Brain–gut–microbiota axis in depression: A historical overview and future directions

Chang, Lijia; Wang, Yan; Hashimoto, Kenji

doi:10.1016/j.brainresbull.2022.02.004

Cited by 178 publications

(117 citation statements)

References 223 publications

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“…It is also of interest to examine whether pain might affect depression-like behaviors in CIA mice or ABX-treated mice after FMT from RA patients. Third, the recent studies demonstrated the role of subdiaphragmatic vagus nerve on the depression-like behaviors in ABX-treated mice after FMT of depression-related microbes [ 20 , 22 , 24 , 55 , 56 ]. Further study on the role of subdiaphragmatic vagus nerve on depression-like behaviors in rodents after FMT from RA patients is needed.…”

Section: Discussionmentioning

confidence: 99%

Fecal microbiota transplantation from patients with rheumatoid arthritis causes depression-like behaviors in mice through abnormal T cells activation

Zhang

Tang

et al. 2022

Transl Psychiatry

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Depression is common in patients with rheumatoid arthritis (RA); however, the precise mechanisms underlying a link between depression and RA remain unclear. Accumulating evidence suggests the role of gut–microbiota–brain axis in depression. In this study, we investigated whether collagen-induced arthritis (CIA) mice produce depression-like behaviors and abnormal composition of gut microbiota. Furthermore, we investigated whether fecal microbiota transplantation (FMT) from RA patients causes depression-like phenotypes in antibiotic cocktail (ABX)-treated mice. CIA mice displayed depression-like behaviors, increased blood levels of pro-inflammatory cytokine interleukin-6 (IL-6), decreased expression of synaptic proteins in the prefrontal cortex (PFC), and abnormal composition of gut microbiota. Furthermore, FMT from RA patients caused depression-like phenotypes, alterations of gut microbiota composition, increased levels of IL-6 and tumor necrosis factor-α (TNF-α), and downregulation of synaptic proteins in the PFC compared to FMT from healthy controls. There were correlations between relative abundance of microbiota and plasma cytokines, expression of synaptic proteins in the PFC or depression-like behaviors. Interestingly, FMT from RA patients induced T cells differentiation in Peyer’s patches and spleen. Reduced percentage of Treg cells with an increase of Th1/Th2 index was observed in the mice after FMT from RA patients. These findings suggest that CIA mice exhibit depression-like behaviors, systemic inflammation, and abnormal composition of gut microbiota, and that FMT from RA patients produces depression-like behaviors in ABX-treated mice via T cells differentiation. Therefore, abnormalities in gut microbiota in RA patients may contribute to depression via gut–microbiota–brain axis.

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Section: Discussionmentioning

confidence: 99%

Fecal microbiota transplantation from patients with rheumatoid arthritis causes depression-like behaviors in mice through abnormal T cells activation

Zhang

Tang

et al. 2022

Transl Psychiatry

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“…Accumulating evidence suggests that alterations in the gut microbiota and microbe-derived metabolites play a key role in the pathophysiology of depression via the brain–gut–microbiota axis ( 41 ). It was found that CUMS treatment induced changes in the β diversity of gut microbiota and up-regulation of plasma intestinal mucosal barrier markers, ET and DAO, resulting in depression-like behavioral changes, which also supports the theory that the brain-gut axis is associated with depression.…”

Section: Discussionmentioning

confidence: 99%

The Antidepressant Effect of Deoiled Sunflower Seeds on Chronic Unpredictable Mild Stress in Mice Through Regulation of Microbiota–Gut–Brain Axis

Cui

Zheng³

et al. 2022

Front. Nutr.

