Summary: New research indicates that human milk oligosaccharides — the complex sugars unique to human breast milk — can change in pregnant women who take probiotic supplements.
Source: University of Rochester
New findings from the University of Rochester Medical Center suggest that the composition of human milk oligosaccharides (HMOs), long considered largely fixed, can be altered by maternal probiotic supplementation.
Published as a research letter in JAMA Pediatrics, the study challenges the prevailing view that HMOs are determined only by maternal genetics. HMOs are specialized sugar molecules found exclusively in human breast milk. Although infants cannot digest HMOs directly, these compounds serve as key substrates for specific members of the infant gut microbiome and play an important role in shaping early microbial communities. Because of these interactions, HMOs are thought to contribute to the reduced risk of certain infections and severe intestinal conditions, such as necrotizing enterocolitis, and may influence the development of immune-mediated conditions including food allergies.
“HMOs were thought to be genetically determined, almost like your blood type,” said Antti Seppo, Ph.D., research associate professor of Pediatric Allergy/Immunology at URMC and lead author of the letter. “But this data shows that HMOs can be modified by external factors.”
Lars Bode, Ph.D., associate professor of Pediatrics at the University of California San Diego and a co-author, emphasized the significance of the result. “We thought the interaction between HMOs and the microbiome was a one-way street, with HMOs shaping microbial communities by acting as prebiotics,” he said. “This is the first example suggesting that maternal dietary microbes, in the form of probiotics, can influence HMO composition.”
The investigation analyzed samples from 81 pregnant participants enrolled in a probiotic supplementation study conducted in Finland. Researchers measured and compared levels of 20 different HMOs in women who received probiotic supplements during pregnancy and those who did not. The study provides preliminary evidence that probiotic intake during pregnancy is associated with measurable changes in the profile of HMOs present in maternal milk.
The mechanisms by which probiotics may alter HMO composition are not yet fully understood. HMOs are synthesized in the mammary gland through the action of glycosyltransferase enzymes, and their patterns are influenced by maternal genetics—particularly Secretor and Lewis blood-group related enzymes (FUT2 and FUT3). Until now, aside from changes that occur naturally across lactation, few modifiable factors were linked to HMO variation. These new observations suggest that the maternal microbiome or dietary microbes could interact with host biology to affect how HMOs are produced.
Clinical and translational implications are potentially broad. Because specific HMO structures have been associated with protection against certain allergies and support of beneficial gut bacteria such as bifidobacteria, the ability to modulate HMO composition through probiotic use or diet could open new preventive strategies. “If particular HMO profiles lower the risk of food allergy or other immune conditions, then targeted manipulation of maternal HMOs might become a strategy to reduce disease risk in infants,” said Kirsi Järvinen-Seppo, M.D., Ph.D., chief of the Division of Pediatric Allergy/Immunology at URMC and senior co-author.
Future research directions include identifying which probiotic strains or combinations most strongly influence specific HMO structures, exploring dietary contributions to HMO variation, and testing whether deliberate modulation of HMOs during pregnancy or lactation translates into measurable health benefits for infants. Additional studies with larger, diverse populations and controlled interventions will be needed to confirm these initial findings and clarify causality.
Other co-authors on the study were Anna K. Kukkonen, M.D., Ph.D.; Mikael Kuitunen, M.D., Ph.D.; Erkki Savilahti, M.D., Ph.D.; and Chloe Yonemitsu, B.S.
Original research: Antti E. Seppo, PhD; Anna K. Kukkonen, MD, PhD; Mikael Kuitunen, MD, PhD; Erkki Savilahti, MD, PhD; Chloe Yonemitsu, BS; Lars Bode, PhD; and Kirsi M. Järvinen, MD, PhD. “Association of Maternal Probiotic Supplementation With Human Milk Oligosaccharide Composition.” JAMA Pediatrics. Published January 22, 2019. doi: 10.1001/jamapediatrics.2018.4835.
Association of Maternal Probiotic Supplementation With Human Milk Oligosaccharide Composition
Human milk oligosaccharides (HMOs) are complex glycans and the third-largest solid component in human milk. They are largely nondigestible to infants but serve as major substrates for the developing gut microbiota and influence maturation of the intestinal mucosal immune system. HMOs are synthesized from lactose by a series of glycosyltransferases; genetic variation in Secretor and Lewis genes (FUT2 and FUT3) contributes to differences in HMO structures between mothers. This heterogeneity means some breastfed infants are not exposed to certain HMO structures, which can influence microbiome development and disease risk. Previous work linked certain HMOs with protection against cow’s milk allergy and showed that HMO abundance changes during lactation, but no non-genetic modifiable factors had been firmly associated with HMO variation. This study evaluated whether maternal probiotic supplementation is associated with changes in HMO concentrations.