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Cited by 88Parkinson's Disease Mechanisms and TreatmentsGut microbiota and healthGastrointestinal motility and disorders

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

Open access
Varesi, Angelica, Campagnoli, Lucrezia Irene Maria, Fahmideh, Foroogh, Pierella, Elisa, Romeo, Marcello, Ricevuti, Giovanni, Nicoletta, Marchesi, Chirumbolo, Salvatore +1 more·2022·International Journal of Molecular Sciences
DOI 10.3390/ijms232012289PMC PMC9603886
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Abstract

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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Written from the paper’s full text.

TL;DR

This narrative review synthesizes evidence that gut dysbiosis and increased intestinal permeability are linked to Parkinson’s disease (PD) and may contribute to diagnosis, progression, and treatment. It reviews GM-based biomarkers and interventions including probiotics, prebiotics, antibiotics, diet, and fecal microbiota transplantation (FMT), while noting conflicting findings and the need for larger trials.

Key findings

  • PD patients show gut microbiota dysbiosis, including overgrowth of *Bifidobacterium*, *Lactobacillus*, *Akkermansia*, *Porphyromonas*, and *Corynebacterium*, with decreased SCFA producers *Prevotellaceae*, *Lachnospiraceae*, and *Faecalibacterium*; lower butyrate is linked to postural instability, gait disorders, MDS-UPDRS part III motor scores, and depression. Leaky gut markers zonulin, α1-antitrypsin, calprotectin, and lactoferrin are elevated in PD feces, and LPS/endotoxemia may drive inflammation and α-synuclein aggregation.
  • Proposed GM-based biomarkers include metagenomic sequencing plus random forest machine learning; 25 genetic microbial markers distinguished PD, Alzheimer’s disease, and multiple system atrophy. Reduced *Prevotellaceae* plus increased *Akkermansia* was proposed as a PD diagnostic signature; plasma acetic and propionic acid discriminated multiple system atrophy from PD with 80% sensitivity and 91% specificity; 11 oral taxonomic features reached 84.5% accuracy. A shortage of *Roseburia* in de novo PD predicted faster motor, non-motor, and intellectual decline within 3 years; low *Barnesiella* was associated with worse clinical evolution.
  • Therapeutic approaches reviewed include probiotics, prebiotics, antibiotics, diet, and FMT. FMT reduced constipation and motor/non-motor symptoms in human case series of 6, 11, and 15 PD patients; adverse events in 6 cases included flatulence (1), diarrhea (2), hospitalization under observation (1), and GI pain (2). A Finnish study of 13,976 PD and 40,697 healthy individuals linked macrolides and lincosamides to increased PD risk, while another prospective study of 59,637 women found no correlation between antibiotic intake and PD incidence.
  • Drug–microbiota interactions are bidirectional: L-dopa is metabolized by *E. faecalis*, *Eggerthella lenta*, and *C. sporogenes*, and *H. pylori* binding reduces L-dopa absorption; L-dopa and COMT inhibitors also reshape GM composition. Oral and nasal microbiota are altered in PD, with *Moraxella catarrhalis* abundance positively correlated with motor symptoms, but nasal findings remain inconsistent.

Methods

  • Narrative review; no systematic review or meta-analysis methods are stated. It synthesizes preclinical and clinical literature on the gut microbiota–brain axis, dysbiosis, gut permeability, biomarkers, drug interactions, and GM-modifying interventions.
  • Data are published studies, including animal models, in vitro models, human cohorts, case reports, and clinical trials; no primary data collection is reported. The main analysis is qualitative synthesis, with tables summarizing probiotics, prebiotics, diet, and FMT evidence.

Limitations

  • Stated: GM studies show discrepancy and variability that limit reproducibility; common laboratory protocols, bioinformatics pipelines, and shared analysis methods are needed. Geography, diet, lifestyle, and host genetics confound results; comparisons between treated and treatment-naive patients are lacking; the optimal probiotic-prebiotic cocktail and best dietary intervention are unknown; FMT protocols, delivery methods, donor/patient criteria, long-term benefits, and risks remain unresolved; antibiotics risk dysbiosis and resistance, with scarce long-term safety data; many findings are conflicting.
  • Evident: as a narrative review, no systematic search strategy, inclusion criteria, or risk-of-bias assessment is reported; the evidence base includes many small, preclinical, or single-arm studies, and human FMT data are limited to small case series.

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Registry

Crossref · 10.3390/ijms232012289

Cites

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Statistics

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Claims the paper makes

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  • Premisecitation

    SCFAs-producing bacteria are reduced in Parkinson's disease.

    “some evidence reported that SCFAs-producing bacteria are reduced in PD [13]”
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    • cites [13] Hirayama, 2021, Parkinson’s Disease and Gut Microbiota, Ann. Nutr. Metab. source

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  • Premisecitation

    Desulfovibrio bacteria are strictly associated with Parkinson's disease.

    “Notably, Desulfovibrio bacteria have been strictly associated with PD [21]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Murros, 2021, Desulfovibrio Bacteria Are Associated With Parkinson’s Disease, Front. Cell Infect Microbiol. source

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  • Premisecitation

    Feces from Parkinson's disease patients are enriched in opportunistic pathogens and pro-inflammatory taxa at the expense of anti-inflammatory microbes and SCFAs-producing bacteria, especially butyrate.

    “feces from PD patients are enriched in opportunistic pathogens and pro-inflammatory taxa at the expense of anti-inflammatory microbes and SCFAs-producing bacteria, especially butyrate [47,48,49,50,51]”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [47] Zhang, 2020, Altered Gut Microbiota in Parkinson’s Disease Patients/Healthy Spouses and Its Association with Clinical Features, Park. Relat. Disord. source

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    • cites [48] Wallen, 2020, Characterizing Dysbiosis of Gut Microbiome in PD: Evidence for Overabundance of Opportunistic Pathogens, NPJ Park. Dis. source

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  • Premisecitation

    Gut microbiota composition changes according to ethnicity and geographic location.

    “There is evidence that GM composition changes according to ethnicity and geographic location [91,92]”
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    • cites [91] Porras, 2021, Geographic Differences in Gut Microbiota Composition Impact Susceptibility to Enteric Infection, Cell Rep. source

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    • cites [92] Gupta, 2017, Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity, Front. Microbiol. source

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    Reduced presence of Lachnospiraceae, especially Ruminococcus, is associated with cognitive impairment as measured by the Mini Mental State Examination and postural instability in Parkinson's disease patients.

    “Their reduced presence, especially that of Ruminococcus, has been associated with cognitive impairment as measured by the Mini Mental State Examination (MMSE) test and postural instability in PD patients [59,68,69,70]”
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    • cites [59] Meixner, 2020, Changes in Gastrointestinal Microbiome Composition in PD: A Pivotal Role of Covariates, Front. Neurol. source

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    • cites [68] Lin, 2018, Gut Microbiota in Patients with Parkinson’s Disease in Southern China, Park. Relat. Disord. source

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    • cites [70] Li, 2022, Oral, Nasal, and Gut Microbiota in Parkinson’s Disease, Neuroscience source

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    Premisecitation

    Parkinson's disease patients are characterized by an overgrowth of the genera Bifidobacterium, Lactobacillus, Akkermansia and of the opportunistic pathogens Porphyromonas and Corynebacterium, together with a decreased abundance of the SCFAs producers Prevotellaceae, Lachnospiraceae and Faecalibacterium.

    “meta-analysis and systematic reviews report that PD patients are characterized by an overgrowth of the genera Bifidobacterium, Lactobacillus, Akkermansia and of the opportunistic pathogens Porphyromonas and Corynebacterium, together with a decreased abundance of the SCFAs producers Prevotellaceae, Lachnospiraceae and Faecalibacterium [52,53,54,55,56]”
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    Premisecitation

    The gut microbiota-brain axis (GMBA) is a bidirectional functional system linking the enteric nervous system in the gastrointestinal tract with the brain.

    “GMBA is usually described as a bidirectional functional system linking the enteric nervous system (ENS) in the gastrointestinal tract with the brain [5]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] Carabotti, 2015, The Gut-Brain Axis: Interactions between Enteric Microbiota, Central and Enteric Nervous Systems, Ann. Gastroenterol.

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    Premisecitation

    A gut bacterial amyloid promotes the aggregation of α-synuclein, causing motor impairments in experimental mice.

    “recent evidence has shown that a gut bacterial amyloid promotes the aggregation of α-synuclein, causing motor impairments in experimental mice [15]”
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    • cites [15] Sampson, 2020, A Gut Bacterial Amyloid Promotes α-Synuclein Aggregation and Motor Impairment in Mice, Elife source

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    Premisecitation

    In Parkinson's disease, dysbiosis followed by gastrointestinal symptoms and gut discomfort far precedes the onset of motor dysfunctions and is linked to neuroinflammation and alterations in dopamine, serotonin, and kynurenine metabolism through the gut-brain axis.

    “Concerning PD, dysbiosis followed by GI symptoms and gut discomfort far precedes the onset of motor dysfunctions and it is linked to neuroinflammation, as well as to alterations in dopamine, serotonin, and kynurenine metabolism through the gut-brain axis [40,41,42,43,44,45,46]”
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    • cites [40] Sampson, 2016, Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease, Cell source

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    • Rests on an assumption: Associations between gut microbiota composition and Parkinson’s disease symptoms reflect causal relationships rather than reverse causation or confounding.

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    α-synuclein is produced by enteric neurons in the enteric nervous system, probably with functions related to uptake and neurotransmission.

    “α-synuclein is produced by the enteric neurons in the ENS, probably with functions related to uptake and neurotransmission [14]”
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    • cites [14] Grathwohl, 2013, Mind the Gut: Secretion of α-Synuclein by Enteric Neurons, J. Neurochem. source

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    Premisecitation

    TMAO is implicated in oxidative stress enhancement, blood-brain barrier disruption, mitochondria dysfunction, brain aging and neurodegeneration.

    “TMAO is an amine oxide product of the bacterial metabolism that has been implicated in oxidative stress enhancement, BBB disruption, mitochondria dysfunction, brain aging and neurodegeneration [105,106,107]”
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    • cites [105] Spillane, 2022, Alzheimer’s Disease and Gut Microbiota: Does Trimethylamine N-Oxide (TMAO) Play a Role?, Nutr. Rev. source

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    • cites [107] Li, 2018, Trimethylamine-N-Oxide Promotes Brain Aging and Cognitive Impairment in Mice, Aging Cell source

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    Premisecitation

    Higher concentrations of the leaky gut markers zonulin and α1-antitrypsin, as well as enhanced abundance of the colonic inflammatory markers calprotectin and lactoferrin, were noticed in feces from Parkinson's disease patients compared to controls.

    “higher concentrations of the leaky gut markers zonulin and α1-antitrypsin, as well as enhanced abundance of the colonic inflammatory markers calprotectin and lactoferrin, were noticed in feces from PD patients compared to controls [132,133,134]”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [132] Schwiertz, 2018, Fecal Markers of Intestinal Inflammation and Intestinal Permeability Are Elevated in Parkinson’s Disease, Park. Relat. Disord. source

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    • cites [133] Dumitrescu, 2021, Serum and Fecal Markers of Intestinal Inflammation and Intestinal Barrier Permeability Are Elevated in Parkinson’s Disease, Front. Neurosci. source

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    • cites [134] Mulak, 2019, Fecal Calprotectin as a Marker of the Gut Immune System Activation Is Elevated in Parkinson’s Disease, Front. Neurosci. source

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    Premisecitation

    In plasma, higher levels of acetate, propionate and butyrate are found in Parkinson's disease patients compared to controls, with plasma butyrate and valerate inversely correlated with MMSE scores.

    “In plasma, Chen et al. report higher levels of acetate, propionate and butyrate in PD patients compared to controls, with plasma butyrate and valerate being inversely correlated with MMSE scores [62]”
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    • cites [62] Chen, 2022, Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease, Neurology source

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    Interpretationcitation

    Akkermansia muciniphila's mucin degrading activity might damage the gut-barrier, triggering inflammation and promoting gut permeability.

    “its mucin degrading activity might also damage the gut-barrier triggering inflammation and promoting gut permeability [83,84]”
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    • cites [83] Jangi, 2016, Alterations of the Human Gut Microbiome in Multiple Sclerosis, Nat. Commun. source

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    • cites [84] Ganesh, B.P., Klopfleisch, R., Loh, G., and Blaut, M. (2013). Commensal Akkermansia Muciniphila Exacerbates Gut Inflammation in Salmonella Typhimurium-Infected Gnotobiotic Mice. PLoS ONE, 8. source

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    Interpretationcitation

    A high abundance of Akkermansia muciniphila may accelerate disease progression and favor α-synuclein aggregation in gut enteroendocrine cells.

