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Cited by 81Parkinson's Disease Mechanisms and TreatmentsGut microbiota and healthNeuroinflammation and Neurodegeneration Mechanisms

Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity via AMPK/SOD2 Pathway

Open access
Xie, Zhenchao, Zhang, Mahui, Luo, Yuqi, Jin, Dana, Guo, Xingfang, Yang, Wanlin, Zheng, Jialing, Zhang, Hongfei +7 more·2023·Aging and disease
DOI 10.14336/ad.2023.0309PMC PMC10676800
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Abstract

Increasing evidence has shown that gut dysbacteriosis may play a crucial role in neuroinflammation in Parkinson's disease (PD). However, the specific mechanisms that link gut microbiota to PD remain unexplored. Given the critical roles of blood-brain barrier (BBB) dysfunction and mitochondrial dysfunction in the development of PD, we aimed to evaluate the interactions among the gut microbiota, BBB, and mitochondrial resistance to oxidation and inflammation in PD. We investigated the effects of fecal microbiota transplantation (FMT) on the physiopathology of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. The aim was to explore the role of fecal microbiota from PD patients and healthy human controls in neuroinflammation, BBB components, and mitochondrial antioxidative capacity via the AMPK/SOD2 pathway. Compared to control mice, MPTP-treated mice exhibited elevated levels of Desulfovibrio, whereas mice given FMT from PD patients exhibited enriched levels of Akkermansia and mice given FMT from healthy humans showed no significant alterations in gut microbiota. Strikingly, FMT from PD patients to MPTP-treated mice significantly aggravated motor impairments, dopaminergic neurodegeneration, nigrostriatal glial activation and colonic inflammation, and inhibited the AMPK/SOD2 signaling pathway. However, FMT from healthy human controls greatly improved the aforementioned MPTP-caused effects. Surprisingly, the MPTP-treated mice displayed a significant loss in nigrostriatal pericytes, which was restored by FMT from healthy human controls. Our findings demonstrate that FMT from healthy human controls can correct gut dysbacteriosis and ameliorate neurodegeneration in the MPTP-induced PD mouse model by suppressing microgliosis and astrogliosis, ameliorating mitochondrial impairments via the AMPK/SOD2 pathway, and restoring the loss of nigrostriatal pericytes and BBB integrity. These findings raise the possibility that the alteration in the human gut microbiota may be a risk factor for PD and provide evidence for potential application of FMT in PD preclinical treatment.

AI snapshot

Written from the paper’s full text.

TL;DR

In MPTP-treated mice, fecal microbiota transplantation (FMT) from PD patients aggravated motor deficits, dopaminergic neurodegeneration, glial activation, colonic inflammation, and inhibited AMPK/SOD2, whereas FMT from healthy human controls improved these outcomes and restored nigrostriatal pericytes. The study links healthy human gut microbiota to protection via AMPK/SOD2 and gut-brain/BBB mechanisms in a sporadic PD mouse model.

Key findings

  • MPTP-treated mice had elevated *Desulfovibrio* (P < 0.001 vs. control), while PD-FMT recipients had enriched *Akkermansia* (P < 0.05 vs. control) and lower alpha diversity (Chao1 P < 0.01, Shannon P < 0.0001, Simpson P < 0.001 vs. control); healthy human FMT corrected dysbacteriosis (e.g., higher Chao1 P < 0.05 and Shannon P < 0.01 vs. MPTP + PD FMT).
  • PD FMT aggravated MPTP-induced motor deficits (shorter rotarod latency P < 0.001; longer pole descent P < 0.0001 vs. MPTP), while healthy human FMT improved them (longer rotarod latency P < 0.0001; shorter pole descent P < 0.0001 vs. MPTP). PD FMT further reduced TH+ fibers in striatum (P < 0.05) and TH+ somata in SNc (P < 0.0001) vs. MPTP; healthy FMT rescued both (P < 0.0001 vs. MPTP).
  • PD FMT increased GFAP+ and Iba-1+ glial activation in SNc/striatum; healthy FMT reduced GFAP+ cells in SNc (P < 0.0001) and striatum (P < 0.001) vs. MPTP. Colonic IL-1β was increased in MPTP mice (P < 0.01 vs. control), higher with PD FMT (P < 0.01 vs. MPTP), and suppressed by healthy FMT (P < 0.05 vs. MPTP).
  • MPTP decreased colonic p-AMPK (P < 0.001) and SOD2 (P < 0.0001) vs. control; PD FMT further lowered both (P < 0.05), while healthy FMT elevated both (P < 0.01 vs. MPTP). MPTP reduced CD13+ pericytes in striatum and SNc (P < 0.0001 vs. control); healthy FMT increased pericytes in striatum and SNc (P < 0.001 vs. MPTP), whereas PD FMT caused no significant alteration.

Methods

  • Ten-week-old male C57BL/6J mice were randomized into control, MPTP, MPTP + PD FMT, and MPTP + HC FMT groups (n = 12/group); MPTP was given i.p. at 30 mg/kg daily for 5 days, followed by oral FMT (0.2 ml/day) for 10 days from six pairs of PD patients and healthy human controls.
  • Outcomes included rotarod and pole tests, western blotting, H&E/histologic scoring, immunohistochemistry/immunofluorescence, and 16S rDNA V3-V4 sequencing (n = 7/group); analyses used one-way ANOVA with Tukey or Kruskal-Wallis with Dunn’s tests, P < 0.05.
  • Human donors with idiopathic PD met Movement Disorder Society criteria; healthy controls were matched, with exclusions including antibiotics/probiotics within 12 weeks, bowel disease, NSAID use, and unstable neurological/psychiatric illness.

