Transcriptomic insights into loperamide-induced gastric dysmotility: RNA-seq analysis of a mouse model

Background Loperamide, a μ-opioid receptor agonist that slows gastrointestinal transit, is widely used as an antidiarrheal agent and an experimental model of gastric dysmotility and functional dyspepsia (FD). However, transcriptomic alterations associated with loperamide-induced delayed gastric emptying remain poorly characterized. This study aimed to investigate gastric gene-expression profiles associated with loperamide-induced gastric dysmotility using RNA sequencing. Methods Male BALB/c mice were intraperitoneally injected with loperamide after 20 h of fasting. Delayed gastric emptying was assessed in one cohort, while gastric antrum tissues from a separate cohort were collected for RNA sequencing. Differentially expressed genes (DEGs) were identified using fold change ≥1.5 and false discovery rate (FDR) <0.01. Gene set enrichment analysis (GSEA) and pathway-network analysis were conducted to characterize biological pathways associated with loperamide treatment. Results Loperamide significantly delayed gastric emptying, as demonstrated by increased gastric retention of phenol red. Transcriptomic analysis identified 1,356 DEGs, including 553 upregulated and 803 downregulated genes. GSEA revealed enrichment of inflammatory response-related pathways among upregulated genes, whereas synaptic transmission- and calcium signaling-related pathways were predominantly downregulated. Representative genes involved in cholinergic signaling ( Chrm2 and Chrna9 ), glutamatergic signaling ( Grm7 ), and calcium-channel function ( Cacna1a ) showed reduced expression, while Il33 was increased. Conclusion This study provides transcriptomic insights into loperamide-induced gastric dysmotility. The findings suggest coordinated downregulation of genes associated with neuronal/synaptic signaling together with enrichment of inflammatory response-related transcriptional pathways in the gastric antrum, providing a molecular framework for this widely used experimental model.