    “Therefore, a high abundance of Akkermansia muciniphila may accelerate disease progression and favor α-synuclein (the already mentioned crucial protein involved in PD pathology) aggregation in gut enteroendocrine cells [85]”
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    • cites [85] Bosque, 2022, Akkermansia Muciniphila Induces Mitochondrial Calcium Overload and α -Synuclein Aggregation in an Enteroendocrine Cell Line, iScience source

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    Premisecitation

    In Parkinson's disease, a decrease in branched chain and aromatic amino acid biosynthesis, carbohydrate fermentation and butyrate synthesis is accompanied by an upregulation in LPS production, bacterial type III secretion system biosynthesis and proteolytic fermentation, which trigger inflammation and promote the release of harmful metabolites such as phenylacetylglutamine and p-cresol.

    “Studies show that a decrease in branched chain and aromatic amino acid biosynthesis, carbohydrate fermentation and butyrate synthesis is accompanied by an upregulation in lipopolysaccharides (LPS) production, bacterial type III secretion system biosynthesis (a complex bacterial structure involved in virulence) and proteolytic fermentation, which trigger inflammation and promote the release of”
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    • cites [50] Keshavarzian, 2015, Colonic Bacterial Composition in Parkinson’s Disease, Mov. Disord. source

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    • cites [101] Cirstea, 2020, Microbiota Composition and Metabolism Are Associated With Gut Function in Parkinson’s Disease, Mov. Disord. source

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    • cites [102] Yan, 2021, Alterations of Gut Microbiota and Metabolome with Parkinson’s Disease, Microb Pathog. source

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    Premisecitation

    Low levels of acetate, butyrate and above all propionate in feces from Parkinson's disease patients are linked to worse MDS-UPDRS part III scores, and the same is true for serum propionic acid.

    “It has been shown that low levels of acetate, butyrate and above all propionate in feces from PD patients are linked to worse MDS-UPDRS part III scores [62,109], and the same is true for serum propionic acid [110]”
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    • cites [62] Chen, 2022, Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease, Neurology source

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    • cites [109] Huang, 2021, The Gut Microbiota Metabolite Propionate Ameliorates Intestinal Epithelial Barrier Dysfunction-Mediated Parkinson’s Disease via the AKT Signaling Pathway, Neuroreport source

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    • cites [110] Wu, G., Jiang, Z., Pu, Y., Chen, S., Wang, T., Wang, Y., Xu, X., Wang, S., Jin, M., and Yao, Y. (2022). Serum Short-Chain Fatty Acids and Its Correlation with Motor and Non-Motor Symptoms in Parkinson’s Disease Patients. BMC Neurol., 22. source

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    Premisecitation

    Propionate supplementation was able to promote neurite outgrowth, tyrosine hydroxylase expression and dopaminergic cell survival in vitro.

    “propionate supplementation was able to promote neurite outgrowth, tyrosine hydroxylase (TH) expression and dopaminergic cell survival in vitro [112]”
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    • cites [112] Ostendorf, F., Metzdorf, J., Gold, R., Haghikia, A., and Tönges, L. (2020). Propionic Acid and Fasudil as Treatment against Rotenone Toxicity in an In Vitro Model of Parkinson’s Disease. Molecules, 25. source

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    Premisecitation

    Lachnospiraceae are underrepresented in Parkinson's disease-related gut microbiomes and contribute to the maintenance of intestinal homeostasis and prevent gut inflammation through the secretion of butyrate.

    “Lachnospiraceae are another family of bacteria underrepresented in PD-related gut microbiomes that contribute to the maintenance of intestinal homeostasis and prevent gut inflammation through the secretion of butyrate [67,68,69]”
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    • cites [67] Landskron, 2019, Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases, Front. Immunol. source

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    • cites [68] Lin, 2018, Gut Microbiota in Patients with Parkinson’s Disease in Southern China, Park. Relat. Disord. source

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    • cites [69] Barichella, 2019, Unraveling Gut Microbiota in Parkinson’s Disease and Atypical Parkinsonism, Mov. Disord. source

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    Premisecitation

    Lower levels of butyrate are linked to postural instability, gait disorders, MDS-UPDRS part III motor scores and depression among Parkinson's disease patients showing a reduced count of Faecalibacterium.

    “lower levels of butyrate are linked to postural instability, gait disorders, Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III motor scores and depression among PD patients showing a reduced count of Faecalibacterium [59,60,61,62,63]”
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    • cites [59] Meixner, 2020, Changes in Gastrointestinal Microbiome Composition in PD: A Pivotal Role of Covariates, Front. Neurol. source

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    • cites [60] Xie, 2022, Bacterial Butyrate in Parkinson’s Disease Is Linked to Epigenetic Changes and Depressive Symptoms, Mov. Disord. source

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    • cites [61] Tan, 2021, Gut Microbial Ecosystem in Parkinson Disease: New Clinicobiological Insights from Multi-Omics, Ann. Neurol. source

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    • cites [62] Chen, 2022, Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease, Neurology source

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    • cites [63] Li, 2017, Structural Changes of Gut Microbiota in Parkinson’s Disease and Its Correlation with Clinical Features, Sci. China Life Sci. source

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    Premisecitation

    Serum from Parkinson's disease patients contains low levels of LPS binding protein, indicative of a chronic systemic exposure to LPS and gram-negative endobacteria.

    “serum from PD patients contains low levels of LPS binding protein [145,146], which are indicative of a chronic systemic exposure to LPS and gram negative endobacteria [147,148,149]”
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    • cites [145] Hasegawa, S., Goto, S., Tsuji, H., Okuno, T., Asahara, T., Nomoto, K., Shibata, A., Fujisawa, Y., Minato, T., and Okamoto, A. (2015). Intestinal Dysbiosis and Lowered Serum Lipopolysaccharide-Binding Protein in Parkinson’s Disease. PLoS ONE, 10. source

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    • cites [146] Forsyth, C.B., Shannon, K.M., Kordower, J.H., Voigt, R.M., Shaikh, M., Jaglin, J.A., Estes, J.D., Dodiya, H.B., and Keshavarzian, A. (2011). Increased Intestinal Permeability Correlates with Sigmoid Mucosa Alpha-Synuclein Staining and Endotoxin Exposure Markers in Early Parkinson’s Disease. PLoS ONE, 6. source

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    • cites [147] Pal, 2015, Abnormal Lipopolysaccharide Binding Protein as Marker of Gastrointestinal Inflammation in Parkinson Disease, Front. Neurosci. source

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    • cites [148] Gutsmann, 2001, Dual Role of Lipopolysaccharide (LPS)-Binding Protein in Neutralization of LPS and Enhancement of LPS-Induced Activation of Mononuclear Cells, Infect Immun. source

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    • cites [149] Minter, 2009, LPS-Binding Protein Mediates LPS-Induced Liver Injury and Mortality in the Setting of Biliary Obstruction, Am. J. Physiol.-Gastrointest. Liver Physiol. source

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    Premisecitation

    Patients receiving an L-dopa + carbidopa intestinal gel display higher levels of Enterobacteriaceae, Escherichia and Serratia compared to those receiving only L-dopa, while both groups show metabolic markers of gut inflammation.

