Mapping the new frontier: Current perspectives on evolving gastrointestinal pathophysiology

With rapid advancement in cutting edge basic research in genetics, multi-omics, bioengineering and artificial intelligence focusing on improvement in precision medicine, the study of gastrointestinal (GI) pathophysiology has transitioned from describing GI conditions as isolated structural disorders to a systems-biology approach which recognize them as a complex network of interconnected systemic and functional diseases.It emphasizes the "interactome" -the complex crosstalk between the gut microbiome, the enteric nervous system, the mucosal immune system, and the enteroendocrine system -with associative effects on distant organs, metabolic, and immune function of the body.The gut is thus a central regulatory hub for metabolic health, immune education, and possibly neurocognitive function.Current perspectives emphasize three primary pillars in disease pathogenesis, namely the role of low-grade chronic inflammation and the integrity of the epithelial barrier (leaky gut), the metabolic influence of the microbiome, and its effect on functioning of distant organs.This narrative review will broaden the above perspectives highlighting the effect of smouldering inflammation affecting the epithelial barrier (its causative metabolomic signatures, the resulting epithelial plasticity, and its involvement in local and systemic diseases), the gut-microbiomedistant organ axis, the gut-metabolic axis (contributing to systemic inflammation and atherosclerosis), immuno-gastroenterology (related to GI cancers and other diseases), and advances in bioengineering (three dimensional in vitro modelling like organ-on-a-chip and personalized organoids) for better delineation of disease pathogenesis, biomarkers and precision therapeutics.Further, the utility of artificial intelligence in precision diagnostics (radiology, histology, multi-omics) and in shaping future therapies will be discussed as also the present limitations.