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Psychological comorbidity in gastrointestinal diseases: Update on the brain-gut-microbiome axis
Open accessAbstract
The high comorbidity of psychological disorders in both functional and organic gastrointestinal diseases suggests the intimate and complex link between the brain and the gut. Termed the brain-gut axis, this bidirectional communication between the central nervous system and enteric nervous system relies on immune, endocrine, neural, and metabolic pathways. There is increasing evidence that the gut microbiome is a key part of this system, and dysregulation of the brain-gut-microbiome axis (BGMA) has been implicated in disorders of brain-gut interaction, including irritable bowel syndrome, and in neuropsychiatric disorders, including depression, Alzheimer's disease, and autism spectrum disorder. Further, alterations in the gut microbiome have been implicated in the pathogenesis of organic gastrointestinal diseases, including inflammatory bowel disease. The BGMA is an attractive therapeutic target, as using prebiotics, probiotics, or postbiotics to modify the gut microbiome or mimic gut microbial signals could provide novel treatment options to address these debilitating diseases. However, despite significant advancements in our understanding of the BGMA, clinical data is lacking. In this article, we will review current understanding of the comorbidity of gastrointestinal diseases and psychological disorders. We will also review the current evidence supporting the key role of the BGMA in this pathology. Finally, we will discuss the clinical implications of the BGMA in the evaluation and management of psychological and gastrointestinal disorders.
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“Furthermore, gastrointestinal disorders such as IBD and IBS are frequently accompanied by persistent psychiatric comorbidities[6], [7], reinforcing the need for an integrated perspective in investigating these interconnected systems. [8].”
From The hidden genetic and microbial networks connecting neuropsychiatric and digestive disorders (2025) · cites this paper as [7]
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Metadata
- Authors
- Person, H., & Keefer, L.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Person, Hannibal
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2021-04
- Volume
- 107
- Pages
- 110209
- ISSN
- 0278-5846 (ISSN-L)
- PMC
- PMC8382262
- OpenAlex
- W3111424608
- Cited by
- 158
- References
- 229
- Citations by year
- 2026: 31 · 2025: 52 · 2024: 28 · 2023: 23 · 2022: 19 · 2021: 5
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (TL1TR001434)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- gut-brain axis, psychological comorbidity, gastrointestinal diseases, irritable bowel syndrome, depression, Alzheimer's disease, autism spectrum disorder, inflammatory bowel disease, enteric nervous system, prebiotics, probiotics, postbiotics, gut dysbiosis
- MeSH terms
- Gastrointestinal Microbiome, Brain-Gut Axis, Mental Disorders, Brain, Gastrointestinal Diseases, Humans, Comorbidity, Enteric Nervous System, Probiotics, Irritable Bowel Syndrome, Prebiotics
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