Current and Future Therapeutic Options for Irritable Bowel Syndrome with Diarrhea and Functional Diarrhea.

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.