Researchers have discovered a new mode of vertical transmission of microbiome from mother to infant, in which microbes in the mother’s gut shared genes with microbes in the infant’s gut during the perinatal period starting just before birth and extending into the first few weeks after birth. This horizontal gene transfer allowed maternal microbial strains to influence the functional capacity of the infant microbiome, in the absence of sustained transmission of the microbial strains themselves. Such a large-scale integrative analysis, presented on 22 December in the journal Cellprovides a series of high-resolution snapshots of intestinal colonization dynamics that influence infant development both before and after birth.
“This is the first study to describe the transfer of mobile genetic elements between maternal and infant microbiomes,” says senior study author Ramnik Xavier of the Broad Institute of MIT and Harvard. “Our study has also for the first time integrated gut microbiome and metabolomic profiles from both mothers and infants and discovered links between gut metabolites, bacteria and breast milk substrates. This investigation represents a unique perspective on the co-development of infant gut microbiomes and metabolomes under the influence of known maternal and dietary factors .”
Gut bacteria promote the maturation of the immune system in part through the production of microbial metabolites. The development of the infant’s gut microbiome follows predictable patterns, starting with the transfer of microbes from the mother at birth. In addition to maturation of the immune system, microbial metabolites also influence early cognitive development. The perinatal period represents a critical window for cognitive and immune system development, promoted by maternal and infant gut microbiota and their metabolites. Nevertheless, the co-evolution of microbiomes and metabolomes in the perinatal period and the determinants of this process are not well understood.
To address this knowledge gap, Xavier and colleagues tracked the co-evolution of microbiomes and metabolomes from late pregnancy to one year of age using longitudinal multiomics data from a cohort of 70 mother-infant dyads. They discovered large-scale mother-to-child transmission between species of mobile genetic elements, often involving genes associated with diet-related adaptations. Infant gut metabolomes were less diverse than maternal metabolomes, but contained hundreds of unique metabolites and microbe-metabolite associations not detected in mothers. Metabolomes and serum cytokine signatures of infants fed regular, but not extensively hydrolyzed, formula differed from exclusively breastfed infants.
“The infant’s gut contained thousands of unique metabolites, many of which were likely modified from breast milk substrates by gut bacteria,” says Tommi Vatanen, co-author on the study with Karolina Jabbar, both at the Broad Institute of MIT and Harvard. “Many of these metabolites likely affect the immune system and cognitive development.”
Pregnancy was associated with an increase in steroid compounds, including gonadal hormone derivatives and intermediates of bile acid biosynthesis, several of which were independently linked to impaired glucose tolerance. Although infant gut metabolomes were less diverse than maternal metabolomes, the researchers discovered more than 2,500 infants’ unique metabolomic characteristics. Moreover, they identified a number of infant-specific associations of bacterial species and faecal metabolites, including neurotransmitters and immunomodulators.
“We were surprised to find that maternal gut bacteria rarely observed in infants contributed to the infant’s gut microbiome structure,” says Xavier. exchange of mobile genetic elements between maternal and infant microbiomes.”
The authors say that the mother’s microbiome can shape the infant’s gut microbiome through horizontal gene transfer, apart from the classic vertical transfer of strains and species. Moreover, the identification of distinctive metabolomic profiles and microbe-metabolite interactions in the infant gut provides a platform for further studies of microbial contributions to infant development.
A study limitation was that the researchers did not assess changes in diet and lifestyle between pregnancy and the postpartum period, which may have influenced microbiome and metabolome changes. In future studies, they plan to further explore links between bacteria and metabolites and examine strain-specific bacterial metabolic production using isolated bacteria in vitro.
“Together, our integrative analysis extends the concept of vertical transmission of the gut microbiome and provides new insights into the development of maternal and infant microbiomes and metabolomes during late pregnancy and early life,” says Xavier.
This work was funded by the National Institutes of Health, the Juvenile Diabetes Research Foundation, the Center for Microbiome Informatics and Therapeutics, and the Wallenberg Foundations. Xavier is co-founder of Jnana Therapeutics and Celsius Therapeutics, Chairman of MoonLake Immunotherapeutics, and consultant for Nestlé; these organizations had no role in the study. All other authors declare no competing interests.
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