Cross-Cohort Gut Microbiome Signatures of Irritable Bowel Syndrome Presentation and Treatment. Advanced science (Weinheim, Baden-Wurttemberg, Germany) Irritable bowel syndrome (IBS) is a prevalent disorder of gut-brain interaction without a reliable cure. Evidence suggests that an alteration of the gut microbiome may contribute to IBS pathogenesis, motivating the development of microbiome-targeted therapies to alleviate IBS symptoms. However, IBS-specific microbiome signatures are variable across cohorts. A total of 9204 datasets were meta-analyzed, derived from fourteen IBS microbiome discovery cohorts, three validation cohorts for diet-microbiome interactions, and five rifaximin therapy cohorts. The consistent bacterial species and functional signatures associated with IBS were identified. Network analysis revealed two distinct IBS-enriched microbiota clusters; obligate anaerobes that are found commonly in the gut, and facultative anaerobes typically present in the mouth, implying a possible association between oral bacterial translocation to gut and IBS pathogenesis. By analyzing diet-microbiome interactions, microbiota-targeted diets that can potentially modulate the altered gut microbiota of IBS subjects toward a healthy status were identified. Furthermore, rifaximin treatment of IBS subjects was linked with a reduction in the abundance of facultatively anaerobic pathobionts. Gut microbiome signatures were identified across IBS cohorts that may inform the development of therapies for microbiome modulation in IBS. The microbiota-targeted diet patterns described may enable nutritional intervention trials in IBS and for assisting dietary management. 10.1002/advs.202308313

Mast cell modulation: A novel therapeutic strategy for abdominal pain in irritable bowel syndrome. Cell reports. Medicine Irritable bowel syndrome (IBS) is one of the most prevalent gastrointestinal disorders characterized by recurrent abdominal pain and an altered defecation pattern. Chronic abdominal pain represents the hallmark IBS symptom and is reported to have the most bothersome impact on the patient's quality of life. Unfortunately, effective therapeutic strategies reducing abdominal pain are lacking, mainly attributed to a limited understanding of the contributing mechanisms. In the past few years, exciting new insights have pointed out that altered communication between gut immune cells and pain-sensing nerves acts as a hallmark driver of IBS-related abdominal pain. In this review, we aim to summarize our current knowledge on altered neuro-immune crosstalk as the main driver of altered pain signaling, with a specific focus on altered mast cell functioning herein, and highlight the relevance of targeting mast cell-mediated mechanisms as a novel therapeutic strategy for chronic abdominal pain in IBS patients. 10.1016/j.xcrm.2024.101780