ArticleGastroenterology2025
Intestinal Epithelial Serotonin as a Novel Target for Treating Disorders of Gut-Brain Interaction and Mood.
Article in Gastroenterology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Intestinal Epithelial-Protective Effects ofJournal of microbiology and biotechnology · 2026Article
- A lesion-derived brain network of somatic symptoms for transdiagnostic individual application.BMC medicine · 2026Article
- Enteric and Sympathetic Nervous System Pathways Mediate Early Life Stress Effects on Gut Motility and Pain: Mechanistic Findings With Human Correlation.Gastroenterology · 2026Article
- Dup15q model mice exhibit impaired gastrointestinal motility and a constipation-like phenotype, alleviated by prucalopride.Translational psychiatry · 2026Article
- Optogenetic activation of liver-innervating vagal sensory neurons increases anxiety-like behavior in mice.Translational psychiatry · 2026Article
- MEKK3 bridges gut-brain communication and cerebral cavernous malformation pathogenesis.Cell death discovery · 2026Review
- A human-derived Bacteroides strain attenuates depressive-like behavior in a rat model of social defeat-induced stress.BMC medicine · 2026Article
- The Gut Microbiota-Tryptophan-Brain Axis in Autism Spectrum Disorder: A New Frontier for Probiotic Intervention.Microorganisms · 2026Review
- Mechanisms and clinical implications of gut-brain interactions.The Journal of clinical investigation · 2026Review
- The Intestinal Cues Promoting Serotonin Release From the Human Gut.Cellular and molecular gastroenterology and hepatology · 2026Article
- Mental health and gut-brain crosstalk: implications for depression and Alzheimer's disease.Neuroscience applied · 2026Review
- The Enteric Nervous System as a Mediator of Microbiota-Gut-Brain Interactions in Parkinson's Disease.Journal of neurochemistry · 2026Review
- The microbiota-tryptophan-brain axis in neurodegenerative diseases: pathogenic mechanisms, disease-specific roles, and translational therapeutics.Frontiers in microbiology · 2026Review
- A taxon-centered review of bacterial shifts in psychiatric disorders.Frontiers in psychiatry · 2026Review
- Microbial dysbiosis alters serotonin signaling in a postinflammatory murine model of visceral pain.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Enteric nervous system as a therapeutic target in gastrointestinal disorders.World journal of gastrointestinal pharmacology and therapeutics · 2025Article
- Central-peripheral neuroimmune dynamics in psychological stress and depression: insights from current research.Molecular psychiatry · 2025Review
- Supplementing HIV-ART with cannabinoids increases serotonin, BHB, and Ahr signaling while reducing secondary bile acids and acylcholines.Science advances · 2025Article
- SSRIs and depression: role of gut-brain communication.Nature reviews. Gastroenterology & hepatology · 2025Article
- Review
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Authors and funding
32 authors.
Funding
Abstract
BACKGROUND &
aimsMood disorders and disorders of gut-brain interaction (DGBI) are highly prevalent, commonly comorbid, and lack fully effective therapies. Although selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for these disorders, they may impart adverse effects, including anxiety, anhedonia, dysmotility, and, in children exposed in utero, an increased risk of cognitive, mood, and gastrointestinal disorders. SSRIs act systemically to block the serotonin reuptake transporter and enhance serotonergic signaling in the brain, intestinal epithelium, and enteric neurons. Yet, the compartments that mediate the therapeutic and adverse effects of SSRIs are unknown, as is whether gestational SSRI exposure directly contributes to human DGBI development.
methodsWe 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. We also conducted a prospective birth cohort study to assess effects of gestational SSRI exposure on DGBI development.
resultsSerotonin 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. Afferent vagal pathways were found to be conduits by which intestinal epithelial serotonin affects behavior. In utero SSRI exposure is a significant and specific risk factor for development of the DGBI, functional constipation, in the first year of life, irrespective of maternal depressive symptoms.
conclusionThese findings provide fundamental insights into how the gastrointestinal tract modulates emotional behaviors, reveal a novel gut-targeted therapeutic approach for mood modulation, and suggest a new link in humans between in utero SSRI exposure and DGBI development.
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