Evidence for horizontal gene transfer between human maternal microbiome and infant gut microbiome — ScienceDaily

Researchers have discovered a new mode of vertical microbiome transmission 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 immediately 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 persistent transmission of the microbial strains themselves. Such a large-scale integrative analysis, presented December 22 in the journal Cellprovides a series of high-resolution snapshots of gut colonization dynamics that affect infant development both before and after birth.

“This is the first study to describe the transfer of mobile genetic elements between the maternal and infant microbiomes,” said senior study author Ramnik Xavier of the Broad Institute of MIT and Harvard. “Our study also for the first time integrated gut microbiomes 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-evolution 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 gut microbiome follows predictable patterns, beginning with the transfer of microbes from the mother at birth. In addition to immune system maturation, microbial metabolites also affect early cognitive development. The perinatal period represents a critical window for cognitive and immune system development, promoted by the maternal and infant gut microbiota and their metabolites. Nevertheless, the co-evolution of microbiomes and metabolomes during the perinatal period and the determinants of this process are not well understood.

To address this knowledge gap, Xavier and his 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-infant transfer of mobile genetic elements between species, 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 in infants fed regular, but not extensively hydrolyzed, formula were different from exclusively breastfed infants.

“The infant gut harbored thousands of unique metabolites, many of which were likely modified from breast milk substrates by gut bacteria,” said Tommi Vatanen, co-author of 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 infant-unique metabolomic features. In addition, they identified many infant-specific associations of bacterial species and fecal metabolites, including neurotransmitters and immunomodulators.

“We were surprised to find that maternal gut bacteria that were rarely observed in infants contributed to the infant’s gut microbiome structure,” says Xavier. the 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, in addition to the classic vertical transfer of strains and species. Furthermore, the identification of distinct 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 consider changes in diet and lifestyle between pregnancy and the postpartum period, which may have affected microbiome and metabolome changes. In future studies, they plan to further explore connections 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 a co-founder of Jnana Therapeutics and Celsius Therapeutics, board member of MoonLake Immunotherapeutics and consultant to Nestlé; these organizations had no role in the study. All other authors declare no competing interests.

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