Image of Group A Streptococcus (orange) taken using a scanning electron microscope during phagocytic interaction (blue). Credit: NIAID
Group B Streptococcus bacteria (GBS) is a common cause for blood infections, meningitis, and stillbirths in newborns. GBS infections can be prevented or treated with antibiotics. However, the bacteria is becoming more resistant. Researchers have now discovered that HMOs (human milk oligosaccharides) are short strings of sugar molecules found in breast milk. They can help prevent GBS infection in human cells, tissues, and mice. They believe HMOs could one day replace antibiotics in treating infections in infants or adults.
Today, the researchers will present their findings at the American Chemical Society's fall meeting.
Rebecca Moore will present the research at the meeting. She says that her lab has shown previously that HMOs derived from milk from several donor mothers have antimicrobial activity against GBS. We wanted to go beyond these in vitro studies and see if HMOs could prevent infection in cells and tissues of pregnant women and mice. Moore is a graduate student at Vanderbilt University Medical Center and Steven Townsend, Ph.D. at Vanderbilt University.
The U.S. Centers for Disease Control and Prevention estimates that approximately 2,000 babies are affected by GBS every year and that 4-6% of these babies die. During labor and delivery, the bacteria can be passed from mother to child. To prevent early-onset infections that occur within the first week of life, expectant mothers who test positive for GBS are usually administered intravenous antibiotics. Late-onset infections, which occur between one and three months after birth, are more common in infants who were breastfed than in those who were formula-fed. This suggests that breast milk may be able to protect against GBS. The sugars may be able to replace antibiotics that are less effective due to the increase in antibiotic resistance.
Researchers studied the effects of HMOs from multiple mothers on GBS infected placental immune cells (called macrophages), and the gestational membrane (the area surrounding the fetus). Moore says that HMOs could completely prevent bacterial growth in the macrophages as well as the membranes. Moore quickly switched to a mouse model. Moore and his colleagues looked into whether HMOs could stop a GBS outbreak from spreading to pregnant mice's reproductive tracts. Moore points out that HMO treatment significantly reduced GBS infections in five parts of the reproductive system.
Researchers created an artificial microbiome that contained GBS and Streptococcus salivarius species. The semi-permeable membrane separated them from the rest of the tissue culture plate. This was to determine which HMOs and other Oligosaccharides had these antimicrobial properties. Then, the researchers added oligosaccharides that are commonly added to infant formula, called galacto-oligosaccharides (GOS), which are derived from plants. GBS, which is devoid of sugar, suppressed growth of "good" bacteria. However, GOS allowed these beneficial species to grow. Moore explains that GBS produces lactic acid, which inhibits growth. The beneficial species can then use the oligosaccharide to counter this suppression.
Surprisingly, the HMOs that they tested first in the system didn't have this effect. Townsend believes it is possible that some of the more than 200 sugars found in human milk will be active in the artificial microbiome test. They plan to find out. Researchers believe there are two reasons HMOs can prevent and treat GBS infections. They act as an anti adhesive by preventing pathogens sticking to tissue surfaces, and form a biofilm. Additionally, they may act as prebiotics by encouraging the growth of good bacteria.
HMOs have existed for as long as human beings, and bacteria has not yet figured them. Townsend believes this is because there are so many HMOs in milk and that they change during a baby’s development. It's possible to treat various types of infections with HMOs. If we can learn more about their workings, we may be able to substitute antibiotics for adults and babies.
More information: Antimicrobial properties in human milk oligosaccharides of Group B Streptococcus. ACS Fall 2021.