    “patients receiving an L-dopa + carbidopa intestinal gel display higher levels of Enterobacteriaceae, Escherichia and Serratia compared to those receiving only L-dopa, while both groups show metabolic markers of gut inflammation [186]”
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    Premisecitation

    In the intestine, L-dopa is first transformed into dopamine by a dopa decarboxylase from E. faecalis and then converted into m-tyramine through the action of a dehydroxylase from Eggerthella lenta.

    “in the intestine, L-dopa is first transformed into dopamine by a dopa decarboxylase from E. faecalis and then converted into m-tyramine through the action of a dehydroxylase from Eggerthella lenta [181,182,183]”
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    • cites [181] Bess, 2019, Discovery and Inhibition of an Interspecies Gut Bacterial Pathway for Levodopa Metabolism, Science (1979)

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    Premisecitation

    Simultaneous measurement of Blautia levels in feces, brain and blood can be used to differentiate cases from controls, as Parkinson's disease patients show reduced abundance of this genus.

    “Guo et al. reported that the simultaneous measurement of Blautia levels in the feces, brain and blood can be used to differentiate cases from controls, as PD patients show reduced abundance of this genus [162]”
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    • cites [162] Guo, X., Tang, P., Hou, C., Chong, L., Zhang, X., Liu, P., Chen, L., Liu, Y., Zhang, L., and Li, R. (2022). Integrated Microbiome and Host Transcriptome Profiles Link Parkinson’s Disease to Blautia Genus: Evidence From Feces, Blood, and Brain. Front. Microbiol., 13. source

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    Premisecitation

    COMT inhibitors and anticholinergics are known to induce gastrointestinal side effects, which may be due to an imbalance of the intestinal flora towards harmful bacteria.

    “COMT inhibitors and anticholinergics are known to induce GI side effects [192,193,194], which may be due to an imbalance of the intestinal flora towards harmful bacteria [190]”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [192] Gray, 2022, Long-Term Effectiveness of Adjuvant Treatment With Catechol-O-Methyltransferase or Monoamine Oxidase B Inhibitors Compared With Dopamine Agonists Among Patients With Parkinson Disease Uncontrolled by Levodopa Therapy, JAMA Neurol. source

      Not checked in the free run.

    • cites [193] Ness, 2006, Anticholinergic Medications in Community-Dwelling Older Veterans: Prevalence of Anticholinergic Symptoms, Symptom Burden, and Adverse Drug Events, Am. J. Geriatr. Pharm. source

      Not checked in the free run.

    • cites [194] Kaakkola, 2000, Clinical Pharmacology, Therapeutic Use and Potential of COMT Inhibitors in Parkinson’s Disease, Drugs source

      Not checked in the free run.

    • cites [190] Chen, 2021, Association of Parkinson’s Disease With Microbes and Microbiological Therapy, Front. Cell Infect. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A combination of 25 genetic microbial markers could effectively distinguish cases from controls and differentially diagnose Parkinson's disease, Alzheimer's disease and multiple system atrophy patients.

    “Qian et al. reported that a combination of 25 genetic microbial markers could effectively distinguish not only cases from controls but also differentially diagnose PD, AD and multiple system atrophy patients [157]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [157] Qian, 2020, Gut Metagenomics-Derived Genes as Potential Biomarkers of Parkinson’s Disease, Brain source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Upon oral berberine intake, the enterococcal tyrosine hydroxylase enzyme synthetizes L-dopa, which is then converted to dopamine in the brain, thus improving cognitive symptoms.

    “upon oral berberine intake, the enterococcal TH enzyme synthetizes L-dopa, which is then converted to dopamine in the brain, thus improving cognitive symptoms [204]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [204] Wang, 2021, Oral Berberine Improves Brain Dopa/Dopamine Levels to Ameliorate Parkinson’s Disease by Regulating Gut Microbiota, Signal Transduct Target Ther. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Carbidopa is not effective against bacterial dopa decarboxylases, enabling the gut microbiota to metabolize L-dopa, decreasing drug availability while increasing side effects.

    “carbidopa is not effective against the bacterial dopa decarboxylases [180], and this enables the GM to metabolize L-dopa, decreasing the drug availability while increasing the side effects [180,181]”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [180] Frye, 2019, Gut Bacterial Tyrosine Decarboxylases Restrict Levels of Levodopa in the Treatment of Parkinson’s Disease, Nat. Commun. source

      Not checked in the free run.

    • cites [181] Bess, 2019, Discovery and Inhibition of an Interspecies Gut Bacterial Pathway for Levodopa Metabolism, Science (1979)

      Not checked in the free run.

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

    Premisecitation

    Ceftriaxone (CTX) is a β-lactam antibiotic with a strong and safe past record.

    “Ceftriaxone (CTX) is a β-lactam antibiotic with a strong and safe past record [225,226].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [225] Yimer, 2019, Repurposing of the β-Lactam Antibiotic, Ceftriaxone for Neurological Disorders: A Review, Front. Neurosci. source

      Not checked in the free run.

    • cites [226] Tai, 2019, A New Avenue for Treating Neuronal Diseases: Ceftriaxone, an Old Antibiotic Demonstrating Behavioral Neuronal Effects, Behavioural. Brain Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Lower plasma levels of acetic acid and propionic acid could discriminate multiple system atrophy and Parkinson's disease with 80% sensitivity and 91% specificity, thus enabling differential diagnosis among synucleinopathies.

    “a study conducted by He et al. on 25 multiple system atrophy, 46 PD patients and 46 controls showed that lower plasma levels of acetic acid and propionic acid could discriminate the phenotypically similar multiple system atrophy and PD with 80% sensitivity and 91% specificity, thus enabling differential diagnosis among synucleinopathies [165]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [165] He, 2021, Plasma Short-Chain Fatty Acids Differences in Multiple System Atrophy from Parkinson’s Disease, J. Park. Dis.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    H. pylori is found with higher prevalence in Parkinson's disease patients compared to healthy subjects, and binding of L-dopa to H. pylori contributes to reduced absorption of the drug, resulting in motor impairment.