Limitations

  • The paper states that more studies are required to identify the specific bacteria or metabolites contributing to neurodegeneration and to determine whether *Desulfovibrio* or *Akkermansia* directly or indirectly regulate AMPK/SOD2.
  • Evident from the text: human-to-mouse FMT and the MPTP model limit generalizability to idiopathic PD, and the study used only male mice with small donor/sample sizes.
  • Evident from the text: specific taxa and pathway relationships are largely associative; no direct causal manipulation of AMPK/SOD2 or individual microbes was performed.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.14336/ad.2023.0309

Cites

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Statistics

Nothing to recompute.

Claims the paper makes

0 of 61 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    FMT from PD patients to MPTP-treated mice significantly aggravated motor impairments.

    “FMT from PD patients to MPTP-treated mice significantly aggravated motor impairments”
    • Also stated in: § Abstract · plain
      “Specifically, FMT from PD patients significantly impairs motor function in MPTP-treated mice”
    Quote in the paperSubstantial claim
  • Findingown data

    The loss of nigrostriatal pericytes was restored by FMT from healthy human controls.

    “which was restored by FMT from healthy human controls”
    Quote in the paperSubstantial claim
  • Findingown data

    MPTP-treated mice exhibited a noticeably longer time to descend from the pole compared to control mice (P < 0.0001).

    “a noticeably longer time to descend from the pole (P < 0.0001, Fig. 1C)”
    Quote in the paperSubstantial claim
  • Findingown data

    Compared to control mice, MPTP-treated mice exhibited a significantly shorter latency to fall from the rotatory rod (P < 0.0001).

    “Compared to the control mice, the MPTP-treated mice exhibited a significantly shorter latency to fall from the rotatory rod (P < 0.0001, Fig. 1B)”
    Quote in the paperSubstantial claim
  • Findingown data

    FMT from PD patients to MPTP-treated mice significantly aggravated colonic inflammation.

    “FMT from PD patients to MPTP-treated mice significantly aggravated motor impairments, dopaminergic neurodegeneration, nigrostriatal glial activation and colonic inflammation, and inhibited the AMPK/SOD2 signaling pathway.”
    Quote in the paperSubstantial claim
  • May combine two claims. 29
  • Classified as probably not a substantial claim. 40

  • May combine two claims.

    Findingown data

    MPTP-treated mice and mice receiving FMT from PD patients showed apparent disruption of the intestinal mucosal barrier.

    “Interestingly, we noted an apparent disruption in the intestinal mucosal barrier in MPTP-treated mice and in mice from the MPTP + PD FMT group (Fig. 4C, red arrowheads indicate disruption of the intestinal mucosal barrier)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At the genus level, the MPTP+HC FMT group was the most similar to the control, and the MPTP+PD FMT group showed the greatest separation from the control group.

    “At the genus level, the MPTP + HC FMT group was the most similar to the control, and the MPTP + PD FMT group showed the greatest separation from the control group (Supplementary Fig. 1).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    LEfse analysis produced results matched those shown in Fig. 5E-J.

    “To identify a potential biomarker of gut microbiota, we conducted linear discriminant analysis effect size (LEfse) analysis, which produced results (Supplementary Fig. 1C) matched those shown in Fig. 5E-J.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Microbiota community structures in the MPTP+PD FMT group were significantly different from those in the control group, while there were no significant differences between the control group and the MPTP+HC FMT group.

    “The microbiota community structures in the MPTP + PD FMT group exhibited significant differences compared to those in the control group, while there were no significant differences between the control group and the MPTP + HC FMT group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The control group shared the most ASVs with the MPTP+HC FMT group (42.34%) and the least with the MPTP+PD FMT group (29.18%).

    “Moreover, the control group shared the most ASVs with the MPTP + HC FMT group (42.34%) and the least with the MPTP + PD FMT group (29.18%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    MPTP-treated mice had higher histologic scores of inflammatory cell infiltration in the colon than control mice, although the difference was not statistically significant.

    “While there was no statistically significant difference observed between the scores of the MPTP group and the control group, it is noteworthy that all mice in the MPTP group scored apparently higher than those of the control group (Fig. 4B).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Findingown data

    Immunohistochemistry staining of p-AMPK and SOD2 in the SNc further supported these findings (Fig. 6G-J).

    “Immunohistochemistry staining of p-AMPK and SOD2 in the SNc further supported these findings (Fig. 6G-J).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The control group had the most characteristic ASVs (1296) while the MPTP+PD FMT group had the least (640).

    “The control group had the most characteristic ASVs (1296) while the MPTP + PD FMT group had the least (640).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The MPTP + PD FMT mice showed a significant enhancement in GFAP+ cells in the SNc compared to the MPTP group (P < 0.0001).

    “the MPTP + PD FMT mice showed a significant enhancement in GFAP+ cells in both the SNc (P < 0.0001, Fig. 3B)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The control group exhibited the furthest distance from the MPTP+PD FMT group at the genus level, sharing the least ASVs with the MPTP+PD FMT group.

