Involvement of the gut-brain axis in vascular depression via tryptophan metabolism: A benefit of short chain fatty acids

Xiao, Weiping; Gao, Xinjie; Yang, Hongbin; Su, Jiabin; Weng, Ruiyuan; Gao, Ying; Ni, Wei; Gu, Yuxiang

doi:10.1016/j.expneurol.2022.114225

Cited by 13 publications

(7 citation statements)

References 94 publications

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“…68 Recent studies also documented the regulatory role of SCFAs in tryptophan and kynurenine metabolism in depression. 69,70 Similarly, ingesting a high-fiber-rich diet erases depressive symptoms in humans by modulating the production of SCFAs and tryptophan metabolism. 71 We also noted the decreased levels of kynurenic acid in the plasma of TRD and TRD-FMT animals, which were recovered following SCFAs treatment.…”

Section: Acs Chemical Neurosciencementioning

confidence: 99%

SCFAs Supplementation Rescues Anxiety- and Depression-like Phenotypes Generated by Fecal Engraftment of Treatment-Resistant Depression Rats

Palepu,

Gajula,

et al. 2024

ACS Chem. Neurosci.

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Alteration of gut microbiota and microbial metabolites such as shortchain fatty acids (SCFAs) coexisted with stress-generated brain disorders, including depression. Herein, we investigated the effect of SCFAs in a treatment-resistant depression (TRD) model of rat. Rats were exposed to chronic-unpredictable mild stress (CUMS) and repeated adrenocorticotropic hormone (ACTH) injections to generate a TRD-like phenotype. The cecal contents of these animals were engrafted into healthy-recipient rats and allowed to colonize for 4 weeks (TRD-FMT group). Blood, brain, colon, fecal, and cecal samples were collected for molecular studies. Rats exposed to CUMS + ACTH showed TRD-like phenotypes in sucrose-preference (SPT), forced swim (FST), and elevated plus maze (EPM) tests. The TRD-FMT group also exhibited anxiety-and depression-like behaviors. Administration of SCFAs (acetate, propionate, and butyrate at 67.5, 25, and 40 mM, respectively) for 7 days exerted robust antidepressant and antianxiety effects by restoring the levels of SCFAs in plasma and fecal samples, and proinflammatory cytokines (TNF-α and IL-6), serotonin, GABA, norepinephrine, and dopamine in the hippocampus and/or frontal cortex of TRD and TRD-FMT animals. SCFAs treatment elevated the expression of free-fatty acid receptors 2/3, BDNF, doublecortin, and zonula-occludens, and reduced the elevated plasma levels of kynurenine and quinolinic acid and increased mucus-producing goblet cells in TRD and TRD-FMT animals. In 16S sequencing results, decreased microbial diversity in TRD rats corresponds with differences in the genus of Faecalibacterium,

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Section: Acs Chemical Neurosciencementioning

confidence: 99%

SCFAs Supplementation Rescues Anxiety- and Depression-like Phenotypes Generated by Fecal Engraftment of Treatment-Resistant Depression Rats

Palepu,

Gajula,

et al. 2024

ACS Chem. Neurosci.

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Section: Effect Of Gut Microbiota-derived Scfas On Depressionmentioning

confidence: 99%

“…94 Rats with depressive-like behaviours exhibit a decreased relative abundance of SCFA-producing gut microbes and reduced serum levels of SCFAs, which are closely associated with cytokine expression and inflammatory pathway activation in neuroinflammation. 95 The levels of cytokines in the blood, including interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α), are significantly higher in patients with depression than General Psychiatry in healthy controls. 96 These pro-inflammatory cytokines, particularly IL-6, IL-1β and TNF-α, promote the generation of T helper 17 (Th17) cells, which are strongly implicated in depression and other CNS diseases.…”

Section: Scfas and Neuroinflammationmentioning

confidence: 99%

Gut microbiota-derived short-chain fatty acids and depression: deep insight into biological mechanisms and potential applications

