Piovezani Ramos Gabriela, Camilleri Michael
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
Dig Dis Sci. 2023 May;68(5):1677-1690. doi: 10.1007/s10620-022-07700-8. Epub 2022 Nov 14.
Irritable bowel syndrome with diarrhea and functional diarrhea are disorders of gut-brain interaction presenting with chronic diarrhea; they have significant impact on quality of life. The two conditions may exist as a continuum and their treatment may overlap. Response to first-line therapy with antispasmodics and anti-diarrheal agents is variable, leaving several patients with suboptimal symptom control and need for alternative therapeutic options. Our aim was to discuss current pharmacologic options and explore alternative therapeutic approaches and future perspectives for symptom management in irritable bowel syndrome with diarrhea and functional diarrhea. We conducted a search of PubMed, Cochrane, clinicaltrial.gov, major meeting abstracts for publications on current, alternative, and emerging drugs for irritable bowel syndrome with diarrhea and functional diarrhea. Currently approved therapeutic options for patients with first-line refractory irritable bowel syndrome with diarrhea and functional diarrhea include serotonin-3 receptor antagonists, eluxadoline and rifaximin. Despite their proven efficacy, cost and availability worldwide impact their utilization. One-third of patients with disorders of gut-brain interaction with diarrhea have bile acid diarrhea and may benefit from drugs targeting bile acid synthesis and excretion. Further understanding of underlying pathophysiology of irritable bowel syndrome with diarrhea and functional diarrhea related to bile acid metabolism, gastrointestinal transit, and microbiome has led to evaluation of novel therapeutic approaches, including fecal microbiota transplantation and enterobacterial "crapsules". These opportunities to treat disorders of gut-brain interaction with diarrhea should be followed with formal studies utilizing large samples of well-characterized patients at baseline and validated response outcomes as endpoints for regulatory approval.
腹泻型肠易激综合征和功能性腹泻是肠-脑互动失调导致的慢性腹泻疾病；它们对生活质量有重大影响。这两种病症可能连续存在，且治疗方式可能重叠。使用解痉药和止泻药进行一线治疗的效果不一，致使部分患者症状控制欠佳，需要其他治疗选择。我们的目的是讨论当前的药物选择，探索腹泻型肠易激综合征和功能性腹泻症状管理的替代治疗方法及未来前景。我们检索了PubMed、Cochrane、clinicaltrial.gov以及主要会议摘要，以查找有关腹泻型肠易激综合征和功能性腹泻的现有、替代及新兴药物的出版物。目前，对于一线治疗无效的腹泻型肠易激综合征和功能性腹泻患者，已批准的治疗选择包括5-羟色胺-3受体拮抗剂、埃卢多啉和利福昔明。尽管它们已被证实有效，但成本和全球可及性影响了其使用。三分之一的腹泻型肠-脑互动失调患者患有胆汁酸腹泻，可能会从针对胆汁酸合成和排泄的药物中获益。对腹泻型肠易激综合征和功能性腹泻与胆汁酸代谢、胃肠转运及微生物群相关的潜在病理生理学的进一步了解，促使人们评估了新的治疗方法，包括粪便微生物群移植和肠道细菌“胶囊”。这些治疗腹泻型肠-脑互动失调的机会，应通过使用大量基线特征明确的患者样本并以经过验证的反应结果作为监管批准终点的正式研究来跟进。