    “another bacterial species that is found with higher prevalence in PD patients compared to healthy subjects is Helicobacter pylori. Interestingly, the binding of L-dopa to H. pylori contributes to the reduced absorption of the drug, resulting in motor impairment [29]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Pascale, 2020, Targeting the Microbiota in Pharmacology of Psychiatric Disorders, Pharmacol. Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Rifaximin-mediated small intestinal bacterial overgrowth eradication in Parkinson's disease patients resulted in reduced motor fluctuations without impacting on L-dopa treatment.

    “rifaximin-mediated SIBO eradication in PD patients resulted in reduced motor fluctuations without impacting on L-dopa treatment [222]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [222] Fasano, 2013, The Role of Small Intestinal Bacterial Overgrowth in Parkinson’s Disease, Mov. Disord. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Increased levels of LPS in the circulation trigger systemic inflammation and mediate blood-brain barrier destruction, allowing microbial-derived inflammatory endotoxins to enter the brain.

    “Increased levels of LPS in the circulation are known to trigger systemic inflammation and to mediate BBB destruction, which allows microbial-derived inflammatory endotoxins to also enter the brain [123,129,142]”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [123] 2020, The Link between Gut Dysbiosis and Neuroinflammation in Parkinson’s Disease, Neuroscience source

      Not checked in the free run.

    • cites [129] Pellegrini, 2022, Enteric α-Synuclein Impairs Intestinal Epithelial Barrier through Caspase-1-Inflammasome Signaling in Parkinson’s Disease before Brain Pathology, NPJ Park. Dis. source

      Not checked in the free run.

    • cites [142] Mohammad, 2021, Role of Metabolic Endotoxemia in Systemic Inflammation and Potential Interventions, Front. Immunol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Blood LPS binding protein has been shown to differentiate Parkinson's disease from controls without discriminating the disease stage; however, high variability among patients currently prevents its clinical application.

    “blood LPS binding protein, has been shown to differentiate PD from controls without discriminating the disease stage; however the high variability measured among patients currently prevents its clinical application [147]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [147] Pal, 2015, Abnormal Lipopolysaccharide Binding Protein as Marker of Gastrointestinal Inflammation in Parkinson Disease, Front. Neurosci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    LPS interacts with α-synuclein and induces its nucleation, initiating a cascade of molecular events leading to the formation of protein aggregates.

    “LPS is known to interact with α-synuclein and to induce its nucleation [143], which will initiate a cascade of molecular events, leading to the formation of protein aggregates.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [143] Bhattacharyya, 2019, Lipopolysaccharide from Gut Microbiota Modulates α-Synuclein Aggregation and Alters Its Biological Function, ACS Chem. Neurosci. source

      Not checked in the free run.

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

    Premisecitation

    A reduction of Prevotellaceae together with a rise in Akkermansia have been proposed as a possible Parkinson's disease diagnostic signature.

    “Among the bacterial features, a reduction of Prevotellaceae together with a rise in Akkermansia have been proposed as a possible PD diagnostic signature [79]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [79] Chin, 2020, A Pilot Microbiota Study in Parkinson’s Disease Patients versus Control Subjects, and Effects of FTY720 and FTY720-Mitoxy Therapies in Parkinsonian and Multiple System Atrophy Mouse Models, J. Park. Dis.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Certain antibiotics can inhibit the activity of matrix metalloproteinases and prevent mitochondria dysfunction, microglia activation, protein misfolding and α-synuclein aggregation.

    “certain antibiotics can inhibit the activity of matrix metalloproteinases and prevent mitochondria dysfunction, microglia activation, protein misfolding and α-synuclein aggregation [211,212,213,214,215]”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [211] Bortolanza, 2018, Tetracycline Repurposing in Neurodegeneration: Focus on Parkinson’s Disease, J. Neural. Transm. source

      Not checked in the free run.

    • cites [212] Yadav, 2021, Ayushi Potential of Antibiotics for the Treatment and Management of Parkinson’s Disease: An Overview, Curr. Drug Res. Rev. source

      Not checked in the free run.

    • cites [213] Hurkacz, M., Dobrek, L., and Wiela-Hojeńska, A. (2021). Antibiotics and the Nervous System—Which Face of Antibiotic Therapy Is Real, Dr. Jekyll (Neurotoxicity) or Mr. Hyde (Neuroprotection)?. Molecules, 26. source

      Not checked in the free run.

    • cites [214] Balducci, 2019, Doxycycline for Alzheimer’s Disease: Fighting β-Amyloid Oligomers and Neuroinflammation, Front. Pharmacol. source

      Not checked in the free run.

    • cites [215] Lorente-Picón, M., and Laguna, A. (2021). New Avenues for Parkinson’s Disease Therapeutics: Disease-Modifying Strategies Based on the Gut Microbiota. Biomolecules, 11. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    L-dopa exposure is associated with increased relative abundance of Peptoniphilus, Finegoldia and Enterococcus, as well as reduced presence of Faecalibacterium, Blautia and Lachnospirae.

    “an increased relative abundance of Peptoniphilus, Finegoldia and Enterococcus, as well as a reduced presence of Faecalibacterium, Blautia and Lachnospirae were reported upon L-dopa exposure [185,186]”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [185] Weis, 2019, Effect of Parkinson’s Disease and Related Medications on the Composition of the Fecal Bacterial Microbiota, NPJ Park. Dis. source

      Not checked in the free run.

    • cites [186] Melis, 2021, Gut Microbiota and Metabolome Distinctive Features in Parkinson Disease: Focus on Levodopa and Levodopa-carbidopa Intrajejunal Gel, Eur. J. Neurol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    C. sporogenes can deaminate L-dopa, originating the metabolite 3-(3,4-dihydroxyphenyl) propionic acid, which is reported to impair ileal mobility.

    “C. sporogenes can also deaminate L-dopa, originating the metabolite 3-(3,4-dihydroxyphenyl) propionic acid, which is reported to impair ileal mobility [184]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [184] van Kessel, S.P., de Jong, H.R., Winkel, S.L., van Leeuwen, S.S., Nelemans, S.A., Permentier, H., Keshavarzian, A., and el Aidy, S. (2020). Gut Bacterial Deamination of Residual Levodopa Medication for Parkinson’s Disease. BMC Biol., 18. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CTX reduces TLR-4, MyD88, and NF-κB in the colon.

