Reconstruction characteristics of gut microbiota from patients with type 1 diabetes affect the phenotypic reproducibility of glucose metabolism in mice.

The human microbiota-associated (HMA) mice model, especially the germ-free (GF)-humanized mice, has been widely used to probe the causal relationships between gut microbiota and human diseases such as type 1 diabetes (T1D). However, most studies have not clarified the extent to which the reconstruction of the human donor microbiota in recipient mice correlates with corresponding phenotypic reproducibility. In this study, we transplanted fecal microbiota from five patients with T1D and four healthy people into GF mice, and microbiota from each donor were transplanted into 10 mice. Mice with similar microbiota structure to the donor exhibited better phenotypic reproducibility. The characteristics of the microbial community assembly of donors also influenced the phenotypic reproducibility in mice, and individuals with a higher proportion of stochastic processes showed more severe disorders. Microbes enriched in patients with T1D had a stronger colonization potential in mice with impaired glucose metabolism, and microbiota functional features related to T1D were better reproduced in these mice. This indicates that assembly traits and colonization efficacy of microbiota influence phenotypic reproducibility in GF-humanized mice. Our findings provide important insights for using HMA mice models to explore links between gut microbiota and human diseases.