    “Furthermore, the control group exhibited the furthest distance from the MPTP + PD FMT group at the genus level, sharing the least ASVs with the MPTP + PD FMT group (Supplementary Fig. 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    FMT from PD patients to mice amplified the gut inflammatory impacts, while FMT from healthy human controls prevented them.

    “Interestingly, FMT from PD patients to mice amplified these impacts, while FMT from healthy human controls prevented them (Fig. 4).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Beta diversity indices of MPTP+PD FMT mice were significantly different from those of the control mice, indicating a distinct composition and structure of the gut microbiota of the MPTP+PD FMT group.

    “Additionally, the beta diversity indices of MPTP + PD FMT mice were significantly different from those of the control mice, indicating a distinct composition and structure of the gut microbiota of the MPTP + PD FMT group (Fig. 5).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    MPTP-treated mice had more inflammatory cell infiltration, significant destruction of the intestinal mucosal barrier and higher expression of IL-1β in the colon compared to control mice.

    “Furthermore, we investigated the effects of FMT on gut inflammation and found MPTP-treated mice had more inflammatory cell infiltration, significant destruction of the intestinal mucosal barrier and higher expression of IL-1βin the colon compared to the control mice.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The most significant alteration in MPTP-treated mice was the enrichment of Desulfovibrio, and the most significant alteration in PD patient fecal microbiota recipient mice was an increase in Akkermansia.

    “It is worth noting that the most significant alteration in MPTP-treated mice was the enrichment of Desulfovibrio, and the most significant alteration in PD patient fecal microbiota recipient mice was an increase in Akkermansia.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    We further verified the presence of gut dysbacteriosis in both MPTP-treated mice and PD fecal microbiota recipient mice, which were reversed by FMT from healthy human controls.

    “We further verified the presence of gut dysbacteriosis in both MPTP-treated mice and PD fecal microbiota recipient mice, which were reversed by FMT from healthy human controls (Fig. 5, Table 1, Table 2, Table 3, and Supplementary Fig. 1).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    SOD2 is a mitochondria-localized antioxidant enzyme.

    “SOD2 is a mitochondria-localized antioxidant enzyme [23]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23] Brown EE, DeWeerd AJ, Ildefonso CJ, Lewin AS, Ash JD (2019). Mitochondrial oxidative stress in the retinal pigment epithelium (RPE) led to metabolic dysfunction in both the RPE and retinal photoreceptors. Redox Biol, 24:101201. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Gut microbiota may regulate inflammation by interacting with mitochondria.

    “gut microbiota may regulate mitochondrial metabolism [21] and inflammation [22] by interacting with mitochondria”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [22] Garaude J (2019). Reprogramming of mitochondrial metabolism by innate immunity. Curr Opin Immunol, 56:17-23. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The pathology of PD might begin in the gut and gradually progress to the brain.

    “Braak et al. theorized that the pathology of PD might begin in the gut and gradually progress to the brain [14], which was partially supported by subsequent research [15]”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [14] Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003). Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging, 24:197-211. source

      Not checked in the free run.

    • cites [15] Kim S, Kwon SH, Kam TI, Panicker N, Karuppagounder SS, Lee S, et al. (2019). Transneuronal Propagation of Pathologic alpha-Synuclein from the Gut to the Brain Models Parkinson's Disease. Neuron, 103:627-641 e627. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Neurotoxicants such as MPTP, paraquat, rotenone and 6-OHDA are commonly used to induce experimental PD models by disrupting mitochondria and increasing oxidative stress.

    “Neurotoxicants, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), paraquat, rotenone and 6-hydroxydopamine (6-OHDA), are commonly used to induce experimental PD models by disrupting mitochondria and increasing oxidative stress [9]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] Dauer W, Przedborski S (2003). Parkinson's disease: mechanisms and models. Neuron, 39:889-909. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    PD patients suffer from nonmotor manifestations such as constipation.

    “PD patients also suffer from various nonmotor manifestations, such as constipation [12, 13]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [12] Chen H, Burton EA, Ross GW, Huang X, Savica R, Abbott RD, et al. (2013). Research on the premotor symptoms of Parkinson's disease: clinical and etiological implications. Environ. Health Perspect., 121:1245-1252. source

      Not checked in the free run.

    • cites [13] Liu H, Huang Z, Deng B, Chang Z, Yang X, Guo X, et al. (2023). QEEG Signatures are Associated with Nonmotor Dysfunctions in Parkinson's Disease and Atypical Parkinsonism: An Integrative Analysis. Aging Dis, 14:204-218. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Dysfunction of the BBB may contribute to the onset and progression of PD.

    “dysfunction of the BBB may contribute to the onset and progression of PD [29]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Lan G, Wang P, Chan RB, Liu Z, Yu Z, Liu X, et al. (2022). Astrocytic VEGFA: An essential mediator in blood-brain-barrier disruption in Parkinson's disease. Glia, 70:337-353. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Pericytes play an essential role in maintaining the integrity of the BBB.

    “Pericytes play an essential role in maintaining the integrity of the BBB [30]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30] Wang Q, Zheng J, Pettersson S, Reynolds R, Tan EK (2023). The link between neuroinflammation and the neurovascular unit in synucleinopathies. Sci Adv, 9:eabq1141. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Sleep deprivation causes death in mice and flies through accumulation of reactive oxygen species in the gut.

