Host genotype is associated with selective colonization of human fecal microbiota in NCG and SGM3 mice: implications for microbiota-based therapies.

Humanized mouse models are widely used to investigate host-microbiota interactions, yet the extent to which host background contributes to engraftment fidelity remains incompletely defined. In this study, we transplanted fecal microbiota from healthy human donors into NCG and SGM3 mice and characterized engraftment using 16S rRNA sequencing. Both models exhibited reduced diversity relative to donors, but their colonization trajectories diverged. NCG recipients appeared closer to donors in β-diversity space, a pattern largely associated with the expansion of a limited set of opportunistic Proteobacteria such as Escherichia-Shigella and Citrobacter. In contrast, SGM3 mice displayed modestly higher α-diversity and retained a broader set of donor-associated genera, with selective enrichment of Bacillus, yet exhibited greater predicted functional divergence, with reductions in pathways related to ABC transport and carbohydrate metabolism. Several strictly anaerobic commensals, including Faecalibacterium, failed to colonize in either genotype. Collectively, these findings suggest that host genotype is associated with selective colonization of human fecal microbiota and support the utility of integrating compositional and functional criteria when selecting experimental models for translational microbiome research.