this is because there is so much of it in milk, and it constantly changes during a baby’s development, ”Townsend says. “But if we could find out more about how they work, it’s possible that we could treat different types of infections with mixtures of HMOs, and maybe one day that could replace antibiotics in adults, as well as in babies. “
The researchers acknowledge the support and funding from the National Science Foundation.
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