Key role of gut microbiota in anhedonia-like phenotype in rodents with neuropathic pain

Yang, Chun; Fang, Xi; Zhan, Gaofeng; Huang, Niannian; Li, Shan; Bi, Jiangjiang; Jiang, Ruiwei; Yang, Ling; Miao, Lei; Zhu, Bin; Luo, Ailin; Hashimoto, Kenji

doi:10.1038/s41398-019-0379-8

Cited by 138 publications

(131 citation statements)

References 41 publications

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“…One study (Yang C. et al, 2019) observed an increased pain-like phenotype in antibiotic-treated mice. Furthermore, mice that received antibiotics and FMT with feces from a neuropathic pain rat model with anhedonia-like phenotype developed more pain-symptoms compared to antibiotic-and PBS-treated mice.…”

Section: Fmt Studies In Animal Models (Table 5)mentioning

confidence: 99%

Fecal Microbiota Transplantation in Neurological Disorders

Vendrik

Ooijevaar

Jong

et al. 2020

Front. Cell. Infect. Microbiol.

255

174

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Conclusions: Preliminary literature suggests that FMT may be a promising treatment option for several neurological disorders. However, available evidence is still scanty and some contrasting results were observed. A limited number of studies in humans have been performed or are ongoing, while for some disorders only animal experiments have been conducted. Large double-blinded randomized controlled trials are needed to further elucidate the effect of FMT in neurological disorders.

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Section: Fmt Studies In Animal Models (Table 5)mentioning

confidence: 99%

Fecal Microbiota Transplantation in Neurological Disorders

Vendrik

Ooijevaar

Jong

et al. 2020

Front. Cell. Infect. Microbiol.

255

174

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“…Multiple lines of evidence suggest that gut microbiota might be involved in the pathophysiology of depression and in the antidepressant‐like effects of certain potential candidates . Recently, we investigated the possible role of gut microbiota in the antidepressant effects of ( R )‐ketamine in CSDS‐susceptible mice.…”

Section: Molecular and Cellular Mechanisms Of Ketamine’s Antidepressamentioning

confidence: 99%

Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective

Hashimoto

2019

Psychiatry Clin Neurosci

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261

193

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Major depressive disorder (MDD) is one of the most disabling psychiatric disorders. Approximately one‐third of the patients with MDD are treatment resistant to the current antidepressants. There is also a significant therapeutic time lag of weeks to months. Furthermore, depression in patients with bipolar disorder (BD) is typically poorly responsive to antidepressants. Therefore, there exists an unmet medical need for rapidly acting antidepressants with beneficial effects in treatment‐resistant patients with MDD or BD. Accumulating evidence suggests that the N‐methyl‐D‐aspartate receptor (NMDAR) antagonist ketamine produces rapid and sustained antidepressant effects in treatment‐resistant patients with MDD or BD. Ketamine is a racemic mixture comprising equal parts of (R)‐ketamine (or arketamine) and (S)‐ketamine (or esketamine). Because (S)‐ketamine has higher affinity for NMDAR than (R)‐ketamine, esketamine was developed as an antidepressant. On 5 March 2019, esketamine nasal spray was approved by the US Food and Drug Administration. However, preclinical data suggest that (R)‐ketamine exerts greater potency and longer‐lasting antidepressant effects than (S)‐ketamine in animal models of depression and that (R)‐ketamine has less detrimental side‐effects than (R,S)‐ketamine or (S)‐ketamine. In this article, the author reviews the historical overview of the antidepressant actions of enantiomers of ketamine and its major metabolites norketamine and hydroxynorketamine. Furthermore, the author discusses the other potential rapid‐acting antidepressant candidates (i.e., NMDAR antagonists and modulators, low‐voltage‐sensitive T‐type calcium channel inhibitor, potassium channel Kir4.1 inhibitor, negative modulators of γ‐aminobutyric acid, and type A [GABAA] receptors) to compare them with ketamine. Moreover, the molecular and cellular mechanisms of ketamine’s antidepressant effects are discussed.

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“…Gut microbiota is an important modulator of neuropsychiatric disorders and has been demonstrated to be closely associated with depressive‐like behaviors in rodents with stress or neuropathic pain 36,37 . However, whether gut microbiota involves in EAP‐induced depressive‐like behaviors in mice remains undetermined.…”

Section: Discussionmentioning

confidence: 99%

Abnormal gut microbiota composition is associated with experimental autoimmune prostatitis‐induced depressive‐like behaviors in mice

Liu

Zhang

et al. 2020

The Prostate

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Background: Depressive symptoms are found in approximately 78% of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients, but the pathological mechanisms remain unknown. Increasing evidence suggests that abnormal gut microbiota may play an important role in depression. Thus, we aimed to investigate whether gut microbiota contributes to CP/CPPS-associated depression by using a mouse model of experimental autoimmune prostatitis (EAP).Methods: Male nonobese diabetic mice were immunized twice by subcutaneous injection of prostate antigen and adjuvant. Behavioral tests consisted of an open field test, sucrose preference test, forced swimming tests, and tail suspension test was used to confirm the depression-like symptoms that were induced by EAP. Then, fecal samples were collected, and 16S ribosomal RNA gene sequencing was performed to detect differences in gut microbiota composition between control and EAP group. Additionally, fecal bacteria from the control and EAP mice were transplanted into antibiotics-induced pseudo-germ-free mice to investigate the effects on host behaviors and the composition of gut bacteria.Results: EAP was successfully established and exhibited depressive-like behaviors in mice. The 16S rRNA analysis of fecal samples indicated the abnormal composition of gut microbiota in the EAP mice compared to the control mice. In the fecal microbiota transplant study, antibiotics-treated pseudo-germ-free mice presented depressive states as compared to naïve mice. Fecal bacteria transplant from EAP mice, but not from control mice, into the pseudo-germ-free mice, significantly exaggerated host depression-like behaviors. Moreover, fecal bacteria transplants from control and EAP mice induced distinct alterations in α-diversity and β-diversity indices. In all, 24 bacteria at six phylogenetic levels were remarkably changed by the fecal bacteria transplantation.Conclusions: Abnormal gut microbiota composition after EAP induction may contribute to the development of depression in mice. A therapeutic strategy that targets gut microbiota may provide an alternative treatment for alleviating this condition. K E Y W O R D Sdepression, fecal bacteria transplantation, gut microbiota, prostatitis

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Key role of gut microbiota in anhedonia-like phenotype in rodents with neuropathic pain

Cited by 138 publications

References 41 publications

Fecal Microbiota Transplantation in Neurological Disorders

Fecal Microbiota Transplantation in Neurological Disorders

Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective

Abnormal gut microbiota composition is associated with experimental autoimmune prostatitis‐induced depressive‐like behaviors in mice

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