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ObjectivesSunflower seeds provide tryptophan-rich proteins with the potential to protect against depression. Tryptophan is a precursor of serotonin and a substrate for the production of indole derivatives by gut microbiota. This study aimed to investigate the association between the depression-alleviating effects of deoiled and dechlorogenic sunflower seeds (DSFS) and regulation of gut microbiota.Materials and MethodsMale C57BL/6J mice were fed a diet comprising a source of soy protein (normal and model control), DSFS or whey protein concentrate (positive control) for 7 weeks, and chronic stress-induced depression was induced.ResultsFeeding the DSFS diet prevented depression-like behaviors, intestinal barrier damage, elevated plasma corticosterone, and reduced hippocampal serotonin levels in mice. Meanwhile, Feeding the DSFS diet significantly altered the gut microbiota structure, characterized by elevated relative abundances of Ileibacterium valens, Ruminococcus flavefaciens, Clostridium scindens, and Olsenella massiliensis, which were inversely associated with depressive behaviors and markers of mucosal barrier damage. DSFS also altered the gut metabolite profile, prevented depression-induced gut L-tryptophan depletion, and upregulated its metabolite indoleacetaldehyde.ConclusionFeeding the DSFS diet prevented depression in mice by remodeling the gut microbiota and bacterial tryptophan metabolism.

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“…Studies have proposed that the common pathways of the MBG axis are the immune system, endocrine system, neurotransmitter, and HPA axis. The immune system is one of most common ways in the MGB axis [ 47 , 48 ]. IL-6 and IL-1β are pro-inflammatory factors while IL-10 reduces inflammatory response by downregulating IL-1 and TNF-α levels [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Heat-inactivated Lacticaseibacillus paracasei N1115 alleviates the damage due to brain function caused by long-term antibiotic cocktail exposure in mice

et al. 2022

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Critical development period of intestinal microbiota occurs concurrently with brain development, and their interaction is influenced by the microbiota–gut–brain axis. This study examined how antibiotics exposure affected gut microbiota and brain development and analyzed the possible benefits of heat-inactivated Lacticaseibacillus paracasei N1115 (N1115). Thirty neonatal male mice were randomly divided into three groups and treated with sterilized water (control), an antibiotic cocktail (Abx), or antibiotics plus heat-inactivated N1115 (Abx + N1115) for 84 days. We found that while the mRNA levels of GABAAα1, GABAb1, and glucocorticoid receptor (GR) in the hippocampus and brain-derived neurotrophic factor (BDNF), GABAAα1, GABAb1, and nerve growth factor (NGF) in the prefrontal cortex were higher, the mRNA levels of 5-HT1A were lower in the Abx group. The Abx + N1115 group had lower mRNA levels of GABAAα1, GABAb1, and GR in the hippocampus and BDNF, GABAb1, and NGF in the prefrontal cortex than the Abx group. The latency period was longer in the Morris water maze test while longer rest time was seen in tail suspension test in the Abx group than the control and Abx + N1115 groups. In the open field test, the moving time and distance of the Abx group were reduced. Further, the alpha-diversity indexes of the Abx and Abx + N1115 groups were significantly lower than the control. Further, long-term exposure to antibiotics disrupted the intestinal microbiota as evidenced by decreased Bacteroides, Firmicutes, and Lactobacillus, and increased Proteobacteria and Citrobacter. However, N1115 significantly decreased the abundance of Citrobacter when compared with those in the Abx group. These results indicate that antibiotics can substantially damage the intestinal microbiota and cognitive function, causing anxiety and depression, which can be alleviated by heat-inactivated N1115 via modulation of the microbiota–gut–brain axis.

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Brain–gut–microbiota axis in depression: A historical overview and future directions

Cited by 178 publications

References 223 publications

Fecal microbiota transplantation from patients with rheumatoid arthritis causes depression-like behaviors in mice through abnormal T cells activation

Fecal microbiota transplantation from patients with rheumatoid arthritis causes depression-like behaviors in mice through abnormal T cells activation

The Antidepressant Effect of Deoiled Sunflower Seeds on Chronic Unpredictable Mild Stress in Mice Through Regulation of Microbiota–Gut–Brain Axis

Heat-inactivated Lacticaseibacillus paracasei N1115 alleviates the damage due to brain function caused by long-term antibiotic cocktail exposure in mice

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