Effects of Cinnamaldehyde on the Gut Microbiota Composition and Function in T1DM Model Mice

Objective To investigate the effects of cinnamaldehyde on the gut microbiota composition and function in T1DM model mice. Methods Following cinnamaldehyde intervention, total fecal DNA was extracted from experimental mice. The extracted DNA underwent quality assessment, library construction, sequencing, and bioinformatic analysis to obtain raw data. Subsequently, metagenomic analysis was performed: Kneaddata was used for quality control and host genome removal; MetaPhlAn2 was applied for taxonomic profiling, and HUMAnN2 for functional annotation. Strain-level resolution was achieved using StrainPhlAn based on MetaPhlAn2 results. Results Cinnamaldehyde intervention significantly increased Lactobacillus johnsonii abundance in healthy mice, rising to 43.56% and 38.88%. Additionally, Parasutterella excrementihominis, Dorea sp. 5_2, Burkholderiales bacterium 1_1_47, and Mucispirillum schaedleri showed marked enrichment in healthy mice. In T1DM model mice, intestinal Enterococcus faecalis, Lactobacillus reuteri, and Enterorhabdus caecimuris levels increased, while Lactobacillus murinus decreased. Conclusion At the functional level, multiple metabolism-associated genes were altered post-cinnamaldehyde treatment. Cinnamaldehyde modulated the expression of functional genes and metabolic pathway enrichment in murine microbiomes. Specifically, it promoted branched-chain amino acid (BCAA) synthesis and upregulated cell growth factor-related pathways in healthy mice, enhancing growth metabolism. In T1DM mice, cinnamaldehyde elevated TCA cycle-related genes, glycosaminoglycan synthesis, and signaling molecules (e.g., N-acetylneuraminic acid), facilitating host degradation and utilization of glucose/lipids. Correlation analyses revealed significant associations between blood glucose levels and 88 microbial gene functions/pathways (positive) and two pathways (negative); 11 pathways negatively correlated with insulin resistance.