Objective To analyze the effects of tryptophan (Trp) on the Trp-targeted metabolites and intestinal flora in mice with metabolic-associated fatty liver disease (MAFLD) based on Trp-targeted metabolomics and 16s rRNA high-throughput sequencing technology. Methods Male C57BL/6J mice aged 5-6 weeks were randomly divided into a control group (control, n=15) and an experimental group (n=30). The control group was fed a normal diet, while the experimental group was fed a high-fat diet (HFD) with a fat ratio of 60% to establish the MAFLD mouse model. The modeling time was 16 weeks. After the model was successfully constructed, the mice in the experimental group was randomly divided into the HFD group (n=10) and the Trp group (n=10). The HFD group was orally given the same amount of 0.9% normal saline, and the Trp group was given Trp at 50mg/ (kg·d). Both groups were intervened for 8 weeks. The body weight, food intake, liver wet weight, liver index, liver pathological changes, total cholesterol (TC), triglyceride (TG), and serum transaminase levels, as well as ileal pathology and mRNA expression levels of tight junction proteins were detected. The intestinal microbiota and serum metabolites were detected by 16s rRNA high-throughput sequencing and Trp-targeted metabolomics technology, and the association analysis between the differential microbiota and Trp-targeted metabolites was conducted through Spearman correlation analysis. Results Compared with the control group, the lipid deposition in the liver of mice in the HFD group increased significantly, and the body weight, liver wet weight and liver index increased significantly (P<0.01). Compared with the HFD group, the lipid deposition in the liver of mice in the Trp group was significantly reduced, and the body weight (P<0.01), liver wet weight (P<0.01), and liver index all decreased significantly (P<0.05). The mRNA expression of ileal tight junction proteins was up-regulated. The abundances of beneficial bacteria such as Lactobacillus and Allobaculum, as well as the diversity of intestinal flora were increased. Spearman correlation analysis showed that the level of the Trp metabolite 5-hydroxyindoleacetic acid (5-HIAA) was significantly negatively correlated with the abundance of Allobaculum (P<0.001). Conclusion Trp has an improving effect on MAFLD in mice, which is related to the enrichment of beneficial bacteria such as Lactobacillus, Allobaculum and the reduction of 5-HIAA production.
Key words
tryptophan /
metabolic associated fatty liver disease /
intestinal flora /
metabolomics
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