    “Further studies proved the ability of CTX to reduce the levels of the main pro-inflammatory mediators TLR-4, MyD88 (myeloid differentiation primary response 88), IL-1β, TNF-α and NF-κB in the brain, TLR-4, MyD88, and NF-κB in the colon and IL-1β, TNF-α and IL-6 in the serum [232,233,234].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [232] Zhou, 2021, Neuroprotective Effect of Ceftriaxone on MPTP-Induced Parkinson’s Disease Mouse Model by Regulating Inflammation and Intestinal Microbiota, Oxid Med. Cell. Longev. source

      Not checked in the free run.

    • cites [233] Kaur, 2017, Ceftriaxone Attenuates Glutamate-Mediated Neuro-Inflammation and Restores BDNF in MPTP Model of Parkinson’s Disease in Rats, Pathophysiology source

      Not checked in the free run.

    • cites [234] Bisht, 2014, Ceftriaxone Mediated Rescue of Nigral Oxidative Damage and Motor Deficits in MPTP Model of Parkinson’s Disease in Rats, Neurotoxicology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CTX reduces TLR-4, MyD88, IL-1β, TNF-α and NF-κB in the brain.

    “Further studies proved the ability of CTX to reduce the levels of the main pro-inflammatory mediators TLR-4, MyD88 (myeloid differentiation primary response 88), IL-1β, TNF-α and NF-κB in the brain, TLR-4, MyD88, and NF-κB in the colon and IL-1β, TNF-α and IL-6 in the serum [232,233,234].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [232] Zhou, 2021, Neuroprotective Effect of Ceftriaxone on MPTP-Induced Parkinson’s Disease Mouse Model by Regulating Inflammation and Intestinal Microbiota, Oxid Med. Cell. Longev. source

      Not checked in the free run.

    • cites [233] Kaur, 2017, Ceftriaxone Attenuates Glutamate-Mediated Neuro-Inflammation and Restores BDNF in MPTP Model of Parkinson’s Disease in Rats, Pathophysiology source

      Not checked in the free run.

    • cites [234] Bisht, 2014, Ceftriaxone Mediated Rescue of Nigral Oxidative Damage and Motor Deficits in MPTP Model of Parkinson’s Disease in Rats, Neurotoxicology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CTX reduces IL-1β, TNF-α and IL-6 in the serum.

    “Further studies proved the ability of CTX to reduce the levels of the main pro-inflammatory mediators TLR-4, MyD88 (myeloid differentiation primary response 88), IL-1β, TNF-α and NF-κB in the brain, TLR-4, MyD88, and NF-κB in the colon and IL-1β, TNF-α and IL-6 in the serum [232,233,234].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [232] Zhou, 2021, Neuroprotective Effect of Ceftriaxone on MPTP-Induced Parkinson’s Disease Mouse Model by Regulating Inflammation and Intestinal Microbiota, Oxid Med. Cell. Longev. source

      Not checked in the free run.

    • cites [233] Kaur, 2017, Ceftriaxone Attenuates Glutamate-Mediated Neuro-Inflammation and Restores BDNF in MPTP Model of Parkinson’s Disease in Rats, Pathophysiology source

      Not checked in the free run.

    • cites [234] Bisht, 2014, Ceftriaxone Mediated Rescue of Nigral Oxidative Damage and Motor Deficits in MPTP Model of Parkinson’s Disease in Rats, Neurotoxicology source

      Not checked in the free run.

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

    Premisecitation

    Minocycline is a second-generation semisynthetic tetracycline with anti-microbial, anti-apoptotic, anti-inflammatory and antioxidant properties.

    “Minocycline is a second-generation semisynthetic tetracycline with anti-microbial, anti-apoptotic, anti-inflammatory and antioxidant properties [247,248,249,250].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [247] Zarzuelo, 2013, Minocycline: Far beyond an Antibiotic, Br. J. Pharmacol. source

      Not checked in the free run.

    • cites [248] Cankaya, 2019, The Therapeutic Role of Minocycline in Parkinson’s Disease, Drugs Context source

      Not checked in the free run.

    • cites [249] Peng, 2006, Nigrostriatal Dopaminergic Neurodegeneration in the Weaver Mouse Is Mediated via Neuroinflammation and Alleviated by Minocycline Administration, J. Neurosci. source

      Not checked in the free run.

    • cites [250] Inamdar, 2012, The Protective Effect of Minocycline in a Paraquat-Induced Parkinson’s Disease Model in Drosophila Is Modified in Altered Genetic Backgrounds, Park. Dis.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    DOX reduces size and load of α-synuclein oligomers by converting them into high-molecular weight species that cannot form fibrils, increasing cell viability.

    “Of note, recent studies demonstrated that DOX reduces the size and load of α-synuclein oligomers by converting them into high-molecular weight species that are not able to form fibrils, thus increasing cell viability [282,284].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [282] Parrales, 2021, Doxycycline Inhibits α-Synuclein-Associated Pathologies in Vitro and in Vivo, Neurobiol. Dis. source

      Not checked in the free run.

    • cites [284] Barbosa, 2017, Repurposing Doxycycline for Synucleinopathies: Remodelling of α-Synuclein Oligomers towards Non-Toxic Parallel Beta-Sheet Structured Species, Sci. Rep. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A phase II clinical trial shows no benefit from minocycline and decreased tolerability.

    “Moreover, results from a phase II clinical trial show no benefit from the use of minocycline and evidence decreased tolerability, although more studies are needed before drawing premature conclusions [277,278].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [277] NINDS NET-PD Investigators (2008). A Pilot Clinical Trial of Creatine and Minocycline in Early Parkinson Disease. Clin. Neuropharmacol, 31, 141–150. source

      Not checked in the free run.

    • cites [278] NINDS NET-PD Investigators (2006). A Randomized, Double-Blind, Futility Clinical Trial of Creatine and Minocycline in Early Parkinson Disease. Neurology, 66, 664–671. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Doxycycline (DOX) is a broad-spectrum antibiotic belonging to tetracyclines that has been considered as PD treatment.

    “Doxycycline (DOX) is another broad-spectrum antibiotic belonging to tetracyclines that has been considered as PD treatment [279].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [279] Rahmani, 2022, The Potential Use of Tetracyclines in Neurodegenerative Diseases and the Role of Nano-Based Drug Delivery Systems, Eur. J. Pharm. Sci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    DOX inhibits production of ROS, nitric oxide, iNOS, COX-2, IL-1β and TNF-α.

