How a mother’s microbiome helps shape her baby’s development

During and after child birth, bacteria from the mother’s gut take up residence in the baby’s body, seeding a unique community of beneficial bacteria that will help break down food, synthesize vitamins, and help teach the baby’s nascent immune system to recognize foreign organisms.

A mother’s microbial gifts go even further than that, according to a new study from scientists at the Broad Institute of MIT and Harvard. They explored how the microbiomes of the mother and baby change during pregnancy and the first year of life, and discovered that some bacteria in the mother’s gut donate hundreds of genes to bacteria in the baby’s gut. These genes are involved in the development of the immune and cognitive systems and help the baby to digest a changing diet as it grows.

Appearing in Cell, the study is the first to uncover large-scale “horizontal gene transfer” events between different species of maternal and infant gut bacteria. The research also revealed a wide range of chemicals produced by the bacteria, or metabolites, that are unique to the baby. Together, the findings add to a growing appreciation for the complex physiological connection between mother and infant during early life.

“This study helps us better understand how the rich community of microbes in the gut initially forms and how it develops during infancy,” said Tommi Vatanen, a co-first author on the study who is now a researcher at the University of Helsinki. “The microbiome is very dynamic and develops along with other systems, so there’s a lot going on in the first years of life.”

“Our work presents a unique perspective of core development of the infant gut microbiome and metabolome under influence of the mother’s factors, with profound implications for immune and neurological development,” said senior author and Broad core institute member Ramnik Xavier, who is director of the Immunology Program, and co-director of the Infectious Disease and Microbiome Program at the Broad. Xavier is also the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School; director of the Center for Computational and Integrative Biology and Core member in the Department of Molecular Biology at Massachusetts General Hospital; and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.

A GUT’S REACTION

Xavier and his lab first began studying the microbiome at the Broad eight years ago. Since then, they have investigated how gut bacteria fluctuate during early life, how early microbiome colonization influences risk for immune-related diseases like type 1 diabetes, allergy, asthama ansd inflammatory bowel disease, and how the microbiome varies in different places around the globe.

In this new study, Xavier and his team aimed to more deeply explore the development of the microbiome during the first year of life. They sequenced bacterial DNA from stool samples from 70 mother-child pairs collected during late pregnancy through various stages of infancy.

In the infant gut bacterial genomes, the researchers pinpointed hundreds of genes that had originated in maternal bacteria. This indicates that the bacterial horizontal gene transfer from mother to baby isn’t a one-time event at childbirth, but an ongoing process throughout the baby’s first year of life.

Among the shared genes the team identified are many that encode proteins related to the infant diet, such as enzymes that break down complex sugars in breast milk. “There seems to be a clear benefit to this gene transfer, in that it provides important functions to the new bacterial species in the baby,” said Vatanen.

The donor bacterial strains can share their genes without colonizing the baby’s gut, so more work is needed to figure out where and when this gene transfer is occurring. In addition, the scientists acknowledge that the infant’s microbes might also be acquiring genes from other people in its daily life, such as the nonbirthing parent, siblings, or grandparents, so there may be even more horizontal gene transfer events than they’ve been able to capture so far.

THE MOTHER OF INVENTION

To better understand the biological functions of the changing microbiome in the mother and baby, the researchers also examined microbial metabolites — substances produced or converted by microbes that can have effects throughout the body — in collaboration with members of Broad’s Metabolomics Platform.

In the mothers during and after delivery, the researchers observed changes in their microbiome and metabolome that could potentially affect maternal metabolic health, such as an increase in steroid compounds that have been linked to impaired glucose tolerance.

The team also revealed microbiome and metabolome profiles in the infants that were distinct from and less diverse than those in their mothers, including hundreds of unique metabolites not seen in the mothers, such as neurotransmitters and immune modulators.

In the metabolomic profiles of young, breastfed infants, the scientists found substances known to boost inflammation in disease, suggesting that in very early life, the metabolites promote healthy maturation of the immune system. “In many ways, inflammatory markers can educate the immune system so that it’s better prepared to resist toxins or bad bacteria and shows more resilience when it’s perturbed,” said Xavier.

Co-first author Karolina Jabbar, a Broad visiting scientist and researcher at the University of Gothenburg, led part of the work examining the impact of differing diets on the infant microbiome. The metabolomic profiles of infants fed regular (not hydrolyzed) formula were distinct from those of breastfed babies, including metabolites that may contribute to risk for immune-related diseases such as type 1 diabetes and asthma.

Future work on microbiome development could one day lead to new ways of reducing disease risk by altering the bacterial gut community or supplementing with key metabolites. These insights could also help guide recommendations for infant feeding or care strategies that harness the power of the microbiome to influence human health.

“We’ve shown that the maternal microbiome plays an important role in seeding the infant microbiome, and that it’s not a one-time event, but a continuous process,” said Xavier. “This may be yet another benefit of prolonged bonding between mother and child, providing more chances for these beneficial gene transfer events to occur.”

This work was supported by funding from the National Institutes of Health, the Juvenile Diabetes Research Foundation, the Center for Microbiome Informatics and Therapeutics at MIT, and The Wallenberg Foundations.

Main image credits: (Clockwise from top left): Streptococcus (Credit: Tom Schmidt); microbial biofilm of mixed species, from human body (Credit: A. Earl, Broad Institute/MIT); Bacillus (Credit: Tom Schmidt); Malassezia lopophilis (Credit: J.H. Carr, CDC).

Paper cited: Vatanen T, Jabbar K, et al. Mobile genetic elements from the maternal microbiome shape infant gut microbial assembly and metabolism. Cell. (185)26:4921-36. December 2022. DOI: 10.1016/j.cell.2022.11.023.