    “sleep deprivation caused mice and flies death through the accumulation of reactive oxygen species (ROS) in the gut [20]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Vaccaro A, Kaplan Dor Y, Nambara K, Pollina EA, Lin C, Greenberg ME, et al. (2020). Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut. Cell, 181:1307-1328.e1315. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    A control with only the secondary antibody was used to identify potential non-specific staining.

    “we also utilized a control with only the secondary antibody”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    FMT from PD patients to mice leads to aggravation of motor deficits via activation of microglia.

    “Sampson et al. demonstrated that fecal microbiota transplantation (FMT) from PD patients to mice led to the aggravation of motor deficits via the activation of microglia”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, et al. (2016). Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell, 167:1469-1480.e1412. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Gut dysbacteriosis is prevalent among PD patients and may be related to motor symptoms.

    “gut dysbacteriosis is prevalent among PD patients and may be related to motor symptoms [16]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16] Nishiwaki H, Ito M, Ishida T, Hamaguchi T, Maeda T, Kashihara K, et al. (2020). Meta-Analysis of Gut Dysbiosis in Parkinson's Disease. Mov Disord, 35:1626-1635. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Mice were randomly divided into four groups.

    “The mice were randomly divided into four groups”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    FMT from normal control mice into neurotoxin-induced PD mice protects dopaminergic neurons by suppressing the TLR4 inflammatory pathway.

    “FMT from normal control mice into neurotoxin-induced PD mice could protect dopaminergic neurons by suppressing the TLR4 inflammatory pathway [18, 19]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [18] Sun MF, Zhu YL, Zhou ZL, Jia XB, Xu YD, Yang Q, et al. (2018). Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson's disease mice: Gut microbiota, glial reaction and TLR4/TNF-α signaling pathway. Brain Behav Immun, 70:48-60. source

      Not checked in the free run.

    • cites [19] Zhao Z, Ning J, Bao XQ, Shang M, Ma J, Li G, et al. (2021). Fecal microbiota transplantation protects rotenone-induced Parkinson's disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis. Microbiome, 9:226. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Mitochondrial malfunction is a key determinant of dopaminergic neurodegeneration and an overlapping risk factor for sporadic and familial PD.

    “mitochondrial malfunction is increasingly considered a key determinant of dopaminergic neurodegeneration, serving as an overlapping risk factor for both sporadic and familial cases [11]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Ryan BJ, Hoek S, Fon EA, Wade-Martins R (2015). Mitochondrial dysfunction and mitophagy in Parkinson's: from familial to sporadic disease. Trends Biochem Sci, 40:200-210. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The isotype control of the primary antibody was used as a negative control to determine the specificity of the primary antibody.

    “to determine the specificity of the primary antibody, we employed the isotype control of the primary antibody as a negative control”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Fecal microbiota from PD patients may promote damage, while fecal microbiota from healthy controls might attenuate disruption and inflammation.

    “The fecal microbiota from PD patients may promote damage, but the fecal microbiota from healthy controls might attenuate disruption and inflammation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Fecal microbiota from PD patients may aggravate motor disorders in MPTP-treated mice by increasing the loss of TH+ neurons, whereas fecal microbiota from healthy human controls may alleviate these disorders by reducing the loss of TH+ neurons in mice.

    “Taken together, the fecal microbiota from PD patients may aggravate motor disorders in MPTP-treated mice by increasing the loss of TH+ neurons, whereas the fecal microbiota from healthy human controls may alleviate these disorders by reducing the loss of TH+ neurons in mice.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    MPTP can disrupt the intestinal mucosal barrier and cause gut inflammation.

    “These results suggested that MPTP can disrupt the intestinal mucosal barrier and cause gut inflammation.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Previous studies have demonstrated that FMT from healthy control mice relieved motor impairments in MPTP/rotenone-induced PD mice.

    “Consistently, previous studies have demonstrated that FMT from healthy control mice relieved motor impairments in MPTP/rotenone-induced PD mice [18, 19].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [18] Sun MF, Zhu YL, Zhou ZL, Jia XB, Xu YD, Yang Q, et al. (2018). Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson's disease mice: Gut microbiota, glial reaction and TLR4/TNF-α signaling pathway. Brain Behav Immun, 70:48-60. source

      Not checked in the free run.

    • cites [19] Zhao Z, Ning J, Bao XQ, Shang M, Ma J, Li G, et al. (2021). Fecal microbiota transplantation protects rotenone-induced Parkinson's disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis. Microbiome, 9:226. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    MPTP may damage pericytes, but gut microbiota from healthy controls may play a potential protective role in pericytes in MPTP-injected mice.

    “These results indicated that MPTP may damage pericytes, but gut microbiota from healthy controls may play a potential protective role in pericytes in MPTP-injected mice.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Nigrostriatal vascular leakage has been reported in MPTP-treated mice.

    “nigrostriatal vascular leakage has been reported in MPTP-treated mice [73]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [73] Chen X, Lan X, Roche I, Liu R, Geiger JD (2008). Caffeine protects against MPTP-induced blood-brain barrier dysfunction in mouse striatum. [J]. Neurochem., 107:1147-1157. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A notable increase in pericytes was observed in the lesioned striatum of 6-hydroxydopamine (6-OHDA)-induced PD mice.

