NEW YORK – The maternal impacts on the infant gut microbiome are not limited to microbes directly passed from a mother to her baby, but also include contributions by mobile genetic elements passed from maternal to infant bugs, according to new research by a Broad Institute-, Massachusetts Institute of Technology-, and Massachusetts General Hospital-led team.
"This investigation represents a unique perspective into the codevelopment of infant gut microbiomes and metabolomes under the influence of known maternal and dietary factors," senior and corresponding author Ramnik Xavier, a researcher affiliated with the Broad Institute, MIT, and Mass General Hospital said in a statement.
As they reported in Cell on Thursday, the researchers used metagenomic sequencing, liquid chromatography-mass spectrometry-based metabolomic profiling, and circulating cytokine assays to assess stool samples collected over more than a year — from time points at the end of pregnancy to a year after birth — in 137 mothers and 74 infants, including eight born by cesarean section.
The group included 70 mother-infant pairs, they noted, providing a microbe, microbial genes, and metabolite dynamics as infant gut microbiomes and immune systems developed.
"Taken together, our integrative analysis expands 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," Xavier explained, noting that the integrated microbiome and metabolite analyses highlighted "links between gut metabolites, bacteria, and breastmilk substrates."
In women reaching the end of pregnancy, for example, the team saw gut microbiome and metabolomic shifts that were distinct from those found around the time of delivery or at post-pregnancy time points, including higher-than-usual levels of Streptococcus salivarius and S. parasanguinis microbes that tend to make their way into infant gut microbial communities as well as changes expected to alter metabolism in mothers-to-be.
The researchers linked levels of species such as Bacteroides cellulosilyticus in the maternal gut microbiome — including bugs with relatively low maternal-to-infant transmission frequency — to specific functional and structural features in infant gut microbial communities over the first few months of life, including the presence of human milk oligosaccharide-degrading glycoside hydrolase enzymes.
Along with microbial genome sequences that turned up in both the maternal and infant metagenomic datasets, the investigators flagged 977 microbial genes from 11 microbial species that appeared to be passed from 22 of the mothers to their babies through horizontal gene transfer (HGT) between gut microbes without transmission of the original species.
"We were surprised to find that maternal gut bacteria that were rarely observed in infants contributed to the infant gut microbiome structure," Xavier said. "We also found evidence that prophages — dormant bacteriophages, or viruses that reside on bacterial genomes — contribute to the exchange of mobile genetic elements between maternal and infant microbiomes."
Although the infant gut was home to metabolites and species-metabolite combinations not found in corresponding maternal microbiomes, the team noted, the gut metabolites identified in infants remained less diverse overall relative to those found in their mothers.
The researchers also saw signs that the infant gut metabolome reflect their early diet, differing between breast-fed and formula-fed infants. Because these metabolomic features often tracked with immune cytokine signatures in blood serum samples, they speculated that the diet-related metabolite differences may also contribute to immune system maturation.
"The discovery that mother-to-infant interspecies HGT events shape infant microbial metabolic activities expands our understanding of maternal influences on the infant gut microbiome," the authors reported, noting that "identification of distinctive metabolomic profiles and microbe-metabolite interactions in the infant gut constitutes a platform for further study of microbial contributions to development."