Fecal Microbiota Transplantation Exerts a Protective Role in MPTP-Induced Parkinson’s Disease via the TLR4/PI3K/AKT/NF-κB Pathway Stimulated by α-Synuclein

Zhong, Zichun; Chen, Weijie; Gao, Huan; Che, Ning-Ning; Xu, Min; Yang, Lu; Zhang, Yingfang; Ye, Min

doi:10.1007/s11064-021-03411-0

Cited by 36 publications

(41 citation statements)

References 43 publications

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“…A previous study observed that ASO mice that received healthy gut microbiota showed improved motor deficits by down-regulating a-synuclein expression. Zhong et al found that FMT can alleviate physical impairment, decrease fecal SCFAs and the expression of asynuclein, and inhibit the activation of microglia in a mouse model of PD (118). Clinical observations found that probiotics can reduce the production of a-synuclein aggregates by inhibiting the reactive oxygen species level and finally alleviating the condition of patients with PD (119).…”

Section: A-synuclein Pathologymentioning

confidence: 99%

Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease

Zhu

Liu

et al. 2022

Front. Immunol.

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Parkinson’s disease (PD) is the second most common neurodegenerative disease characterized by motor dysfunction. Growing evidence has demonstrated that gut dysbiosis is involved in the occurrence, development and progression of PD. Numerous clinical trials have identified the characteristics of the changed gut microbiota profiles, and preclinical studies in PD animal models have indicated that gut dysbiosis can influence the progression and onset of PD via increasing intestinal permeability, aggravating neuroinflammation, aggregating abnormal levels of α-synuclein fibrils, increasing oxidative stress, and decreasing neurotransmitter production. The gut microbiota can be considered promising diagnostic and therapeutic targets for PD, which can be regulated by probiotics, psychobiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, diet modifications, and Chinese medicine. This review summarizes the recent studies in PD-associated gut microbiota profiles and functions, the potential roles, and mechanisms of gut microbiota in PD, and gut microbiota-targeted interventions for PD. Deciphering the underlying roles and mechanisms of the PD-associated gut microbiota will help interpret the pathogenesis of PD from new perspectives and elucidate novel therapeutic strategies for PD.

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Section: A-synuclein Pathologymentioning

confidence: 99%

Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease

Zhu

Liu

et al. 2022

Front. Immunol.

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“…Many metabolites produced by gut microbiota are closely related to health ( Lu et al., 2021 ; Zhong et al., 2021 ; Xie et al., 2021 ). Short-chain fatty acids (SCFAs), as the main products of gut microbiota, have been found to change in many diseases such as cardiovascular disease and autism ( Chambers et al., 2018 ; Tran and Mohajeri, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Differential Gut Microbiota Compositions Related With the Severity of Major Depressive Disorder

Zhong

Chen

Wang

et al. 2022

Front. Cell. Infect. Microbiol.

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ObjectiveIncreasing evidence shows a close relationship between gut microbiota and major depressive disorder (MDD), but the specific mechanisms remain unknown. This study was conducted to explore differential gut microbiota compositions related to the severity of MDD.MethodsHealthy controls (HC) (n = 131) and MDD patients (n = 130) were included. MDD patients with Hamilton Depression Rating Scale (HDRS) score <25 and ≥25 were assigned into moderate (n = 72) and severe (n = 58) MDD groups, respectively. Univariate and multivariate analyses were used to analyze the gut microbiota compositions at the genus level.ResultsThirty-six and 27 differential genera were identified in moderate and severe MDD patients, respectively. The differential genera in moderate and severe MDD patients mainly belonged to three (Firmicutes, Actinobacteriota, and Bacteroidota) and two phyla (Firmicutes and Bacteroidota), respectively. One specific covarying network from phylum Actinobacteriota was identified in moderate MDD patients. In addition, five genera (Collinsella, Eggerthella, Alistipes, Faecalibacterium, and Flavonifractor) from the shared differential genera by two MDD groups had a fair efficacy in diagnosing MDD from HC (AUC = 0.786).ConclusionsOur results were helpful for further exploring the role of gut microbiota in the pathogenesis of depression and developing objective diagnostic methods for MDD.

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“…Following the successful use of FMT in the treatment of refractory or recurrent Clostridium difficile infection, several studies have been conducted to explore FMT as a therapeutic strategy for a wide range of neurological disorders, including multiple sclerosis, epilepsy, ASD, Tourette syndrome, diabetic neuropathy, AD and PD, with promising preclinical and clinical data [ 30 , 465 , 466 , 467 , 468 ]. Concerning PD, consistent preclinical studies and a handful of human case reports have shown that FMT might be exploited to reduce motor and non-motor symptoms, as well as constipation, at least in the short term [ 40 , 465 , 469 , 470 , 471 , 472 , 473 , 474 , 475 , 476 , 477 ] ( Table 4 ). Early evidence came in 2016 from the work of Sampson et al, who first reported that the transfer of fecal matter from human PD patients to α-synuclein overexpressing mice substantially worsened their physical symptoms in comparison with mice receiving feces from healthy human donors [ 40 ].…”

Section: Parkinson’s Disease and Gut Microbiota: Therapeutic Approachesmentioning

confidence: 95%

“…These results were then confirmed in 2018, when Sun et al showed that fecal microbiota transfer from PD mice to their healthy counterpart increases motor deficits while reducing the striatal levels of the neurotransmitters dopamine, serotonin and their metabolites, thus reproducing the typical features of the disease [ 469 ]. Conversely, fecal matter transplantation from healthy mice to PD recipient mice improved physical performance, ameliorated motor symptoms and reduced dysbiosis in several independent studies [ 469 , 470 , 471 , 472 ]. Looking at the GM composition, there is evidence that FMT re-establishes eubiosis by disadvantaging the growth of Desulfovibrio , Akkermansia and Proteobacteria (orders Enterobacteriales and Turicibacteriales ), while simultaneously favoring the proliferation of beneficial bacteria such as Bacteroidetes and Actinobacteria phyla, with a particular effect on Blautia and Prevotella species [ 469 , 470 , 472 ].…”

Section: Parkinson’s Disease and Gut Microbiota: Therapeutic Approachesmentioning

confidence: 99%

“…Moreover, FMT appears to protect from gut inflammation by promoting intestinal barrier integrity and reducing the levels of LPS in the colon, serum, and SN, therefore preventing leaky gut and systemic inflammation [ 470 ]. At the brain level, FMT contrasts cognitive damage by decreasing α-synuclein expression and restoring the optimal levels of the striatal neurotransmitters dopamine and serotonin, thus supporting neuroprotection [ 469 , 471 , 473 ]. Notably, decreased neuroinflammation following FMT has been reported by numerous preclinical studies [ 469 , 470 , 471 , 472 ].…”

Section: Parkinson’s Disease and Gut Microbiota: Therapeutic Approachesmentioning

confidence: 99%

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The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment

Varesi¹,

Campagnoli²,

Fahmideh³

et al. 2022

IJMS

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The bidirectional interaction between the gut microbiota (GM) and the Central Nervous System, the so-called gut microbiota brain axis (GMBA), deeply affects brain function and has an important impact on the development of neurodegenerative diseases. In Parkinson’s disease (PD), gastrointestinal symptoms often precede the onset of motor and non-motor manifestations, and alterations in the GM composition accompany disease pathogenesis. Several studies have been conducted to unravel the role of dysbiosis and intestinal permeability in PD onset and progression, but the therapeutic and diagnostic applications of GM modifying approaches remain to be fully elucidated. After a brief introduction on the involvement of GMBA in the disease, we present evidence for GM alterations and leaky gut in PD patients. According to these data, we then review the potential of GM-based signatures to serve as disease biomarkers and we highlight the emerging role of probiotics, prebiotics, antibiotics, dietary interventions, and fecal microbiota transplantation as supportive therapeutic approaches in PD. Finally, we analyze the mutual influence between commonly prescribed PD medications and gut-microbiota, and we offer insights on the involvement also of nasal and oral microbiota in PD pathology, thus providing a comprehensive and up-to-date overview on the role of microbial features in disease diagnosis and treatment.

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Fecal Microbiota Transplantation Exerts a Protective Role in MPTP-Induced Parkinson’s Disease via the TLR4/PI3K/AKT/NF-κB Pathway Stimulated by α-Synuclein

Cited by 36 publications

References 43 publications

Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease

Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease

Differential Gut Microbiota Compositions Related With the Severity of Major Depressive Disorder

The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment

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