    “a notable increase in pericytes was observed in the lesioned striatum of 6-hydroxydopamine (6-OHDA)-induced PD mice [74]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [74] Padel T, Özen I, Boix J, Barbariga M, Gaceb A, Roth M, et al. (2016). Platelet-derived growth factor-BB has neurorestorative effects and modulates the pericyte response in a partial 6-hydroxydopamine lesion mouse model of Parkinson's disease. Neurobiol Dis, 94:95-105. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Desulfovibrio, one of the main H2S-producing gut bacteria, is known to be associated with PD due to its elevated abundance.

    “Desulfovibrio, one of the main H2S-producing gut bacteria [59], is known to be associated with PD due to its elevated abundance [60].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [59] Xu C, Zhu H, Qiu P (2019). Aging progression of human gut microbiota. BMC Microbiol, 19:236. source

      Not checked in the free run.

    • cites [60] Murros KE, Huynh VA, Takala TM, Saris PEJ (2021). Desulfovibrio Bacteria Are Associated With Parkinson's Disease. Front Cell Infect Microbiol, 11:652617. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A decrease in short-chain fatty acids (SCFAs) in feces has been implicated in the development of Parkinson's disease.

    “a decrease in short-chain fatty acids (SCFAs) in feces has been implicated in the development of PD [66]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [66] Aho VTE, Houser MC, Pereira PAB, Chang J, Rudi K, Paulin L, et al. (2021). Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson's disease. Mol Neurodegener, 16:6. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    L. plantarum DP189 slows neurodegeneration via inhibition of oxidative stress, reduction of the proinflammatory response, and modification of the gut microbiota in mice.

    “L. plantarum DP189 was found to slow neurodegeneration via inhibition of oxidative stress, reduction of the proinflammatory response, and modification of the gut microbiota in mice [71]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [71] Wang L, Zhao Z, Zhao L, Zhao Y, Yang G, Wang C, et al. (2022). Lactobacillus plantarum DP189 Reduces α-SYN Aggravation in MPTP-Induced Parkinson's Disease Mice via Regulating Oxidative Damage, Inflammation, and Gut Microbiota Disorder. J Agric Food Chem, 70:1163-1173. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A reduction in Muribaculaceae was reported in PD animal models, which is in agreement with the significant reduction of Bacteroidota, the phylum containing the Muribaculaceae genus, in both PD patients and PD animal models.

    “In addition, a reduction in Muribaculaceae was reported in PD animal models [61], which is in agreement with the significant reduction of Bacteroidota, the phylum containing the Muribaculaceae genus, in both PD patients [62] and PD animal models [63].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [61] Liu Y, Liu X, Ye Q, Wang Y, Zhang J, Lin S, et al. (2022). Fucosylated Chondroitin Sulfate against Parkinson's Disease through Inhibiting Inflammation Induced by Gut Dysbiosis. J Agric Food Chem, 70:13676-13691. source

      Not checked in the free run.

    • cites [62] Unger MM, Spiegel J, Dillmann K-U, Grundmann D, Philippeit H, Bürmann J, et al. (2016). Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls. Parkinsonism Relat Disord, 32:66-72. source

      Not checked in the free run.

    • cites [63] Hou YF, Shan C, Zhuang SY, Zhuang QQ, Ghosh A, Zhu KC, et al. (2021). Gut microbiota-derived propionate mediates the neuroprotective effect of osteocalcin in a mouse model of Parkinson's disease. Microbiome, 9:34. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Trimethylamine-N-oxide may enhance inflammation and oxidative stress.

    “trimethylamine-N-oxide may enhance inflammation and oxidative stress [68]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Voigt RM, Wang Z, Brown JM, Engen PA, Naqib A, Goetz CG, et al. (2022). Gut microbial metabolites in Parkinson's disease: Association with lifestyle, disease characteristics, and treatment status. Neurobiol Dis, 170:105780. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    N6-carboxymethyllysine may promote mitochondrial impairment and oxidative stress in microglia.

    “N6-carboxymethyllysine may promote mitochondrial impairment and oxidative stress in microglia [69]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [69] Mossad O, Batut B, Yilmaz B, Dokalis N, Mezö C, Nent E, et al. (2022). Gut microbiota drives age-related oxidative stress and mitochondrial damage in microglia via the metabolite N(6)-carboxymethyllysine. Nat. Neurosci., 25:295-305. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    FMT from PD patients can significantly worsen motor dysfunction in α-synuclein-overexpressing (ASO) mice compared to genotype-matched recipient mice receiving FMT from healthy human controls.

    “FMT from PD patients can significantly worsen motor dysfunction in α-synuclein-overexpressing (ASO) mice compared to genotype-matched recipient mice receiving FMT from healthy human controls [17]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, et al. (2016). Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell, 167:1469-1480.e1412. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    6-OHDA is commonly administered to the striatum via stereotaxic injection due to the blood-brain barrier's impermeability to the compound.

    “6-OHDA is commonly administered to the striatum via stereotaxic injection due to BBB's impermeability to the compound [75]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [75] Thomsen M, Stoica A, Christensen KV, Fryland T, Mikkelsen JD, Hansen JB (2022). Synergistic effect of serotonin 1A and serotonin 1B/D receptor agonists in the treatment of L-DOPA-induced dyskinesia in 6-hydroxydopamine-lesioned rats. Experimental Neurology, 358:114209. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Acute administration of hydrogen sulfide (H2S) into airway can induce cytochrome oxidase inhibition in the animal brain, impairing mitochondrial function.

