Background and aims The functional gastrointestinal disorders (FGIDs) are extremely common conditions associated with a considerable personal, social and health economic burden. Managing FGIDs in clinical practice is challenging because of the uncertainty of symptom-based diagnosis, the high frequency of overlap between these conditions and the limited efficacy of available therapies. It has often been argued that successful drug development and management of FGIDs requires knowledge of the underlying pathophysiology. Numerous and highly variable candidate pathophysiological mechanisms have been implicated in the generation of FGID symptoms, but there is no current consensus on how to best define the relevance of these disturbances. Methods A group of international experts on FGIDs developed plausibility criteria that should be fulfilled by relevant pathophysiological mechanisms in FGIDs. Results Five criteria are proposed: (1) the presence of the abnormality in a subset of patients, (2) temporal association between proposed mechanism and symptom(s), (3) correlation between the level of impairment of the mechanism and symptom(s), (4) induction of the symptom(s) by provoking the pathophysiological abnormality in healthy subjects and (5) treatment response by a therapy specifically correcting the underlying disorder or congruent natural history of symptoms and dysfunction in the absence of specific therapy. Based on strength of evidence for these five criteria according to the Grading of Recommendations Assessment, Development and Evaluation system, a plausibility score can be calculated for each mechanism. Conclusion Evaluation of the strength of evidence for candidate pathophysiological abnormalities fulfilling these five plausibility criteria will help to identify the most relevant mechanisms to target for novel diagnostic approaches and for the development of new therapies.

中文翻译：

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功能性胃肠病病理生理机制的合理性标准：专家共识

背景和目标 功能性胃肠道疾病 (FGID) 是极其常见的疾病，与相当大的个人、社会和健康经济负担相关。由于基于症状的诊断的不确定性、这些条件之间的重叠频率高以及可用疗法的有效性有限，因此在临床实践中管理 FGID 具有挑战性。人们经常认为，成功的 FGID 药物开发和管理需要了解潜在的病理生理学。许多且高度可变的候选病理生理机制与 FGID 症状的产生有关，但目前尚未就如何最好地定义这些障碍的相关性达成共识。方法 一组 FGIDs 国际专家制定了 FGIDs 相关病理生理机制应满足的合理性标准。结果 提出了五个标准：(1) 一部分患者中存在异常，(2) 提出的机制与症状之间的时间关联，(3) 机制的损害程度与症状之间的相关性)，(4) 通过在健康受试者中引发病理生理学异常来诱导症状和 (5) 通过在没有特定治疗的情况下专门纠正潜在疾病或症状和功能障碍的一致自然病程的治疗的治疗反应。根据建议评估、制定和评估系统的分级，基于这五个标准的证据强度，可以为每种机制计算合理性分数。结论 评估满足这五个合理性标准的候选病理生理异常的证据强度将有助于确定最相关的机制，以针对新的诊断方法和新疗法的开发。