August 10, 2022 5 min read
A review published in the journal of the American Society for Microbiology earlier this year outlines the efficacy of human milk oligosaccharide (HMO) supplementation in the inhibition of group B Streptococcus growth.
First characterized in human breast milk, HMOs are indigestible carbohydrates (i.e. prebiotics) that provide a food source for the nascent microbiome in the infant gut. In turn, the microbiome helps to shape the healthy development of the baby’s immune system and protects against infection.
Indeed, the HMOs present in breast milk help to prevent bacterial adhesion to the surface of the gut. It is well-established that HMOs are particularly adept at supporting the growth and colonization of Bifidobacteria in the gut.
In fact, the infant gut comprises up to 90% Bifidobacteria for this very reason. Emerging research also underscores the utility of HMO consumption in adults, with efficacy in ameliorating digestive issues, inflammatory bowel diseases, immune dysfunction, and chronic inflammation.
The type and abundance of HMOs present in a mother’s breast milk is dependent upon what forms of the galactoside 2-L-fucosyltransferase 2 (FUT2) and galactoside 2-L-fucosyltransferase 3 genes she possesses.
The FUT2 and FUT3 genes are required for the synthesis of the HMOs present in human breast milk. These genes encode enzymes that fuse specific carbohydrates to one another to create oligosaccharides.
Individuals with at least one functioning copy of FUT2 are referred to as secretors, whereas individuals lacking any functional copies of FUT2 are referred to as non-secretors. Non-secretor women are unable to synthesize and excrete HMOs including 2’-fucosyllactose (2’FL), 3’-fucosyllactose, and lactodifucotetraose into their breast milk and other bodily fluids.
Conversely, FUT3 status relates to an individual’s Lewis gene expression. The Lewis genes are related to the blood type antigen system, and functional FUT3 produces an enzyme needed to make Lewis antigen.
The Lewis antigen subsequently regulates the expression and activity of several other enzymes in mammary tissue that are responsible for making a distinct set of HMOs.
Thus, a functioning copy of FUT3 is essential for the secretion of Lewis antigen and several HMOs into breast milk and mucosa. Individuals lacking functional copies of FUT3 are referred to as Lewis-negative, whereas individuals with at least one functioning copy of FUT3 are known as Lewis-positive.
Group B Streptococcus (GBS) is a Gram-positive microbe that resides in both the colon and in the urogenital tracts of women, and is detected in around 30% of adults. Despite its prevalence, GBS is a major cause of death and illness in newborns who can be exposed to the pathogen during vaginal birth. GBS may also infect the uterus during pregnancy, which leads to prolonged exposure and increased risk of infection. In addition to disease in neonates, late-onset disease also occurs in a subset of infants between one week and three months after birth. Infected infants can present with conditions including meningitis, sepsis, and pneumonia and upwards of 4 million neonates will die globally each year as a result of complications from GBS infection.
In the United States and most other developed nations, the standard of care for prevention of GBS infection in newborns and the resulting complications is vaginal screening for GBS in pregnant women and prophylactic antibiotic administration before labor. However, this approach is problematic as antibiotics can result in the development of antibiotic resistant strains of GBS and other bacteria and does not protect against late-onset disease. Furthermore, antibiotics are damaging to both the maternal and infant microbiome, and can create dysbiosis and immune dysregulation in the newborn.
In a 2016 study, researchers took rectovaginal swabs, colostrum, and breast milk from a cohort of pregnant women, and nasopharyngeal and rectal swabs of their infants at birth, 6 days post-birth, and 2-3 months postpartum . The study showed that not only did Lewis-positive mothers have a significantly diminished likelihood of possessing GBS vaginally at the time of labor, but their children were also less likely to be colonized at birth. Furthermore, their infants had an increased ability to eliminate any GBS to which they were exposed within 3 months after birth. In vitro work conducted after observing these striking results revealed that lacto-N-difucohexaose I (LNDFHI) and other similar branched HMOs exerted the strongest inhibitory effects on GBS colonization. The branched HMOs, including LNDFHI, are present only in Lewis-positive individuals.
Following the 2016 study, many subsequent research endeavors were undertaken to understand the interaction of GBS and HMOs. The findings include growth inhibition of GBS by specific HMOs independent of the host immune system and modulation of GBS biofilm integrity. Thus, it is becoming increasingly clear that HMOs have the ability to disrupt GBS colony formation and growth and, in doing so, provide a benefit to at-risk populations like pregnant non-secretor women.
Most recently, an in vivo mouse model was used to study the effects of HMO treatment on vaginal GBS colonization . The researchers found that animals administered HMOs before or during infection with GBS exhibited drastically lower vaginal GBS content than control animals. This effect was achieved without modulating the overall composition of the vaginal microbiome. The HMOs used in this study were full spectrum in the form of lyophilized human breast milk from donors.
GBS infection is a major cause of morbidity and mortality in infants, and the current standard-of-care treatment of antibiotics can damage the nascent microbiome of the newborn and also promote the development of antibiotic resistant microbes. HMOs are prebiotic molecules unique to human breast milk and exhibit important benefits to newborns. Depending on the genetics of the mother, an infant may or may not have exposure to many of the HMOs that exert these beneficial effects, which include decreased incidence of GBS infection and an enhanced ability to clear GBS upon exposure. However, we do not currently recommend that Lewis-negative pregnant women consume HMO products at this time as clinical trials have yet to be conducted to confirm safety and efficacy.
Dr. Alexis Cowan, a Princeton-trained PhD specializing in the metabolic physiology of nutritional and exercise interventions.
Follow Dr. Cowan on Instagram: @dralexisjazmyn
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