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Kleerebezem et al. Microbiome Res Rep 2024;3:46 https://dx.doi.org/10.20517/mrr.2024.48 Page 9 of 14

Figure 2. Competitive environmental fitness parameters that influence synbiotic mechanisms. (A) Exemplary prebiotic utilization
strategies by a co-administered probiotic; left side of the cell: extracellular hydrolysis of the oligo- or polymeric substrate (e.g., FOS or
inulin) with the subsequent import of released mono-saccharides or small oligosaccharides (i.e., sucrose and 1-kestose) that enter
intracellular metabolism, with partial release of the substrate into the environment as “public goods”; right side of the cell: direct import
of small oligosaccharides (e.g., tri- and tetra-saccharides in GOS) with subsequent intracellular hydrolysis and metabolization, i.e.,
“privatized goods”; (B) exemplary scenarios of endogenous microbiome members that can compete with the co-administered probiotic
for the utilization of the prebiotic substrates. These competing capacities may be redundantly present in multiple members of the
microbiome. Moreover, these redundant utilization pathways may have varying affinities and utilization rates for the prebiotic
substrates, indicated by variations in arrow thickness; (C) In addition to the microbiome’s redundancy in prebiotic utilization capacities,
their variable substrate affinities and utilization rates, the high relative abundance of competing microbes in comparison to the
introduced probiotic favors complementary synbiotic effects rather than synergistic synbiotic effects, especially when the prebiotic
substrate can readily be utilized by multiple members in the ecosystem and thus has poor species- or strain-specific selectivity.
Consequently, the competing capacity of the dominating members of the microbiome (blue, pink, and orange) prevents the utilization of
the prebiotic by, and the resulting growth stimulation of, the co-administered probiotic (green). FOS: Fructo-oligosaccharides; GOS:
galacto-oligosaccharides.

[8,9]
intestine of these infants for a period of at least several months . With such an administration regimen, the
FOS prebiotics are highly unlikely to modify the intestinal milieu for such an extended period, implying that
the engraftment observed is probably strongly related to the relatively empty niche of the GI tract of
newborns that the L. plantarum strain is introduced into, which may explain the strain’s capacity to
colonize and occupy this niche for an extended period. These arguments support the hypothesis that
administration of the L. plantarum strain alone (without the prebiotic FOS) would likely achieve similar
results. However, these studies did not include such a control group and, therefore, are unable to establish
the importance of FOS in this approach. Notably, experiments that employed the simultaneous
administration of L. plantarum Lp900 and inulin could enhance gastric survival (i.e., by 1-2 logs) but failed
[12]
to affect intestinal persistence over an extended period . Analogously, in vitro studies that stimulated
conditions of the gastrointestinal tract demonstrated that L. plantarum survival during gastric passage (i.e.,
the acidity barrier of the stomach) could be significantly enhanced by the presence of glucose during the
gastric transit (in concentrations as low as 0.05% w/w), but no such effect was achieved by the presence of