Sugars from human breast milk may help prevent and treat GBS infections
During the fall 2021 meeting of the American Chemical Society (ACS), researchers confirmed that human milk oligosaccharides (HMOs) can help prevent Group B Streptococcus (GBS) infections in human cells and tissues, as well as mice.
The results led researchers to suggest that these strings of sugar molecules may not only inhibit GBS growth but may also, when in coculture with commensal bacteria, allow HMOs to replace antibiotics in treatment of GBS and perhaps other multi-drug resistant infections.
It’s particularly timely news since GBS is exhibiting increased antibiotic resistance.1
Defining the Challenge
Group B Streptococcus are bacteria that live naturally and, in most cases, undetected in the body. About 25% of all healthy, adult women carry the bacteria—which can be passed from mother to baby during delivery. 2, 3
Not every baby born to a mother who carries GBS will become ill, although GBS is reportedly passed on to about 1 in every 2,000 babies in the United States, with 4 to 6% of these babies dying from GBS.
If a newborn develops early-onset GBS, the most common complications include sepsis, pneumonia, and meningitis. 2, 3
A two-step process helps prevent early-onset GBS disease in infants: test pregnant women for GBS bacteria prior to delivery and if positive, administer antibiotics during labor to women at increased risk of delivering a baby who may develop GBS disease. 4
As for late-onset GBS infections, striking between one week and three months after birth, the treatment is typically antibiotics administered intravenously to the infant.4
Whether early-onset or late-onset, GBS bacteria are becoming increasingly resistant to antibiotics.1
A ray of hope around this challenge might be in HMOs, defined as short strings of sugar molecules abundant in breast milk. In breastfed babies, this structurally and biologically diverse group of complex indigestible sugars act as prebiotics scientifically shown to positively affect the microbiome.
While the existence of HMOs is old news, their link to GBS is fairly recent—only rising to headline status after researchers confirmed that GBS occurrence is lower in breastfed infants than formula-fed babies. This suggests that breast milk might help protect against GBS.
Onward and Upward
Fast forward to the research presented at ASC Fall 2021, when attendees learned of new evidence that HMOs can help prevent GBS infections in human cells and tissues, as well as mice.
“Our lab has previously shown that mixtures of HMOs isolated from the milk of several different donor mothers have antimicrobial and antibiofilm activity against GBS,” said Rebecca Moore, PhD candidate in Chemical Biology at Vanderbilt University and the study’s co-presenter at ASC Fall 2021. “We wanted to jump from these in vitro studies to see whether HMOs could prevent infections in cells and tissues from a pregnant woman, and in pregnant mice.”
To take this leap forward, the researchers studied the effects of the combined HMOs from several donors on GBS infection on placental immune cells—called macrophages. They also investigated the effects of HMOs on the gestational membrane—which is the sac surrounding the fetus.
“We found that HMOs were able to completely inhibit bacterial growth in both the macrophages and the membranes, so we very quickly turned to looking at a mouse model,” Moore said.
Specific to the mice, the researchers examined whether HMOs could prevent a GBS infection from spreading through the reproductive tract of pregnant mice. “In five different parts of the reproductive tract, we saw significantly decreased GBS infection with HMO treatment,” Moore emphasized.
Sugar High
Taking human milk science to a higher level, the researchers set out to identify which of these sugar strings have antimicrobial effects and why. First, the researchers set up an artificial two-species microbiome with GBS and the beneficial Streptococcus salivarius species growing in a tissue culture plate, separated by a semi-permeable membrane. Then, the researchers added oligosaccharides that are commonly added to infant baby formula, called galacto-oligosaccharides (GOS), which are derived from plants. In the absence of the sugar, GBS suppressed the growth of the “good” bacteria, but GOS helped this beneficial species grow.
“We concluded that GBS is producing lactic acid that inhibits growth, and then when we add the oligosaccharide, the beneficial species can use it as a food source to overcome this suppression,” Dr. Moore explained.
Precisely how HMOs treat and prevent GBS infection remains unclear, although the researchers hypothesize that it’s likely a two-fold reason: HMOs act as an anti-adhesive by preventing pathogens from sticking to tissue surfaces and forming a biofilm; HMOs could act as a prebiotic by supporting the growth of good bacteria.
“HMOs have been around as long as humans have, and bacteria have not figured them out. Presumably, that’s because there are so many in milk, and they’re constantly changing during a baby’s development,” said Steven Townsend, PhD, Associate Professor of Organic Chemistry at Vanderbilt University and the lab director for the study. “But if we could learn more about how they work, it’s possible that we could treat different types of infections with mixtures of HMOs, and maybe one day this could be a substitute for antibiotics in adults, as well as babies.”
1. Hayes K, O’Halloran F, Cotter L. A review of antibiotic resistance in Group B Streptococcus: the story so far. Crit Rev Microbiol. 2020 May;46(3):253-269. doi: 10.1080/1040841X.2020.1758626. Epub 2020 May 2. PMID: 32363979.
2. Centers for Disease Control and Prevention. Group B Strep (GBS). Available from https://www.cdc.gov/groupbstrep/index.html
3. American Pregnancy Association. Group B Strep Infection: GBS. Available from https://americanpregnancy.org/healthy-pregnancy/pregnancy-complications/group-b-strep-infection/
4. Centers for Disease Control and Prevention. Preventing Group B Strep Disease in Newborns. Available from https://www.cdc.gov/groupbstrep/about/prevention.html