Amelioration of tic disorder by Jujuboside A via gut microbiota remodeling and intestinal 5-HT signaling

Background Tic disorder (TD) is a common chronic neuropsychiatric condition manifesting during childhood and adolescence. Jujuboside A (JuA) may alleviate TD symptoms; however, the mechanisms underlying its therapeutic effects remain unclear. Methods We established a rat model of TD and used histological techniques to evaluate the effects of JuA on pathological changes. We also measured 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels and assessed tryptophan hydroxylase 1 (TPH1) mRNA expression. Finally, we analyzed the gut microbiota composition in fecal samples using 16S rRNA metagenomic sequencing. Results JuA administration alleviated pathological changes in rats with TD, increased 5-HT and 5-HIAA levels, and upregulated TPH1 mRNA expression. Compared with no treatment, JuA treatment increased the proportion of Bacteroidia , Muribaculaceae , Bacteroidales , and Bacteroidota , while reducing that of Bacilli , Lactobacillaceae , Lactobacillus , Lactobacillales , and Firmicutes . Conclusion These findings indicate that JuA mitigates TD progression, potentially by remodeling the gut microbiota and regulating 5-HT levels.