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Page 2 of 14 Kreuze et al. Microbiome Res Rep 2025;4:7 https://dx.doi.org/10.20517/mrr.2024.51

INTRODUCTION
The human gut microbiota is a complex community of microorganisms, of which the most predominant
and most studied are the bacteria. In the infant gut, this microbiota is vital for infant healthy development
as it plays a part in immune system development, energy metabolism, and exclusion of pathogenic
[1-8]
microbes . Development of the microbiota starts at birth when the infants are first exposed to a wide
diversity of bacteria from their mothers and the surrounding environment [9,10] . This initial community goes
through a colonization bottleneck as the population starts at low diversity, with only a subset of bacterial
taxa from the mother being vertically inherited to the infant gut [11-13] [Figure 1]. Although the specific
ecological processes influencing this colonization event are not entirely understood, prior work suggests
that bacterial competition and environmental factors such as oxygen concentrations affect bacterial
colonization in infants [14-16] . While these advances are important in understanding the assembly of the infant
gut microbiota, the influence of mobile genetic elements (MGEs) carried by colonizing bacteria, including
plasmids and bacteriophages (phages for short) [17,18] , on infant gut microbiome development has been rarely

studied [19-21] .

In general, MGEs contribute to variable accessory genomes of bacteria and can drive horizontal gene
transfer and recombination between different bacterial strains at the population level . In the context of
[22]
crossing the colonization bottleneck, MGEs could help their bacterial hosts adapt and survive by encoding
fitness-enhancing genes. On the other hand, MGEs, especially phages, can be antagonistic to bacteria,
preventing the colonization of bacteria by lysing them. Furthermore, MGEs often have the potential to
move between different bacteria, which could create conflict between different MGEs within the same
bacterial cells.

In this perspective, we will first define and examine the colonization bottleneck in the context of infant gut
microbiome assembly, explaining how it might impact the vertical inheritance and subsequent colonization
of three types of maternal MGEs: phages, conjugative elements, and phage plasmids (P-Ps). We then
theorize how different MGEs affect their transmission dynamics and bacterial gene content and how they
interact with their host bacteria and other MGE within the infant microbiome. Finally, we highlight the
challenges of studying MGEs in gut microbiomes and suggest methodological tools and approaches to
tackle these complex interactions in the future.

INFANT GUT MICROBIOME ASSEMBLY IS AFFECTED BY EARLY COLONIZATION
BOTTLENECK
In ecology, a bottleneck is a loss in diversity caused by a large reduction in population size, as seen during
the microbial colonization of the infant gut. The low population size makes the infant gut subject to chance
events observed, such as when several bacterial strains are either vertically inherited at birth or acquired
later on [11,12] . However, the population is also subject to unique selection pressures of the infant gut. For
example, the relatively high oxygen concentration in the neonatal gut favors facultative anaerobes, such as
Escherichia coli and Enterococcus faecalis [14,23] . Additionally, the complex sugars unique to breast milk
(human milk oligosaccharides, HMOs) select for bacterial species that metabolize them, such as
[24]
Bifidobacterium longum subsp. infantis .
While MGEs are intimately dependent on their hosts for survival, an MGE can employ two different
lifestyles to colonize the infant gut: horizontal or vertical transfer between hosts [Figure 2]. In active
horizontal transfer through conjugation or lysis, the MGE may hitchhike on any bacteria successfully
passing the bottleneck. Alternatively, an MGE can rely on vertical transfer along with their bacterial
hosts [25,26] . This can be driven by co-selection, where MGEs that reside in bacterial cells are vertically