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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.

Stimulant laxatives are well established as first- or second-line treatments for constipation and although they have a reliable therapeutic effect, alleged safety concerns still exist, particularly with long-term use. The potential harmful effects on the gastrointestinal system (including carcinogenicity) of the long-term use of diphenylmethane [bisacodyl, sodium picosulfate (SPS)] and senna stimulant laxatives were assessed in a comprehensive review of the publications identified in literature searches performed in PubMed and Embase up to and including June 2023. We identified and reviewed 43 publications of interest. While stimulant laxatives at supratherapeutic doses have been shown to cause structural alterations to surface absorptive cells in animals and humans, these effects are reversible and not considered clinically relevant. No formal long-term studies have demonstrated morphological changes in enteric neural elements or intestinal smooth muscle with bisacodyl or SPS in humans. Furthermore, there is no convincing evidence that stimulant laxatives are associated with the development of colon cancer, and in fact, chronic constipation itself has been reported to potentially increase the risk of colon cancer, therefore, the use of stimulant laxatives might reduce this risk. Many studies suggesting a possible harmful effect from laxatives were limited by their failure to consider confounding factors such as concomitant neurological disease, metabolic disorders, and age. These findings highlight the lack of evidence for the harmful effects of laxatives on the colon, and thus, the benefits of treatment with stimulant laxatives, even in the long-term, should be reconsidered for the management of patients with constipation. Plain language summary: Do stimulant laxatives damage the gut? Stimulant laxatives are widely used treatments for constipation that work by causing the muscles in the gut to contract and so move stool more effectively. Examples of these treatments include senna, bisacodyl and sodium picosulfate. Treatments such as these are typically available without a doctor's prescription and have a long history of helping people relieve their constipation. However, some concerns have been expressed about the safety of these treatments, particularly when they are used for a long time. We did a critical review of published studies of the safety of stimulant laxatives to try to find out whether there is any strong evidence for harm being caused by these treatments. We found 43 papers with information on the gut safety of stimulant laxatives. These studies looked at whether the treatments are associated with changes to gut structure or function and at whether there might be a link between these treatments and bowel cancer. Unfortunately, many of the studies were of poor quality. For instance, they did not look for things, in addition to the laxatives, that could have affected the results, such as the age of the patients, other medications they were taking or whether they had other health conditions that might have affected the bowel. Also, the populations in which the studies were done differed a lot, so they were hard to compare with one another. However, we did not find any strong evidence suggesting that stimulant laxatives damage the gut or cause cancer. We therefore concluded that the harms associated with stimulant laxatives are likely to have been overstated, and that patients should not be denied the benefits of stimulant laxatives for constipation, especially as they have been on the market for a very long time with no serious problems emerging. [ABSTRACT FROM AUTHOR]

Summary: Background: Gut‐directed hypnotherapy is effective for patients with irritable bowel syndrome (IBS). Despite its considerable evidence base, gut‐directed hypnotherapy is not widely available and remains a limited resource. This emphasises the need to select patients who are most likely to benefit. Aim: To determine whether baseline patient characteristics were predictive of response to gut‐directed hypnotherapy in patients with IBS Methods: We conducted a secondary analysis of outcomes of 448 patients with refractory Rome III IBS who participated in a randomised study confirming non‐inferiority of 6 compared to 12 sessions of gut‐directed hypnotherapy. We compared baseline patient characteristics, including age, sex, IBS subtype, quality of life and IBS‐Symptom Severity Scale (IBS‐SSS), non‐colonic symptom score and Hospital Anxiety and Depression (HAD) score between responders and non‐responders. We defined response as ≥50‐point decrease in IBS‐SSS or ≥30% reduction in pain severity scores. Results: Overall, 76.3% achieved ≥50‐point decrease in IBS‐SSS. Responders had a higher baseline non‐colonic symptom score (p = 0.005). Those who achieved ≥30% improvement in abdominal pain scores (59.8%) had higher baseline IBS‐SSS (p = 0.03), and lower baseline HAD‐depression score (p = 0.012). Fifty‐four patients (12%) dropped out of gut‐directed hypnotherapy. Compared to completers, dropouts had higher baseline HAD‐anxiety score (p = 0.034). Conclusions: These data suggest that patients with a higher burden of gastrointestinal and extraintestinal symptoms are most likely to benefit from gut‐specific behavioural intervention for refractory IBS. Clinical assessment of gastrointestinal, somatic and psychological symptom profiles may play a role in selecting patients for gut‐directed hypnotherapy. [ABSTRACT FROM AUTHOR]

Objective: Many studies have been published on disorders of the gut–brain interaction (DGBI) in Asia and Western Europe, but no previous study has directly assessed the difference between the two regions. The aim was to compare the prevalence of DGBI in Asia and Western Europe. Methods: We used data collected in a population‐based Internet survey, the Rome Foundation Global Epidemiology Study, from countries in Western Europe (Belgium, France, Germany, Netherlands, Italy, Spain, Sweden, and the United Kingdom) and Asia (China, Japan, South Korea, and Singapore). We assessed DGBI diagnoses (Rome IV Adult Diagnostic Questionnaire), anxiety/depression (Patient Health Questionnaire‐4, PHQ‐4), non‐GI somatic symptoms (PHQ‐12), and access to and personal costs of doctor visits. Results: The study included 9487 subjects in Asia and 16,314 in Western Europe. Overall, 38.0% had at least one DGBI; younger age, female sex, and higher scores on PHQ4 and PHQ12 were all associated with DGBI. The prevalence of having at least one DGBI was higher in Western Europe than in Asia (39.1% vs 36.1%, OR 1.14 [95% CI 1.08–1.20]). This difference was also observed for DGBI by anatomical regions, most prominently esophageal DGBI (OR 1.67 [1.48–1.88]). After adjustment, the difference in DGBI prevalence diminished and psychological (PHQ‐4) and non‐GI somatic symptoms (PHQ‐12) had the greatest effect on the odds ratio estimates. Conclusion: The prevalence of DGBI is generally higher in Western Europe compared to Asia. A considerable portion of the observed difference in prevalence rates seems to be explained by more severe psychological and non‐GI somatic symptoms in Western Europe. [ABSTRACT FROM AUTHOR]