Bioinformatic Identification of Shared Gene Networks Between Weaning-Induced Intestinal Inflammation and Neuroinflammatory-RelatedPathways

Introduction: Weaning is a critical developmental stage that can trigger intestinal inflammation through disruption of microbial homeostasis, immune responses, and epithelial barrier integrity. While numerous studies have explored gene expression changes during weaning in animals, no comparable analyses have been conducted in humans. Given the close physiological and genetic similarity between pigs and humans, piglet data were employed to investigate the molecular mechanisms underlying weaning-induced intestinal inflammation and its potential links to neurological pathways. Methods: A curated set of 117 differentially expressed genes related to gut inflammation was collected from bibliographic sources. Protein–protein interaction network analysis was performed using NetworkAnalyst and Cytoscape, followed by hub gene selection and functional enrichment using KOBAS, ClusterProfiler, and StringApp. Results: Among the identified hub genes, SOD1, CAT, TNF, CXCR4, TLR2, and TGFB1 play key roles in oxidative stress, immune response, glial regulation, and neuroinflammatory signaling. Enrichment analysis revealed significant associations with pathways such as Amyotrophic Lateral Sclerosis, TGF-β signaling, Folate and Vitamin B12 metabolism, and Inflammatory Bowel Disease, as well as biological processes like gliogenesis, hypoxia response, and cytokine signaling. Discussion: These findings suggest that intestinal inflammation during weaning may have systemic implications, highlighting shared molecular pathways relevant to neuroinflammatory-related processes. Conclusion: This study provides new insight into the genetic and molecular landscape of weaninginduced inflammation and its broader systemic effects. The identified shared molecular pathways may provide a foundation for future experimental studies investigating the broader biological implications of early-life intestinal inflammation.