Faecal microbiota transplantation from patients with depression or healthy individuals into rats modulates mood-related behaviour

Knudsen, Julie Kristine; Michaelsen, Thomas Yssing; Bundgaard‐Nielsen, Caspar; Nielsen, René Ernst; Hjerrild, Simon; Leutscher, Peter; Wegener, Gregers; Sørensen, Susanne

doi:10.1038/s41598-021-01248-9

Cited by 53 publications

(40 citation statements)

References 70 publications

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“…Also in line with our findings Subdoligranulum and Coprococcus were consistently found to be depleted in individuals with generalized anxiety disorder and depression in several studies 28 . In a recent study Coproccocus was depleted in rats that exhibited depressed behavior upon fecal transplantation from depressed human subjects 29 , suggesting that Coproccocus may have a causal impact on depression. Both Subdoligranulum and Coprococcus are involved in the production of butyrate 26 and Subdoligranulum was found to be increased in omega 3 rich diet 30 .…”

Section: Discussionmentioning

confidence: 99%

Gut microbiome-wide association study of depressive symptoms

et al. 2022

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Depression is one of the most poorly understood diseases due to its elusive pathogenesis. There is an urgency to identify molecular and biological mechanisms underlying depression and the gut microbiome is a novel area of interest. Here we investigate the relation of fecal microbiome diversity and composition with depressive symptoms in 1,054 participants from the Rotterdam Study cohort and validate these findings in the Amsterdam HELIUS cohort in 1,539 subjects. We identify association of thirteen microbial taxa, including genera Eggerthella, Subdoligranulum, Coprococcus, Sellimonas, Lachnoclostridium, Hungatella, Ruminococcaceae (UCG002, UCG003 and UCG005), LachnospiraceaeUCG001, Eubacterium ventriosum and Ruminococcusgauvreauiigroup, and family Ruminococcaceae with depressive symptoms. These bacteria are known to be involved in the synthesis of glutamate, butyrate, serotonin and gamma amino butyric acid (GABA), which are key neurotransmitters for depression. Our study suggests that the gut microbiome composition may play a key role in depression.

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Section: Discussionmentioning

confidence: 99%

Gut microbiome-wide association study of depressive symptoms

et al. 2022

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“…Major depressive patients displayed gut dysbiosis like decreased diversity and richness of the gut microbiota compared to healthy subjects. − Several recent systematic and meta-analyses also observed differences in the commensal microbiota of patients with depression versus healthy volunteers . Fecal microbiota transplantation (FMT) from patients with depression into recipient rodents led to inherited anxiety- and depression-like phenotypes, anhedonia, and gut metabolite changes. − Germ-free mice inoculated with microbiota derived from patients with depression also exhibited depression-like behavior . Moreover, the bidirectional connection between the gut and brain has been endorsed with comorbidity between gastrointestinal and neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, and mood disorders. , Thus, changes in the gut microbiota–brain axis, which are readily impacted by environmental factors and stress, are anticipated in the pathogenesis of anxiety and depression …”

Section: Introductionmentioning

confidence: 99%

Multi-strain Probiotic Formulation Reverses Maternal Separation and Chronic Unpredictable Mild Stress-Generated Anxiety- and Depression-like Phenotypes by Modulating Gut Microbiome–Brain Activity in Rats

Dandekar

Palepu

Satti

et al. 2022

ACS Chem. Neurosci.

