Identification of potential therapeutic targets of fatty acids for inflammatory bowel diseases: An in silico approach

Abstract

Inflammatory bowel diseases (IBD) are chronic disorders of the gastrointestinal tract, often associated with long-term adverse effects from conventional therapies. Here we investigated the potential of a collection of odd- and even-chain fatty acids (FAs) as alternative therapeutic agents for IBD. IBD-associated genes were retrieved from DisGeNET and the Therapeutic Target Database, while the molecular structures of 14 odd-chain and 58 even-chain FAs were obtained from PubChem. ADME profiling was conducted using SwissADME, and target prediction was performed via SwissTargetPrediction and STITCH, followed by interaction network construction using Cytoscape. Gene ontology and KEGG pathway enrichment analyses were carried out using the DAVID bioinformatics tool. The analysis identified pristanic acid, stearic acid, oleic acid and its isomers, and eicosapentaenoic acid as potential candidates for IBD therapy. GO analysis revealed involvement in inflammatory responses and extracellular matrix disassembly, while KEGG pathway analysis indicated significant associations with the TNF, IL-17, HIF-1, and PI3K-Akt signaling pathways, all of which play crucial roles in IBD. These findings were further supported by molecular docking studies that showed strong interactions between the identified FAs and key proteins in these pathways. Overall, the results suggest that fatty acids may modulate signaling pathways relevant to IBD, though further in vitro and in vivo validation is required.