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Horizontal gene transfer shapes infant microbiome

A recent paper, published in the journal Cell, has shown how the maternal microbiome can influence the functional capacity of an infant’s gut microbiome without the vertical transfer of microbial strains themselves. The answer lies in horizontal gene transfer (HGT) – the transfer of genetic material between organisms that does not involve the transmission of DNA from parent to offspring.

“This is the first study to describe the transfer of mobile genetic elements between maternal and infant microbiomes,” said senior study author Ramnik Xavier of the Broad Institute of MIT and Harvard. Besides the HGT revelations, the study also found links between gut metabolites, bacteria, and breastmilk substrates, and offers further insight into how maternal and dietary factors influence the co-development of infant gut microbiomes.

Like mother, like daughter

What do we already know about the perinatal period and its influence on infant gut health? Well, we know that the maturation of our immune systems as infants is promoted by certain microbial metabolites. These metabolites are produced by the bacteria in our guts, which are transmitted to us from our mothers at birth.  What’s more, the metabolites produced by these bacteria also have an influence over our early cognitive development. However, a few crucial questions remain around what drives these processes in the gut.

To get a better understanding, Xavier and his team tracked the co-development of microbiomes and metabolomes in 70 mother-infant pairs, spanning late pregnancy to 1 year after birth. They did this by profiling the faecal microbiome and metabolome at different stages of pregnancy and infancy using deep metagenomics sequencing, untargeted faecal metabolite profiling, and assaying features such as circulating cytokines. They also implemented longitudinal sampling to investigate the vertical transmission of species, strains, and individual genes.

A picture of (gut) health

The result of this work was a number of high-resolution snapshots of gut colonization dynamics during infant development – both before and after birth (Figure 1). Using these snapshots, the team discovered that mobile genetic elements were transferred from mother to infant without any carrier strains being found in the infant gut.  

“We were surprised to find that maternal gut bacteria that were rarely observed in infants contributed to the infant gut microbiome structure,” said Xavier. “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.”

Figure 1: Multi-omic data from the mother-infant cohort. (A) Schematic illustration of metagenomic and metabolomic data. (B) t-distributed stochastic neighbour embedding (t-SNE) ordination of gut microbiome profiles based on Bray-Curtis dissimilarities of species-level abundances from metagenomic data.(C) t-SNE ordination of gut metabolite profiles based on log-scaled and Z score-normalized abundances of n = 858 metabolites annotated using reference standards.(D and E) Effects of factors on (D) species-level taxonomic composition and (E) metabolomic profiles in infants according to cross-sectional PERMANOVA analyses.

Besides functions related to mobile genetic elements, the 977 transmitted genes encoded functions related to carbohydrate utilization, amino acid metabolism, and iron acquisition and storage. Overall, maternal microbiomes were more diverse, but infants had lots of unique metabolites not detected in mothers (2500 infant-specific metabolomic features in total).

The team also discovered that formula-fed infants had a higher number of proinflammatory serum cytokines, which is consistent with previous research suggesting these infants have a higher risk of developing autoimmune disease.

Several limitations of the study mean that further work is needed to confirm some of these findings – for example, the team did not measure the influence of a changing diet on the results. However, this extensive multi-omics data does provide an insight into mother-to-infant HGT and its influence over the metabolic potential of the infant gut – including how this might impact immune system development.

More on these topics

Bacteria / Gut / Immune System / Microbiology / Microbiome