    “Acute administration of hydrogen sulfide (H2S) into airway can induce cytochrome oxidase inhibition in the animal brain, impairing mitochondrial function [57].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] Dorman DC, Moulin FJ, McManus BE, Mahle KC, James RA, Struve MF (2002). Cytochrome oxidase inhibition induced by acute hydrogen sulfide inhalation: correlation with tissue sulfide concentrations in the rat brain, liver, lung, and nasal epithelium. Toxicol Sci, 65:18-25. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    FMT from control mice enhanced pericyte coverage in a spinal cord injury mouse model.

    “FMT from control mice enhanced pericyte coverage in a spinal cord injury mouse model [77]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [77] Jing Y, Bai F, Wang L, Yang D, Yan Y, Wang Q, et al. (2022). Fecal Microbiota Transplantation Exerts Neuroprotective Effects in a Mouse Spinal Cord Injury Model by Modulating the Microenvironment at the Lesion Site. Microbiol Spectr, 10:e0017722. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Lipopolysaccharide (LPS) plays a key role in the communication between the gut and the brain, as it has a remarkable proinflammatory effect.

    “Lipopolysaccharide (LPS) appears to play a key role in the communication between the gut and the brain, as it has a remarkable proinflammatory effect [70]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [70] César H, Nascimento Sertorio M, Santamarina A, Alves de Souza E, Valles Mennitti L, Jamar G, et al. (2022). The influence of parental high-fat high-sugar diet on the gut-brain axis in male offspring. Food Res Int, 160:111706. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Gut dysbacteriosis, especially abnormally enriched Akkermansia, may enhance the disruption of gut barriers and promote inflammation in both the gut and brain of mice in the MPTP+PD FMT group.

    “Collectively, gut dysbacteriosis, especially abnormally enriched Akkermansia, may enhance the disruption of gut barriers and promote inflammation in both the gut and brain of mice in the MPTP + PD FMT group.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Several studies have reported a higher abundance of Akkermansia in PD patients compared to healthy controls.

    “Several studies have reported a higher abundance of Akkermansia in PD patients compared to healthy controls [16, 53]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [16] Nishiwaki H, Ito M, Ishida T, Hamaguchi T, Maeda T, Kashihara K, et al. (2020). Meta-Analysis of Gut Dysbiosis in Parkinson's Disease. Mov Disord, 35:1626-1635. source

      Not checked in the free run.

    • cites [53] Yan Y, Ren S, Duan Y, Lu C, Niu Y, Wang Z, et al. (2021). Gut microbiota and metabolites of α-synuclein transgenic monkey models with early stage of Parkinson's disease. NPJ Biofilms Microbiomes, 7:69. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    An increase in Akkermansia has been linked to reduced mucus and decreased resistance to a specific pathogen in mice.

    “Nevertheless, an increase in Akkermansia has also been linked to reduced mucus and decreased resistance to a specific pathogen in mice [55].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] Desai MS, Seekatz AM, Koropatkin NM, Kamada N, Hickey CA, Wolter M, et al. (2016). A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility. Cell, 167:1339-1353.e1321. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Akkermansia is generally thought to be a probiotic bacterium owing to its protective effects on gut barrier function and anti-inflammatory properties.

    “although Akkermansia is generally thought to be a probiotic bacterium owing to its protective effects on gut barrier function and anti-inflammatory properties [54].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Heintz-Buschart A, Pandey U, Wicke T, Sixel-Döring F, Janzen A, Sittig-Wiegand E, et al. (2018). The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder. Mov Disord, 33:88-98. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    H2S exhibits a dual effect, being cytoprotective at low concentrations but toxic at high concentrations.

    “However, H2S exhibits a dual effect, being cytoprotective at low concentrations but toxic at high concentrations [58].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [58] Buret AG, Allain T, Motta JP, Wallace JL (2022). Effects of Hydrogen Sulfide on the Microbiome: From Toxicity to Therapy. Antioxid Redox Signal, 36:211-219. source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Pericyte deficiency is sufficient to significantly increase the permeability of the blood-brain barrier and cause damage to neurons.

    “pericyte deficiency is sufficient to significantly increase the permeability of the BBB and cause damage to neurons [72]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [72] Armulik A, Genové G, Mäe M, Nisancioglu MH, Wallgard E, Niaudet C, et al. (2010). Pericytes regulate the blood-brain barrier. Nature, 468:557-561. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Some bacteria or their metabolites in the feces of PD patients may stimulate glial activation, or FMT from PD patients may enhance proinflammatory responses by amplifying gut dysbacteriosis.

    “suggesting that some bacteria or their metabolites in the feces of PD patients may stimulate glial activation, or that FMT from PD patients may enhance proinflammatory responses by amplifying gut dysbacteriosis.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Administration of SCFAs suppresses the secretion of proinflammatory cytokines by activating microglia-like cells.

    “administration of SCFAs has been shown to suppresses the secretion of proinflammatory cytokines by activating microglia-like cells [67]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] Wenzel TJ, Gates EJ, Ranger AL, Klegeris A (2020). Short-chain fatty acids (SCFAs) alone or in combination regulate select immune functions of microglia-like cells. Mol. Cell. Neurosci, 105:103493. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Butyrate, a type of SCFA, can increase mitochondrial inner membrane proton leakage and decrease ROS.

