The impact of gut microbial dysbiosis on the atrophy of the hippocampus and abnormal metabolism of N-acetyl aspartate in type 2 diabetic rats.

ABSTRACT

Rationale and objectives: This study aimed to investigate the effect of intestinal dysbiosis on the hippocampal volume using proton magnetic resonance spectroscopy (1H-MRS) in a type 2 diabetes mellitus (T2DM) rat model. Materials and methods: We established a T2DM animal model with high-fat diet and streptozotocin (HFD/STZ) administration to Sprague-Dawley rats. Short-term ceftriaxone sodium administration was used to establish a T2DM intestinal dysbiosis (T2DM-ID) model. After establishing the model, fecal microbiota were detected using 16S rRNA sequencing. The models were then subjected to magnetic resonance imaging (MRI). Associations between MRI findings and fecal microbiota were evaluated. Results: Magnetic resonance imaging (MRI) showed that the bilateral hippocampal voxel value and N-acetylaspartate (NAA) level were lower in the experimental group than in the normal control (NC) group (p < 0.05) and that NAA/creatine in the left hippocampus was lower in the T2DM-ID group than in the NC group (p < 0.05). α and ß diversities differed significantly among the three groups (p < 0.05). In the T2DM and T2DM-ID groups, the abundance of bacteria in the phylum Proteobacteria increased significantly, whereas that of bacteria in the phylum Firmicutes decreased. The relative abundance of Actinobacteria was significantly increased in the T2DM-ID group. The Chao1 index (r = 0.33, p < 0.05) and relative abundance of Firmicutes (r = 0.48, p < 0.05) were positively correlated with the left hippocampal voxel, while the relative abundance of Proteobacteria was negatively correlated with the left hippocampal voxel (r = -0.44, p < 0.05). NAA levels, bilateral hippocampal voxels, and the relative abundance of Lactobacillus, Clostridia_UCG_014, and other genera were correlated positively (r = 0.34-0.70, p < 0.05). NAA levels and the relative abundances of Blautia and Enterococcus were correlated negatively (r = -0.32-0.44, p < 0.05). Conclusion: The T2DM-ID rat model showed hippocampal volume atrophy and decreased levels of neuronal markers (such as NAA). The abnormal content of specific gut microorganisms may be a key biomarker of T2DM-associated brain damage.