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

[88]

Figure 4. Range of mechanisms of how the MGE-encoded beneficial functions might help their host bacteria to cross the colonization
bottleneck. These functions include (A) aiding host metabolism and growth by encoding genes such as AMGs and CAZymes; (B)
antagonizing competitor bacteria by encoding type VI secretion systems and bacteriocins; (C) resisting antibiosis competition by
encoding ARGs, such as reuterin resistance genes [69] ; and (D) defending the host from parasitic MGEs through Inc types, superinfection
exclusion, and plasmid and phage defense systems. MGE: Mobile genetic element; AMGs: auxiliary metabolic genes; CAZymes:
carbohydrate-active enzymes; ARGs: antibiotic resistance genes.

phages and plasmids encode a wide range of hypothetical proteins with no known functions, which could
potentially provide important, novel functions to their hosts.

Besides aiding their hosts to increase their metabolic potential, MGEs could help their hosts colonize the
infant gut by antagonizing or protecting against competitor bacteria. Specifically, phages and conjugative
elements have been observed to carry bacteriocins and different types of growth-inhibiting genes which can
provide a competitive edge against other bacterial strains [34,79-84] [Figure 4B]. Such genes have been suggested
to be important for bacterial infant gut colonization [16,85] and may promote the transfer of MGEs, as in the
case of Pseudomonas aeruginosa phages in an insect model . Antibiotic resistance genes (ARGs) are
[86]
another example of well-known genes that provide defense against competitor bacteria [Figure 4C]. In
support of their importance, the infant gut harbors more ARGs compared to adults [48,87] , and these are
mostly carried by conjugative elements but not phages . Additionally, P-Ps carry ARGs more often than
phages, which indicates that they may contribute to the gut resistome . More research is hence needed to
[56]
explore if ARG carriage in MGEs provides a colonization benefit in the infant gut due to antibiotic usage or
competition between other bacteria.

Finally, the fitness costs of the increased MGE horizontal transfer during the induction spike could
constrain the prevalence of MGEs such as phages. Indeed, a few studies have proposed that the infant
phageome follows the kill-the-winner (KtW) or kill-the-competitor (KtC) population dynamics as a result
of selective phage predation targeting a subset of bacterial taxa [89,90] . Perhaps counterintuitively, various
phage types, such as cryptic prophages, have been shown to encode an enormous diversity of functional
phage defense genes that protect their bacterial hosts from both closely related and highly distinct
phages [91-97] . Several of these defense systems can also target plasmids [93,96] [Figure 4D]. Although many
defense systems seem to be exclusively encoded in phage genomes, Restriction-Modification (R-M), Toxin-