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

transferred to the daughter bacterial cells upon cell division along with colonizing bacteria. Very little is
known about how common these two strategies are for MGE colonization. Nevertheless, they are likely to
have significant consequences for the infant gut microbiome assembly as they provide different fitness
benefits and create selection pressures on their host bacteria.

In the case of MGEs that use horizontal transfer to pass the colonization bottleneck, the fitness interests of
the original host and MGE are not aligned, as an MGE may survive by hitchhiking onto a different host. It
has been proposed that such relationships could be considered “selfish” or parasitic as the MGE would be
selected for better transmission at the expense of its host [27-29] . Specifically, polyvalent phages that infect a
range of bacterial taxa should be favored during the infant gut colonization, given the high and partly
stochastic bacterial turnover increases the benefit of their ability to infect multiple hosts [11,13,30] .
Consequently, horizontally transmitted MGEs could increase their own success in crossing the colonization
bottleneck. However, this success can be constrained by the fitness costs they impose on their hosts, as seen
[37]
[31]
with phages, which tend to spread after lysing their bacterial hosts .
If an MGE were to transfer vertically along with a bacterial host, we would expect to see co-selection where
the host and MGE lineages persist together when transmitted from mothers to infants [Figure 2]. This could
be enforced by “mutualistic” MGEs, which provide hosts with genes that improve their fitness [32-35] .
However, MGEs often create genetic baggage, incurring metabolic costs that render their hosts less fit than
the strains that do not carry MGEs [26,36] . Consequently, MGEs that primarily transfer vertically are expected
to incur low fitness costs and/or compensate for them by providing fitness-enhancing genes to their hosts.

While vertical and horizontal transmission are considered important drivers in the parasitism-mutualist
continuum, most MGEs likely fall between these two extremes with the ability to move horizontally or
vertically depending on environmental conditions [25,26] . Moreover, obligate lytic phages could transmit along
with their hosts when in pseudolysogeny, which is a poorly defined state where phages are temporarily
[31]
dormant in the infected bacterium . From this perspective, most MGEs can be seen as facultative
mutualists, capable of both vertical and horizontal transmission between bacteria during colonization,
which might be beneficial in highly dynamic and unpredictable environments such as the infant gut. We
will next present current evidence of how the colonization bottleneck could select three groups of MGEs
that are capable of vertical and horizontal transmission between bacterial cells: phages, conjugative
elements, and P-Ps [Figure 3].

A PORTION OF PHAGES, CONJUGATIVE ELEMENTS AND P-PS ARE MATERNALLY
INHERITED
Phages are bacterial viruses and the most abundant biological entity on earth . Most phages are either
obligately lytic or temperate. The lifestyle of obligately lytic phages involves infection of the host cell,
production of new viral particles, lysis of the host cell, and release of new viral progeny [Figure 3]. In
contrast, a temperate phage can additionally maintain its DNA integrated within its host’s genome as a
prophage and transmit vertically to daughter bacterial cells . Both phage types can move genetic material
[31]
horizontally between bacteria, facilitating the transfer of potentially beneficial accessory genes.

Overall, phage and bacterial mother-to-infant inheritance follow similar patterns. Specifically, infant phage
richness and diversity are lower compared to the maternal gut, and the infant gut phage turnover rate is
extremely high [25,38,39] , demonstrating how phages also pass the colonization bottleneck. In addition,
approximately 15%-30% of the infant bacteriophage community (phageome) is composed of phages from
the mother’s gut [40,41] . It is currently thought that most of these phages initially colonize the infant gut as