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Kreuze et al. Microbiome Res Rep 2025;4:7 https://dx.doi.org/10.20517/mrr.2024.51 Page 9 of 14

hitchers and other smaller MGEs that are incapable of transferring between bacterial cells.

CONCLUSIONS AND FUTURE PERSPECTIVES
In summary, there is currently a lack of evidence regarding the roles of MGE in infant gut bacterial
assembly and colonization. Understanding what MGEs are maternally inherited and the underlying
selection pressures and stochastic factors that affect MGE colonization are likely extremely important for
understanding the infant gut microbiome assembly. We hypothesize that the stressors involved in crossing
the colonization bottleneck are important drivers for MGE movement, which in turn is likely to affect the
phylogenetic and functional composition of the bacteriome. Specifically, the temperate phage induction
spike in infancy reflects the potential importance of horizontally transmitted MGEs in the infant gut. MGE-
encoded accessory genes might lead to co-selection with associated bacteria, while defense systems targeting
MGEs might limit their horizontal transmission and recombination. As more research is performed on viral
dark matter and undiscovered MGEs, we will start better understanding the potential role of MGEs as
resulting in a decrease in genetic and taxonomic diversity.
puppet masters behind infant gut microbiome assembly.

Future research should focus on developing more robust methodologies for identifying and characterizing
MGEs, especially novel P-Ps, in infant metagenomic datasets from diverse geographic regions. This is
important to accurately assess the prevalence, abundance, and genetic content of MGEs in different
populations. It would also be beneficial to collect more dense data, optimally with daily sampling, to
understand early in vivo MGE dynamics in the infant gut in higher resolution. Further bioinformatic and
experimental evidence into the functional roles of MGE-encoded genes in the infant gut, particularly those
involved in metabolism, antagonism, and MGE defense, is required. Additionally, controlled experiments
using multi-species synthetic bacterial communities and animal models could help elucidate the impact of
environmental stressors on MGE transmission dynamics and the relative fitness benefits and costs they may
impart to their hosts. Finally, expanding research to encompass a wider array of MGEs, including smaller
elements like “hitchers”, will provide a more comprehensive understanding of the infant gut mobilome and
its influence on microbial community assembly.

Glossary:
Vertical inheritance: The inheritance of microbes or MGEs from mother to child upon birth.
Vertical MGE transmission: The transmission of MGEs to the daughter cells of the same bacteria by cell
division.
Horizontal MGE transmission: The transmission of mobile MGEs between different bacterial cells
independent of cell division.
MGE/phage defense genes: Genes dedicated to interfering with the replication or maintenance of MGEs or
phages that have infected the cell.
Colonization bottleneck: A process that limits what microbes can colonize the infant gut microbiome,

Kill-the-winner (KtW) dynamics: A predator-prey type dynamic where phages control populations of the
most successful bacteria through lysis.
Kill-the-competitor (KtC) dynamics: A predator-prey type dynamic where phages protect their original host
bacteria by lysing competitive bacteria.
Core genome: The part of the bacterial genome that is conserved in all strains within the same taxa.
Accessory genome: The variable part of the bacterial genome that is not found in all strains within the same
taxon.