The road to Rome IV and beyond: Evolution, refinements and future considerations for the Rome criteria for functional gastrointestinal disorders.

Evolution of the diagnostic criteria for functional gastrointestinal disorders (FGID) from Rome I to Rome IV in the past three decades represents a transformative shift from simplistic, symptom-based definitions to a nuanced framework that reflects the complex interplay between the gut and brain. Initial iterations, i.e. Rome-I and II criteria, established a standardized model that focused on clusters of symptoms rather than structural abnormalities, while Rome-III criteria introduced stricter symptom duration thresholds and acknowledged the influence of psychological factors. The introduction of Rome IV criteria in 2016 marked a watershed moment. FGIDs were renamed as 'disorders of gut-brain interaction' (DGBI), integrating advances in neurogastroenterology and emphasizing the pathophysiological roles of central neural processes, altered motility, immune regulation, dysbiosis, etc. These criteria redefined the diagnostic thresholds and emphasized on 'bothersome' symptoms that affect daily activities. For diagnosis of irritable bowel syndrome, abdominal pain, rather than discomfort, was essentially required and the sub-types of functional dyspepsia were more precisely defined. The Multidimensional Clinical Profile framework was added, which incorporated the sub-type, severity and psychological and physiological modifiers of DGBIs. However, the application of the Rome-IV criteria in the past eight years in clinical and research settings has faced a number of challenges, including the risk of underdiagnosing patients with milder symptoms, under-recognition of the overlaps of DGBIs and the lack of universal applicability due to socio-cultural and economic disparities in different geographical regions, Additionally, the new term, 'DGBI', while scientifically correct, can be discerned as potentially over-simplified and can itself be stigmatizing for patients who may inadvertently perceive these disorders as being primarily 'neuro-psychological'. The selective retention of the term 'functional' to name individual disorders such as functional dyspepsia and functional diarrhea remains to be justified. Advancements in neurogastroenterology research in the past decade have highlighted the significant prevalence of organic mimickers of DGBIs, most common being small intestinal bacterial overgrowth and non-celiac gluten sensitivity, which need to be ruled out, especially in 'refractory' DGBI cases. Substantial data on post-infectious DGBIs, especially post-COVID DGBIs, have been published. Importantly, multiple objective biomarkers have been proposed, which may complement and strengthen the symptom-based diagnostic criteria for DGBIs. By addressing the challenges, incorporating recent scientific advances and striking a balance between clinical practicality and global applicability, the future iterations of the Rome criteria have the potential to set new standards for the diagnosis and treatment of DGBIs.