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Depression is a debilitating mental disorder that affects >322 million people worldwide. Despite the availability of several antidepressant agents, many patients remain treatment refractory. A growing literature study has indicated the role of gut microbiota in neuropsychiatric disorders. Herein, we examined the psychobiotic-like activity of multi-strain probiotic formulation in maternal separation (MS) and chronic unpredictable mild stress (CUMS) models of anxiety-and depression-like phenotypes in Sprague-Dawley rats. Early-and late-life stress was employed in both male and female rats by exposing them to MS and CUMS. The multi-strain probiotic formulation (Cognisol) containing Bacillus coagulans Unique IS-2, Lactobacillus plantarum UBLP-40, Lactobacillus rhamnosus UBLR-58, Bifidobacterium lactis UBBLa-70, Bifidobacterium breve UBBr-01, and Bifidobacterium infantis UBBI-01 at a total strength of 10 billion cfu along with L-glutamine was administered for 6 weeks via drinking water. Neurobehavioral assessment was done using the forced swim test (FST), sucrose preference test (SPT), elevated plus maze (EPM), and open field test (OFT). Animals were sacrificed after behavioral assessment, and blood, brain, and intestine samples were collected to analyze the levels of cytokines, metabolites, and neurotransmitters and histology. Animals exposed to stress showed increased passivity, consumed less sucrose solution, and minimally explored the open arms in the FST, SPT, and EPM, respectively. Administration of multi-strain probiotics along with L-glutamine for 6 weeks ameliorated the behavioral abnormalities. The locomotor activity of animals in the OFT and their body weight remained unchanged across the groups. Cognisol treatment reversed the decreased BDNF and serotonin levels and increased CRP, TNF-α, and dopamine levels in the hippocampus and/or frontal cortex. Administration of Cognisol also restored the plasma levels of L-tryptophan, L-kynurenine, kynurenic-acid, and 3hydroxyanthranilic acid; the Firmicutes-to-Bacteroides ratio; the levels of acetate, propionate, and butyrate in fecal samples; the villi/ crypt ratio; and the goblet cell count, which manifested in the restoration of intestinal functions. We suggest that the multi-strain probiotic and glutamine formulation (Cognisol) ameliorated the MS + UCMS-generated anxiety-and depression-like phenotypes by reshaping the gut microbiome−brain activity in both sexes.

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“…Depression, beyond our conventional appreciation of being a non-infectious neuropsychological disease, is transmissible through fecal microbiota transplantation (FMT) from depressed donors, either patients or animals, to recipient. Julie found that Flinders Resistant Line rats receiving FMT from MDD patients displayed significantly more depressive-like behaviors than those receiving FMT from healthy individuals ( 105 ). Moreover, intestine microbiota taxa were also transferred to recipients with the group receiving FMT from MDD patients carrying on certain taxa which was similar to their donors.…”

Section: The Microbiota-gut-brain Axis and Depressionmentioning

confidence: 99%

Recognizing the role of the vagus nerve in depression from microbiota-gut brain axis

Tan¹,

Yan

et al. 2022

Front. Neurol.

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Depression is a worldwide disease causing severe disability, morbidity, and mortality. Despite abundant studies, the precise mechanisms underlying the pathophysiology of depression remain elusive. Recently, cumulate research suggests that a disturbance of microbiota-gut-brain axis may play a vital role in the etiology of depression while correcting this disturbance could alleviate depression symptoms. The vagus nerve, linking brain and gut through its afferent and efferent branches, is a critical route in the bidirectional communication of this axis. Directly or indirectly, the vagus afferent fibers can sense and relay gut microbiota signals to the brain and induce brain disorders including depression. Also, brain changes in response to stress may result in gut hyperpermeability and inflammation mediating by the vagal efferents, which may be detrimental to depression. Notably, vagus nerve stimulation owns an anti-inflammatory effect and was proved for depression treatment. Nevertheless, depression was accompanied by a low vagal tone, which may derive from response to stress and contribute to pathogenesis of depression. In this review, we aim to explore the role of the vagus nerve in depression from the perspective of the microbiota-gut-brain axis, highlighting the relationship among the vagal tone, the gut hyperpermeability, inflammation, and depression.

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Faecal microbiota transplantation from patients with depression or healthy individuals into rats modulates mood-related behaviour

Cited by 53 publications

References 70 publications

Gut microbiome-wide association study of depressive symptoms

Gut microbiome-wide association study of depressive symptoms

Multi-strain Probiotic Formulation Reverses Maternal Separation and Chronic Unpredictable Mild Stress-Generated Anxiety- and Depression-like Phenotypes by Modulating Gut Microbiome–Brain Activity in Rats

Recognizing the role of the vagus nerve in depression from microbiota-gut brain axis

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