Changes of gut microbiota and its effect on glucose tolerance in a novel mice model of insulin resistance (eLtaS trans) / 中华内分泌代谢杂志

ABSTRACT

Objective:To investigate the correlation between insulin resistance and alterations in gut microbiota using the animal model of insulin resistance(eLtaS transgenic mice).Methods:Glucose tolerance was measured in eLtaS trans mice and wild-type (WT) mice. Faecal samples of mice were collected for metagenomics and 16S rDNA sequencing. Alterations of gut microbiota in eLtaS trans mice were further analyzed. Faeces from eLtaS trans mice were transplanted into WT mice by " dirty cage" sharing experiment, and glucose tolerance of mice was measured at different time points after transplantation. Results:Significant differences in composition and function of gut microbiota were observed between eLtaS trans mice and WT mice( P=0.028). Compared with WT mice, the diversity of gut microbiota in eLtaS trans mice increased evidently, moreover the relative abundance of Phylum Firmicutes in eLtaS trans mice significantly increased( P<0.001). However, the relative abundance of Phylum Bacteroides and Phylum Verrucomicrobia decreased visibly( P=0.042, P=0.033). The relative abundance of Akkermansia muciniphila and Parabacterides distasonis related to metabolic diseases decreased significantly in eLtaS trans mice( P=0.033, P=0.013). The gut microbiota of eLtaS trans mice was clearly different from that of WT mice in carbohydrate metabolism, lipid metabolism, biosynthesis of other secondary metabolites, metabolism of other amino acids, energy production and transformation. The glucose tolerance of WT mice was impaired at 7th, 8th and 9th week after faecal transplantation, and recovered at 1 week after cessation of faecal transplantation. Conclusion:Insulin resistance leads to obvious changes of gut microbiota in mice, meanwhile the gut microbiota of insulin resistance mice can further induce impaired glucose tolerance.