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Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat
Open accessAbstract
The gut microbiota interacts with the host via neuroimmune, neuroendocrine and neural pathways. These pathways are components of the brain-gut-microbiota axis and preclinical evidence suggests that the microbiota can recruit this bidirectional communication system to modulate brain development, function and behaviour. The pathophysiology of depression involves neuroimmune-neuroendocrine dysregulation. However, the extent to which changes in gut microbiota composition and function mediate the dysregulation of these pathways is unknown. Thirty four patients with major depression and 33 matched healthy controls were recruited. Cytokines, CRP, Salivary Cortisol and plasma Lipopolysaccharide binding protein were determined by ELISA. Plasma tryptophan and kynurenine were determined by HPLC. Fecal samples were collected for 16s rRNA sequencing. A Fecal Microbiota transplantation was prepared from a sub group of depressed patients and controls and transferred by oral gavage to a microbiota-deficient rat model. We demonstrate that depression is associated with decreased gut microbiota richness and diversity. Fecal microbiota transplantation from depressed patients to microbiota-depleted rats can induce behavioural and physiological features characteristic of depression in the recipient animals, including anhedonia and anxiety-like behaviours, as well as alterations in tryptophan metabolism. This suggests that the gut microbiota may play a causal role in the development of features of depression and may provide a tractable target in the treatment and prevention of this disorder.
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In the citing paper
“Both aging and stress weaken the integrity and function of the GI barrier (Kelly et al., 2016;Thevaranjan et al., 2017) and negatively affect BBB permeability (Esposito et al., 2002;Montagne et al., 2015) potentially accelerating inflammaging.”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Kelly et al., 2016
In the citing paper
“Such studies have found that various behavioral phenotypes can be transferred by FMT, including anxiety-like behavior and aspects of depressive symptomatology, suggesting that gut microbiota are key components of regulating anxiety and depression”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Kelly et al., 2016
In the citing paper
“Prior use of substances has been shown to increase the predisposition to depression; for example, adolescent cannabis consumption has been associated with increased risk of developing the disorder in early adulthood. 276”
From Time for united action on depression: a Lancet–World Psychiatric Association Commission (2022) · cites this paper as [276]
In the citing paper
“The authors observed that FMT from depressed individuals to microbiota-depleted rodents induced behavioral as well as physiological changes in the acceptors, i. e., the anxiety-like behavior, anhedonia and modifications in tryptophan biotransformation.”
From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [79]
In the citing paper
“It is widely accepted that the alteration of composition of bacterial communities in the gut caused by different stress have the potential to affect various metabolic pathways which may be involved in the development of depressive states [96,97].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [97]
In the citing paper
“However, in depressive patients without IBS symptoms, the Firmicutes/Bacteroidetes ratio was inversely correlated with the microbiota composition profiled in patients with IBS [145-147].”
From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [147]
In the citing paper
“Chronic or prolonged stress can lead to dysregulation of the HPA axis, which can have negative effects on various bodily systems, including the MGB axis (55).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [55]
In the citing paper
“although the nature of the dysbiosis in each of the studies varies, has not identified a consistent microbial biomarker, and causality between gut dysbiosis and clinical symptoms of depression has not been established.”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [62]
In the citing paper
“There have been a number of recent studies demonstrating that patients with MDD have an altered gut microbiome when compared to healthy controls [62, 63]”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [62]
In the citing paper
“These four studies all support that FMT from patients with depression to GF mice can result in depression-like behaviour in the recipient mice.”
From Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review (2020) · cites this paper as [34]
In the citing paper
“major depressive disorder in humans is associated with alterations of the gut microbiome,25”
From Food and mood: How do diet and nutrition affect mental wellbeing? (2020) · cites this paper as [25]
In the citing paper
“and transfer of faecal gut microbiota from humans with depression into rodents appears to induce animal behaviours that are hypothesised to indicate depression-like states.25 26”
From Food and mood: How do diet and nutrition affect mental wellbeing? (2020) · cites this paper as [25]
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Metadata
- Authors
- Kelly, J. R., Borre, Y., O' Brien, C., Patterson, E., El Aidy, S., Deane, J., Kennedy, P. J., Beers, S., Scott, K., Moloney, G., Hoban, A. E., Scott, L., Fitzgerald, P., Ross, P., Stanton, C., Clarke, G., Cryan, J. F., & Dinan, T. G.
- Affiliations
- University College Cork (IE)
- Teagasc - The Irish Agriculture and Food Development Authority (IE)
- Corresponding author
- Dinan, Timothy G.
- ORCID
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 82
- Pages
- 109-118
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W2292048640
- Cited by
- 1,683
- References
- 66
- Citations by year
- 2026: 130 · 2025: 189 · 2024: 222 · 2023: 212 · 2022: 207 · 2021: 222 · 2020: 191 · 2019: 144 · 2018: 96 · 2017: 58 · 2016: 11
- FWCI
- 53.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- Ulster University Research Portal (Ulster University) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Science Foundation Ireland (SFI/12/RC/, 12/RC/2273, 12/RC/, SFI/12/RC/2273.)
- APC Microbiome Institute (SFI/12/RC/2273)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- depression, gut microbiota, brain-gut-microbiota axis, fecal microbiota transplantation, anhedonia, anxiety-like behavior, tryptophan metabolism, kynurenine, neuroimmune dysregulation, neuroendocrine dysfunction, cytokines, salivary cortisol, lipopolysaccharide-binding protein, microbiome diversity
- MeSH terms
- Gastrointestinal Microbiome, Adult, Aged, Animals, C-Reactive Protein, Corticosterone, Depression, Disease Models, Animal, Feces, Female, Food Preferences, Humans, Hydrocortisone, Kynurenine, Lipopolysaccharides, Male, Middle Aged, RNA, Ribosomal, 16S, Case-Control Studies, Cytokines, Rats, Sprague-Dawley, Maze Learning, Gastrointestinal Tract, Rats
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