Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities
Open accessAbstract
Background: Persistent low-grade immune-inflammatory processes, oxidative and nitrosative stress (O&NS), and hypothalamic-pituitary-adrenal axis activation are integral to the pathophysiology of major depressive disorder (MDD). The microbiome, intestinal compositional changes, and resultant bacterial translocation add a new element to the bidirectional interactions of the gut-brain axis; new evidence implicates these pathways in the patho-aetiology of MDD. In addition, abnormalities in the gut-brain axis are associated with several chronic non-communicable disorders, which frequently co-occur in individuals with MDD, including but not limited to irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS), obesity, and type 2 diabetes mellitus (T2DM). Methods: We searched the PubMed/MEDLINE database up until May 1, 2016 for studies which investigated intestinal dysbiosis and bacterial translocation (the ‘leaky gut') in the pathophysiology of MDD and co-occurring somatic comorbidities with an emphasis on IBS, CFS, obesity, and T2DM. Results: The composition of the gut microbiota is influenced by several genetic and environmental factors (e.g. diet). Several lines of evidence indicate that gut-microbiota-diet interactions play a significant pathophysiological role in MDD and related medical comorbidities. Gut dysbiosis and the leaky gut may influence several pathways implicated in the biology of MDD, including but not limited to immune activation, O&NS, and neuroplasticity cascades. However, methodological inconsistencies and limitations limit comparisons across studies. Conclusions: Intestinal dysbiosis and the leaky gut may constitute a key pathophysiological link between MDD and its medical comorbidities. This emerging literature opens relevant preventative and therapeutic perspectives.
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The gut microbiome interacts with the brain primarily through three interacting pathways: neuronal, endocrine, and immunoregulatory.
“The gut microbiome has been shown to interact with the brain primarily through three interacting pathways, namely neuronal, endocrine, and immunoregulatory [12, 16].”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [16]
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References 205 · Cited by 278
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- Authors
- Slyepchenko, A., Maes, M., Jacka, F. N., Köhler, C. A., Barichello, T., McIntyre, R. S., Berk, M., Grande, I., Foster, J. A., Vieta, E., & Carvalho, A. F.
- Affiliations
- McMaster University (CA)
- Barwon Health (AU)
- Universidade Federal do Ceará (BR)
- The University of Texas Health Science Center at Houston (US)
- University Health Network (CA)
- Centro de Investigación Biomédica en Red de Salud Mental (ES)
- ORCID
- Venue
- Psychotherapy and Psychosomatics
- Publisher
- S. Karger AG
- Published
- 2016-11-25
- Volume
- 86
- Issue
- 1
- Pages
- 31-46
- ISSN
- 0033-3190 (ISSN-L)
- 1423-0348
- OpenAlex
- W2550547063
- Cited by
- 278
- References
- 205
- Citations by year
- 2026: 15 · 2025: 29 · 2024: 28 · 2023: 31 · 2022: 27 · 2021: 36 · 2020: 42 · 2019: 19 · 2018: 34 · 2017: 17
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Psychotherapy and Psychosomatics (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- Deakin Research Online (Deakin University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Stanley Medical Research Institute
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Centro de Investigación Biomédica en Red de Salud Mental
- Medical Research Council
- National Health and Medical Research Council (1059660)
- Instituto de Salud Carlos III (00012, JR15/00012)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- major depressive disorder, gut microbiota, gut dysbiosis, bacterial translocation, leaky gut, gut-brain axis, diet, irritable bowel syndrome, chronic fatigue syndrome, obesity, type 2 diabetes, immune activation, hypothalamic-pituitary-adrenal axis, neuroplasticity
- MeSH terms
- Gastrointestinal Microbiome, Major Depressive Disorder, Depressive Disorder, Major, Diabetes Mellitus, Type 2, Diet, Female, Humans, Inflammation, Male, Obesity, Fatigue Syndrome, Chronic, Comorbidity, Bacterial Translocation, Irritable Bowel Syndrome
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