Department of Gastroenterology and Hepatology, Princess Alexandra Hospital Brisbane, and Translational Research Institute, University of Queensland, Brisbane, QLD, Australia.
Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK; Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK.
Lancet Gastroenterol Hepatol. 2016 Oct;1(2):133-146. doi: 10.1016/S2468-1253(16)30023-1. Epub 2016 Sep 8.
Traditionally, irritable bowel syndrome has been considered to be a disorder with no known underlying structural or biochemical explanation, but this concept is likely to be outdated. In this Review we challenge the widely accepted view that irritable bowel syndrome is an unexplained brain-gut disorder. There is epidemiological evidence that, in a major subset of patients, gastrointestinal symptoms arise first and only later do incident mood disorders occur. Additionally, possible mechanisms for gut-brain dysfunction have been identified, suggesting primary gut disturbances might be the underlying cause in a subgroup. Underlying mechanisms that could lead to irritable bowel syndrome include genetic factors (most notably an identified mutation of SCN5A); post-infectious changes, chronic infections and disturbances in the intestinal microbiota; low-grade mucosal inflammation, immune activation, and altered intestinal permeability; disordered bile salt metabolism (in 10-20% of cases with diarrhoea); abnormalities in serotonin metabolism; and alterations in brain function, which could be primary or secondary factors. Identical irritable bowel syndrome symptoms are probably due to different disease processes; grouping patients with this disorder into either diarrhoea-predominant or constipation-predominant subtypes promotes heterogeneity. An approach based on the underlying pathophysiology could help to develop therapies that target causes and ultimately provide a cure for patients with irritable bowel syndrome.
传统上，肠易激综合征被认为是一种没有已知潜在结构或生化解释的疾病，但这一概念可能已经过时。在这篇综述中，我们对肠易激综合征是一种无法解释的脑-肠疾病的广泛接受观点提出了挑战。有流行病学证据表明，在一大类患者中，胃肠道症状首先出现，只有在后来才会出现偶发性情绪障碍。此外，还发现了肠道-大脑功能障碍的可能机制，这表明在亚组中，原发性肠道紊乱可能是潜在的原因。可能导致肠易激综合征的潜在机制包括遗传因素（最显著的是 SCN5A 的一个已确定的突变）；感染后变化、慢性感染和肠道微生物群紊乱；低度黏膜炎症、免疫激活和肠道通透性改变；胆汁盐代谢紊乱（在腹泻的 10-20%病例中）；5-羟色胺代谢异常；以及大脑功能改变，这些可能是原发性或继发性因素。相同的肠易激综合征症状可能是由不同的疾病过程引起的；将患有这种疾病的患者分为腹泻为主型或便秘为主型亚组会增加异质性。基于潜在病理生理学的方法可以帮助开发针对病因的治疗方法，并最终为肠易激综合征患者提供治愈方法。