    “butyrate, a type of SCFA, can increase mitochondrial inner membrane proton leakage and decrease ROS [78]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [78] Mafra D, Borges NA, Lindholm B, Stenvinkel P (2019). Mitochondrial dysfunction and gut microbiota imbalance: An intriguing relationship in chronic kidney disease. Mitochondrion, 47:206-209. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    FMT from healthy control mice exerted a neuroprotective effect in neurotoxin-induced PD mice.

    “FMT from healthy control mice exerted a neuroprotective effect in neurotoxin-induced PD mice [18, 19]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [18] Sun MF, Zhu YL, Zhou ZL, Jia XB, Xu YD, Yang Q, et al. (2018). Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson's disease mice: Gut microbiota, glial reaction and TLR4/TNF-α signaling pathway. Brain Behav Immun, 70:48-60. source

      Not checked in the free run.

    • cites [19] Zhao Z, Ning J, Bao XQ, Shang M, Ma J, Li G, et al. (2021). Fecal microbiota transplantation protects rotenone-induced Parkinson's disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis. Microbiome, 9:226. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Probiotic administration helped repair 6-OHDA-induced motor deficits by enhancing mitochondrial function in PD rats.

    “probiotic administration helped repair 6-OHDA-induced motor deficits by enhancing mitochondrial function in PD rats [79]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [79] Tsao SP, Nurrahma BA, Kumar R, Wu CH, Yeh TH, Chiu CC, et al. (2021). Probiotic Enhancement of Antioxidant Capacity and Alterations of Gut Microbiota Composition in 6-Hydroxydopamin-Induced Parkinson's Disease Rats. Antioxidants(Basel), 10. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    FMT from PD patients likely inhibited the AMPK/SOD2 pathway and aggravated gut dysbacteriosis.

    “likely by inhibiting the AMPK/SOD2 pathway and aggravating gut dysbacteriosis”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Dopaminergic neurons have high energy requirements, and their mitochondria produce a large amount of ROS, which are constantly eliminated through antioxidant defenses such as SOD2.

    “Given the high energy requirements of dopaminergic neurons, their mitochondria produce a large amount of ROS, which are constantly eliminated through antioxidant defenses, such as SOD2 [80]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [80] Halliwell B (2006). Oxidative stress and neurodegeneration: where are we now? [J]. Neurochem., 97:1634-1658. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    FMT from healthy human controls alleviated MPTP neurotoxicity by upregulating the AMPK/SOD2 pathway and adjusting gut dysbacteriosis.

    “while FMT from healthy human controls alleviated this neurotoxicity by upregulating the AMPK/SOD2 pathway and adjusting gut dysbacteriosis”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Gut microbiota from healthy human controls may regulate mitochondrial oxidation resistance to neuroinflammation and rescue nigrostriatal pericyte loss and blood-brain barrier disruption mediated by MPTP in PD mice.

    “Our results suggest that the gut microbiota from healthy human controls may regulate mitochondrial oxidation resistance to neuroinflammation and rescue nigrostriatal pericyte loss and BBB disruption mediated by MPTP in PD mice.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    AMPK activation decreases mitochondrial ROS by upregulating SOD2 in a diabetes animal model.

    “AMPK activation has been reported to decrease mitochondrial ROS by upregulating SOD2 in a diabetes animal model [82]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [82] Kukidome D, Nishikawa T, Sonoda K, Imoto K, Fujisawa K, Yano M, et al. (2006). Activation of AMP-activated protein kinase reduces hyperglycemia-induced mitochondrial reactive oxygen species production and promotes mitochondrial biogenesis in human umbilical vein endothelial cells. Diabetes, 55:120-127. source

      Not checked in the free run.

64 of 64

  • The paper relies on this without support.

    Loss of pericytes increases BBB permeability, allowing harmful intestinal substances to enter the brain and damage neurons.

    “loss of pericytes may increase BBB permeability, allowing harmful intestinal substances to enter the brain and damage neurons”

  • The paper relies on this without support.

    Human fecal microbiota transplanted into MPTP-treated mice establishes and functionally represents the donor human gut microbiota.

    “To demonstrate the effect of FMT from PD patients and healthy human controls on the colon in MPTP-treated mice, we tested inflammation in the gut via H&E staining, immunofluorescence and western blotting.”

  • The paper relies on this without support.

    The MPTP-treated mouse model is a valid model of Parkinson's disease for assessing gut microbiota effects on neurotoxicity.

    “Our study successfully established the PD mouse model as demonstrated by significant loss of TH+ fibers in the striatum and TH+ somas in the SNc following MPTP administration.”

  • The paper relies on this without support.

    The observed differences in gut microbiota composition between groups are due to the transplanted human fecal microbiota rather than other factors.

    “To investigate the alterations in gut microbiota in the four groups of mice, we performed 16S rDNA sequencing on mice feces.”

  • The paper relies on this without support.

    The stereotaxic injection method causes unavoidable injury resulting from the needle passing through the brain tissue, such as hemorrhage.

    “This injection method causes unavoidable injury resulting from the needle passing through the brain tissue, such as hemorrhage.”

  • The paper relies on this without support.