Cheng,

Hu,

et al. 2024

Gen Psych

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The gut microbiota is a complex and dynamic ecosystem known as the ‘second brain’. Composing the microbiota-gut-brain axis, the gut microbiota and its metabolites regulate the central nervous system through neural, endocrine and immune pathways to ensure the normal functioning of the organism, tuning individuals’ health and disease status. Short-chain fatty acids (SCFAs), the main bioactive metabolites of the gut microbiota, are involved in several neuropsychiatric disorders, including depression. SCFAs have essential effects on each component of the microbiota-gut-brain axis in depression. In the present review, the roles of major SCFAs (acetate, propionate and butyrate) in the pathophysiology of depression are summarised with respect to chronic cerebral hypoperfusion, neuroinflammation, host epigenome and neuroendocrine alterations. Concluding remarks on the biological mechanisms related to gut microbiota will hopefully address the clinical value of microbiota-related treatments for depression.

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“…A forced swim test was performed according to the method previously described [23]. Brie y, the mice were placed into plastic buckets, each 18 cm in diameter and 25 cm in height and lled with water, and maintained at 23°C.…”

Section: Forced Swim Testmentioning

confidence: 99%

Supraphysiologic doses of 17β-Estradiol aggravate depression-like behaviors in ovariectomized mice possibly via regulating microglial responses and brain glycerophospholipid metabolism

Zhang

Chen

et al. 2023

Preprint

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Background 17β-Estradiol (E2) is generally considered neuroprotective in humans. However, the current clinical use of estrogen replacement therapy (ERT) is based on the physiological dose of E2 to treat menopausal syndrome and has limited therapeutic efficacy. The efficacy and potential toxicity of superphysiological doses of ERT for menopausal neurodegeneration are unknown. Methods In this study, we investigated the effect of E2 with a supraphysiologic dose (0.5 mg/kg, sE2) on the treatment of menopausal mouse models established by ovariectomy. We performed the open field, Y-maze spontaneous alternation, forced swim tests, and sucrose preference test to investigate behavioral alterations. Subsequently, the status of microglia and neurons was detected by immunohistochemistry, HE staining, and Nissl staining, respectively. Real-time PCR was used to detect neuroinflammatory cytokines in the hippocampus and cerebral cortex. Using mass spectrometry proteomics platform and LC-MS/ MS-based metabolomics platform, proteins and metabolites in brain tissues were extracted and analyzed. BV2 and HT22 cell lines and primary neurons and microglia were used to explore the underlying molecular mechanisms in vitro. Results sE2 aggravated depression-like behavior in ovariectomized mice, caused microglia response, and increased proinflammatory cytokines in the cerebral cortex and hippocampus, as well as neuronal damage and glycerophospholipid metabolismimbalance. Subsequently, we demonstrated that sE2 induced the pro-inflammatory phenotype of microglia through ERα/NF-κB signaling pathway and downregulated the expression of cannabinoid receptor 1 in neuronal cells, which were important in the pathogenesis of depression. Conclusion These data suggest that sE2 may be nonhelpful or even detrimental to menopause-related depression, at least partly, by regulating microglial responses and glycerophospholipid metabolism.

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Involvement of the gut-brain axis in vascular depression via tryptophan metabolism: A benefit of short chain fatty acids

Cited by 13 publications

References 94 publications

SCFAs Supplementation Rescues Anxiety- and Depression-like Phenotypes Generated by Fecal Engraftment of Treatment-Resistant Depression Rats

SCFAs Supplementation Rescues Anxiety- and Depression-like Phenotypes Generated by Fecal Engraftment of Treatment-Resistant Depression Rats

Gut microbiota-derived short-chain fatty acids and depression: deep insight into biological mechanisms and potential applications

Supraphysiologic doses of 17β-Estradiol aggravate depression-like behaviors in ovariectomized mice possibly via regulating microglial responses and brain glycerophospholipid metabolism

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