Briefly noted: LY Hung et al. Gastroenterol 2025; 168: 754-768. Open Access! Intestinal Epithelial Serotonin as a Novel Target for Treating Disorders of Gut-Brain Interaction and Mood

This study used transgenic, surgical, and pharmacological approaches to study the effects of intestinal epithelial serotonin reuptake transporter or serotonin on mood and gastrointestinal function, as well as relevant communication pathways.

Key findings:

• Serotonin reuptake transporter ablation targeted to the intestinal epithelium promoted anxiolytic and antidepressive-like effects without causing adverse effects on the gastrointestinal tract or brain; conversely, epithelial serotonin synthesis inhibition increased anxiety and depression-like behaviors. 
• In utero SSRI exposure is a significant and specific risk factor for development of the DGBI, functional constipation, in the first year of life.

My take: While this lengthy article presents data mainly from mice studies, it further supports the likelihood that SSRI selective targeting of the gut epithelium may improve anxiety, depression and comorbid DGBI. Selective targeting of the GI tract would reduce adverse effects of these medications.

Related blog posts:

• Brave New World of Neuromodulators (2024) for Disorders of Brain-Gut Interaction
• “How to Approach a Patient with Difficult-to-Treat IBS”
• Gut-Brain Modulators for Functional GI Disorders: Irritable Bowel, Dyspepsia, Functional Heartburn, and Cyclic Vomiting Syndrome
• Use of Antidepressant Medications to Treat Recurrent Abdominal Pain
• Dr. Neha Santucci: Management of DGBIs in the Post-Pandemic Era (Part 1)
• Dr. Neha Santucci: Management of DGBIs in the Post-Pandemic Era (Part 2)
• Brave New World: Psychotropic Manipulation & Pediatric Functional GI Disorders (2014)