    There is little evidence suggesting that stereotactic 6-OHDA injection can create significant alterations in the gut microbiota in PD animal models.

    “there is little evidence suggesting that stereotactic 6-OHDA injection can create significant alterations in the gut microbiota in PD animal models”

  • The paper relies on this without support.

    MPTP-treated mice are the most commonly used PD animal model that can mimic sporadic PD to some extent.

    “MPTP-treated mice, the most commonly used PD animal model that can mimic sporadic PD to some extent”

  • The paper relies on this without support.

    Alterations in nigrostriatal pericytes in MPTP-induced PD mouse models have not yet been reported.

    “To the best of our knowledge, alterations in nigrostriatal pericytes in MPTP-induced PD mouse models have not yet been reported.”

  • The paper relies on this without support.

    The relationship between mitochondria and fecal microbiota in neurotoxin-induced PD mice remains largely unknown.

    “The relationship between mitochondria and fecal microbiota in neurotoxin-induced PD mice remains largely unknown.”
9 of 9

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Amelioration of gut dysbiosis in MPTP-induced mice via FMT, dietary intervention, and probiotic administration alleviates neuroinflammation and dopaminergic neuron loss.

    “The amelioration of gut dysbiosis in MPTP-induced mice via FMT, dietary intervention, and probiotic administration has been shown to alleviate neuroinflammation and dopaminergic neuron loss.”

    From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [261]

  • The alleviation of neuroinflammation and dopaminergic neuron loss by gut dysbiosis amelioration is attributed to reduction of glial activation and restoration of metabolite and neurotransmitter abnormalities.

    “These effects are attributed to the reduction of glial activation, as well as the restoration of metabolite and neurotransmitter abnormalities.217,259–261”

    From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [261]

  • FMT from healthy human controls mitigates MPTP-induced dysbiosis and neurotoxicity in MPTP-induced mice, whereas FMT from PD patients exacerbates these pathologies.

    “In addition, it was found that FMT from healthy human controls mitigated MPTP-induced dysbiosis and neurotoxicity in MPTP-induced mice, whereas FMT from PD patients exacerbated these pathologies.261”

    From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [261]

  • Transplantation of healthy human faecal microbiota protects integrity of the BBB and reduces entry of gut-derived harmful substances into the brain, thereby alleviating neuroinflammation and neurodegeneration in PD mice.

    “transplantation of healthy human faecal microbiota protects integrity of the BBB and reduces the entry of gut-derived harmful substances into the brain, thereby alleviating neuroinflammation and neurodegeneration in PD mice.461”

    From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [461]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Table 3 gives conflicting analysis and summary formats for Desulfovibrio

    Minor

    The Desulfovibrio row presents mean ± SEM values, but the table note places Desulfovibrio among taxa analyzed by Kruskal-Wallis and presented as median (IQR).

  • The same SNc comparison is described as both neuronal loss and rescue

    Minor

    The text says healthy-control FMT rescued TH+ somata in the SNc, but the parenthetical identifies the PD-FMT-versus-MPTP comparison. That same comparison is earlier said to show further loss, not rescue.

  • Table 2 gives conflicting analysis and summary formats for Desulfobacterota

    Minor

    The Desulfobacterota row presents values in median (IQR) format, but the table note says Desulfobacterota was analyzed by ANOVA and presented as mean ± SEM.

  • Figure 1 assigns three stars a different P-value threshold

    Minor

    The Figure 1 caption defines *** as P < 0.01, whereas the statistical-analysis section defines *** as P < 0.001 and ** as P < 0.01.

4 of 4

Cites

Flagged first, then by citations

2 of the 84 references couldn’t be matched to a known paper.

Cited by

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Related

Authors
Xie, Z., Zhang, M., Luo, Y., Jin, D., Guo, X., Yang, W., Zheng, J., Zhang, H., Zhang, L., Deng, C., Zheng, W., Tan, E.-K., Jin, K., Zhu, S., & Wang, Q.
Affiliations
  • Zhujiang Hospital (CN)
  • University of California, Davis (US)
  • Southern Medical University (CN)
  • University of Wollongong (AU)
  • University of Macau (MO)
  • Singapore General Hospital (SG)
  • University of North Texas Health Science Center (US)
Corresponding author
  • Zhu, Shuzhen
  • Wang, Qing
ORCID
Venue
Aging and disease
Publisher
Aging and Disease
Published
2023
Volume
14
Issue
6
Pages
2193
ISSN
2152-5250 (ISSN-L)
DOI
10.14336/ad.2023.0309
PMC
PMC10676800
OpenAlex
W4377011041
Semantic Scholar
099531e0ac8b462a1987f1aa46a0a8d0fdeaa676
Cited by
80
References
84
Citations by year
2026: 27 · 2025: 28 · 2024: 21 · 2023: 4
FWCI
13.54
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Aging and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Online (University of Wollongong) (submittedVersion)
Funders
  • National Natural Science Foundation of China (81873777, 82071414, 82171253)
  • Science and Technology Planning Project of Guangdong Province
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Parkinson's disease, fecal microbiota transplantation, MPTP-induced neurotoxicity, blood-brain barrier, mitochondrial dysfunction, neuroinflammation, microglial activation, astrocyte activation, dopaminergic neuron loss, Akkermansia, Desulfovibrio, colonic inflammation, motor impairment

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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