    “In vitro, DOX has shown anti-inflammatory properties by interfering with p38 MAP kinase and NF-κB pathways, reducing the expression of the activated microglia marker IBA-1 and inhibiting the production of the pro-oxidant and pro-inflammatory factors ROS, nitric oxide, iNOS, cyclooxygenase-2 (COX-2), IL-1β and TNF-α [280,281,282].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [280] Socias, 2016, Doxycycline Suppresses Microglial Activation by Inhibiting the P38 MAPK and NF-KB Signaling Pathways, Neurotox. Res. source

      Not checked in the free run.

    • cites [281] Cho, 2009, Doxycycline Is Neuroprotective Against Nigral Dopaminergic Degeneration by a Dual Mechanism Involving MMP-3, Neurotox. Res. source

      Not checked in the free run.

    • cites [282] Parrales, 2021, Doxycycline Inhibits α-Synuclein-Associated Pathologies in Vitro and in Vivo, Neurobiol. Dis. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Antibiotics can kill specific microbial populations leading to intestinal dysbiosis and neurological dysfunction.

    “Generally, although promising, two main concerns remain about the use of antibiotics in PD treatment: (i) antibiotics can kill some specific microbial populations leading to intestinal dysbiosis and neurological dysfunction and (ii) their prolonged and widespread intake would favor antibiotic resistance [213,300,301].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [213] Hurkacz, M., Dobrek, L., and Wiela-Hojeńska, A. (2021). Antibiotics and the Nervous System—Which Face of Antibiotic Therapy Is Real, Dr. Jekyll (Neurotoxicity) or Mr. Hyde (Neuroprotection)?. Molecules, 26. source

      Not checked in the free run.

    • cites [300] Modi, 2014, Antibiotics and the Gut Microbiota, J. Clin. Investig. source

      Not checked in the free run.

    • cites [301] Markulin, 2022, Challenges of Repurposing Tetracyclines for the Treatment of Alzheimer’s and Parkinson’s Disease, J. Neural. Transm. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisecitation

    A probiotic fermented milk drink containing L. acidophilus, L. casei, B. bifidum, and L. fermentum improves cognitive function in AD patients.

    “while the assumption of a probiotic fermented milk drink containing L. acidophilus, L. casei, B. bifidum, and L. fermentum improves cognitive function in AD patients [323].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [323] Akbari, 2016, Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer’s Disease: A Randomized, Double-Blind and Controlled Trial, Front. Aging Neurosci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    MPTP-induced PD mice treated with rifampicin show increased striatal and SN TH immunoreactivity, attenuated oxidative stress, and re-established dopaminergic signaling in the striatum.

    “In vivo, MPTP-induced PD mice treated with rifampicin showed increased striatal and SN TH immunoreactivity, attenuated levels of oxidative stress and re-established dopaminergic signaling in the striatum [298].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [298] Oida, 2006, Rifampicin Attenuates the MPTP-Induced Neurotoxicity in Mouse Brain, Brain Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Rifampicin is a macrocyclic antibiotic with cytoprotective functions considered for PD treatment.

    “Rifampicin is a macrocyclic antibiotic with cytoprotective functions that have been considered for PD treatment [288,289].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [288] Bi, 2013, Rifampicin and Parkinson’s Disease, Neurol. Sci. source

      Not checked in the free run.

    • cites [289] Yulug, 2014, Rifampicin: An Antibiotic with Brain Protective Function, Brain Res. Bull source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Treatment with Symprove changes bacterial composition (increase Firmicutes, decrease Bacteroidetes), stimulates SCFAs and lactate, modulates mucosal inflammation (increase IL-6, IL-10, decrease IL-8), and improves intestinal permeability.

    “Ghyselinck et al. found that the treatment with this multi-strain probiotic can change the bacterial composition (increase in Firmicutes and decrease in Bacteroidetes), stimulate the production of SCFAs and lactate, modulate mucosal inflammation (by increasing anti-inflammatory cytokines such as IL-6, IL-10 and decreasing the pro-inflammatory chemokine IL-8), and improve intestinal permeability [”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [329] Ghyselinck, 2021, Influence of Probiotic Bacteria on Gut Microbiota Composition and Gut Wall Function in an In-Vitro Model in Patients with Parkinson’s Disease, Int. J. Pharm. X

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In vivo, DOX limits dopaminergic neuronal loss in SN and increases striatal dopamine levels.

    “When tested in vivo, DOX confirmed its neuroprotective activity by limiting dopaminergic neuronal loss in SN while increasing striatal dopamine levels [285,286].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [285] Lazzarini, 2013, del Doxycycline Restrains Glia and Confers Neuroprotection in a 6-OHDA Parkinson Model, Glia source

      Not checked in the free run.

    • cites [286] Zhang, 2015, A Study on the Protective Role of Doxycycline upon Dopaminergic Neuron of LPS-PD Rat Model Rat, Eur. Rev. Med. Pharmacol. Sci.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Rifampicin prevents α-synuclein fibrillation by promoting SUMOylation, increasing fibril solubility and preventing neuronal death.

    “Indeed, there is evidence that rifampicin prevents α-synuclein fibrillation by promoting SUMOylation, which increases fibril solubility preventing neuronal death [290,291,292].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [290] Lin, 2017, Rifampicin Pre-Treatment Inhibits the Toxicity of Rotenone-Induced PC12 Cells by Enhancing Sumoylation Modification of α-Synuclein, Biochem. Biophys. Res. Commun. source

      Not checked in the free run.

    • cites [291] Li, 2004, Rifampicin Inhibits α-Synuclein Fibrillation and Disaggregates Fibrils, Chem. Biol. source

      Not checked in the free run.

    • cites [292] Xu, 2007, Rifampicin Protects PC12 Cells against MPP+-Induced Apoptosis and Inhibits the Expression of an α-Synuclein Multimer, Brain Res. source

      Not checked in the free run.

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

    Premisecitation

    The probiotic SLAB51 improves cognition and reduces amyloid plaques, brain injury, and inflammatory cytokine plasma levels in AD mice.

