Background & Aims Gastroesophageal reflux disease (GERD) affects up to 30% of adults in Western populations and is increasing in prevalence. GERD is associated with lifestyle factors, particularly obesity and tobacco smoking, which also threatens the general health. GERD carries risk of several adverse outcomes and there is widespread use of potent acid-inhibitors which are associated with long-term adverse effects. The aim of this systematic review was to assess the role of lifestyle intervention in the treatment of GERD. Methods Literature searches were performed in PubMed (from 1946), EMBASE (from 1980), and the Cochrane Library (no start date) to October 1, 2014. Meta-analyses, systematic reviews, randomized clinical trials (RCTs) and prospective observational studies were included. Results Weight loss was followed by decreased time with esophageal acid exposure in two RCTs (from 5.6% to 3.7% and from 8.0% to 5.5%, respectively), and reduced reflux symptoms in prospective observational studies. Tobacco smoking cessation reduced reflux symptoms in normal weight individuals in a large prospective cohort study (odds ratio 5.67). In RCTs, late evening meals increased time with supine acid exposure compared to early meals (5.2% points change), and head of the bed elevation decreased time with supine acid exposure compared to a flat position (from 21% to 15%). Conclusions Weight loss and tobacco smoking cessation should be recommended to GERD patients who are obese and smoke, respectively. Avoiding late evening meals and head of the bed elevation is effective in nocturnal GERD.

Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS.