Transcriptomic Insights into Biomechanical Modulation of Gastrointestinal Function in A Rat Model of Functional Dyspepsia.

Background: Functional dyspepsia (FD) is a common gastrointestinal disorder with multifactorial etiology involving impaired motility, mucosal barrier disruption, and inflammation. Non-pharmacological biotechnological interventions, such as external biomechanical modulation, have demonstrated therapeutic benefits; however, the underlying molecular mechanisms remain largely unexplored. Objectives: To investigate the transcriptomic and molecular changes induced by external biomechanical modulation in a rat model of FD and explore its potential as a physical biotechnological intervention for gastrointestinal dysfunction. Materials and Methods: Thirty-six male Wistar rats were randomly assigned to control, FD model, and biomechanical modulation intervention groups. FD was induced using a multifactorial approach (tail clamping stimulation + irregular diet + ice-cold saline gavage), and external biomechanical modulation was administered daily for one week. Gastrointestinal motility was assessed by measuring gastric emptying and intestinal propulsion rates. Duodenal tissues were analyzed using transcriptome sequencing, differential gene expression profiling, Gene Ontology (GO) annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Serum levels of TNF-α, IFN-γ, and IL-1β, as well as expression of tight junction proteins Occludin and ZO-1, were assessed via ELISA, immunofluorescence, and Western blotting. Results: FD rats exhibited reduced motility and villus atrophy, with elevated inflammatory cytokines and downregulated tight junction proteins. Transcriptomic profiling revealed significant gene expression changes in pathways related to digestion, nutrient absorption, immune modulation, and epithelial barrier integrity. KEGG analysis highlighted the involvement of PI3K-Akt signaling, neuroactive ligand-receptor interaction, and absorption-related pathways. PI3K-Akt pathway is an important pathway to regulate cell growth, proliferation and metabolism, and plays an important regulatory role in gastrointestinal motility disorders. External biomechanical modulation reversed these alterations, improving motility, reducing inflammation, and restoring mucosal integrity. Compared with the model group, the gastric emptying rate was significantly improved, and the small intestinal propulsion rate was increased by 9%. Conclusion: This study demonstrates that external biomechanical modulation exerts relevant effects on gastrointestinal function in FD through transcriptomic regulation of immune and barrier-related pathways. Further research should explore clinical applications and detailed mechanistic insights.