    “further, the probiotic SLAB51, a formulation of nine live bacterial strains (Streptococcus thermophilus, B. longum, B. breve, B. infantis, L. acidophilus, L. plantarum, L. paracasei, L. delbrueckii subsp. bulgaricus, and L. brevis) improves cognition and reduces the accumulation of amyloid plaques, brain injury, and inflammatory cytokines plasma levels in AD mice [322],”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [322] Bonfili, 2017, Microbiota Modulation Counteracts Alzheimer’s Disease Progression Influencing Neuronal Proteolysis and Gut Hormones Plasma Levels, Sci. Rep. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The most common bacteria used as probiotics (Lactobacilli, Bifidobacteria, and Enterococci) have potential benefits in restoring GM, reducing intestinal permeability, inflammation, and oxidative stress, improving immune homeostasis and GI symptoms, and preventing or counteracting several conditions.

    “It is widely reported that the most common bacteria used as probiotics (Lactobacilli, Bifidobacteria, and Enterococci) [309] have potential benefits in restoring the GM, reducing intestinal permeability, inflammation, and oxidative stress, improving immune homeostasis and GI symptoms (constipation, diarrhoea, bloating, and abdominal pain), as well as preventing or counteracting several conditions,”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [215] Lorente-Picón, M., and Laguna, A. (2021). New Avenues for Parkinson’s Disease Therapeutics: Disease-Modifying Strategies Based on the Gut Microbiota. Biomolecules, 11. source

      Not checked in the free run.

    • cites [310] Cristofori, 2021, Anti-Inflammatory and Immunomodulatory Effects of Probiotics in Gut Inflammation: A Door to the Body, Front. Immunol. source

      Not checked in the free run.

    • cites [311] Gazerani, P. (2019). Probiotics for Parkinson’s Disease. Int. J. Mol. Sci., 20. source

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    • cites [312] Gupta, 2009, PROBIOTICS, Indian J. Med. Microbiol. source

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    • cites [313] Reid, 2011, Microbiota Restoration: Natural and Supplemented Recovery of Human Microbial Communities, Nat. Rev. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    GM dysbiosis is a factor in the development of several neurological diseases, including PD, AD, multiple sclerosis, ASD, anxiety, depression, schizophrenia, and other mental illnesses.

    “Moreover, it is now evident that GM dysbiosis is a factor that takes part in the development of several neurological diseases, including PD, AD, multiple sclerosis, autism spectrum disorders (ASD), anxiety, depression, schizophrenia, and other mental illnesses [314,315].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [314] Nandwana, V., Nandwana, N.K., Das, Y., Saito, M., Panda, T., Das, S., Almaguel, F., Hosmane, N.S., and Das, B.C. (2022). The Role of Microbiome in Brain Development and Neurodegenerative Diseases. Molecules, 27. source

      Not checked in the free run.

    • cites [315] Peterson, 2020, Dysfunction of the Microbiota-Gut-Brain Axis in Neurodegenerative Disease: The Promise of Therapeutic Modulation With Prebiotics, Medicinal Herbs, Probiotics, and Synbiotics, J. Evid Based Integr. Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Probiotic intake can reduce neuroinflammation, inhibit loss of dopaminergic neurons, and modulate brain functions in PD.

    “Concerning PD, many studies showed that probiotic intake can reduce neuroinflammation, inhibit the loss of dopaminergic neurons, and modulate brain functions, as explained in the sections that follow [324,325,326,327].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [324] Abildgaard, 2017, Probiotic Treatment Reduces Depressive-like Behaviour in Rats Independently of Diet, Psychoneuroendocrinology source

      Not checked in the free run.

    • cites [325] Srivastav, 2019, Probiotics Mixture Increases Butyrate, and Subsequently Rescues the Nigral Dopaminergic Neurons from MPTP and Rotenone-Induced Neurotoxicity, J. Nutr. Biochem. source

      Not checked in the free run.

    • cites [326] Wallace, C.J.K., and Milev, R. (2017). The Effects of Probiotics on Depressive Symptoms in Humans: A Systematic Review. Ann. Gen. Psychiatry, 16. source

      Not checked in the free run.

    • cites [327] Wang, 2016, Effect of Probiotics on Central Nervous System Functions in Animals and Humans: A Systematic Review, J. Neurogastroenterol. Motil. source

      Not checked in the free run.

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

    Premisecitation

    Bacteroides fragilis improves ASD symptoms and gut barrier integrity, and reduces intestinal permeability.

    “For instance, Bacteroides fragilis has been documented to improve ASD symptoms and gut barrier integrity, and reduce intestinal permeability [321];”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [321] Hsiao, 2013, Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders, Cell source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ceftriaxone-induced dysbiosis worsens motor symptoms in 6-OHDA treated mice and correlates with dopaminergic neuron toxicity and intestinal and systemic inflammation.

    “There is evidence that ceftriaxone (a third-generation cephalosporin)-induced dysbiosis worsens motor symptoms in 6-OHDA treated mice and correlates with dopaminergic neuron toxicity as well as intestinal and systemic inflammation [302].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [302] Avagliano, C., Coretti, L., Lama, A., Pirozzi, C., de Caro, C., de Biase, D., Turco, L., Mollica, M.P., Paciello, O., and Calignano, A. (2022). Dual-Hit Model of Parkinson’s Disease: Impact of Dysbiosis on 6-Hydroxydopamine-Insulted Mice—Neuroprotective and Anti-Inflammatory Effects of Butyrate. Int. J. Mol. Sci., 23. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    DOX contrasts glial reactivity and reduces MHC-II expression in microglial cells.

    “This beneficial function is achieved by contrasting glial reactivity and by reducing the major histocompatibility complex-II expression in microglial cells [285,286].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [285] Lazzarini, 2013, del Doxycycline Restrains Glia and Confers Neuroprotection in a 6-OHDA Parkinson Model, Glia source

      Not checked in the free run.

    • cites [286] Zhang, 2015, A Study on the Protective Role of Doxycycline upon Dopaminergic Neuron of LPS-PD Rat Model Rat, Eur. Rev. Med. Pharmacol. Sci.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    FMT re-establishes eubiosis by disadvantaging growth of Desulfovibrio, Akkermansia and Proteobacteria (orders Enterobacteriales and Turicibacteriales), while favoring proliferation of Bacteroidetes and Actinobacteria phyla, particularly Blautia and Prevotella species.

    “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”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [469] Sun, 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. source

      Not checked in the free run.

    • cites [470] Zhao, 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 source

      Not checked in the free run.

    • cites [472] Zhang, 2021, Gut Microbiota Relieves Inflammation in the Substantia Nigra of Chronic Parkinson’s Disease by Protecting the Function of Dopamine Neurons, Exp. Ther. Med. source

      Not checked in the free run.

    • Rests on an assumption: Findings from animal models of FMT in PD can be extrapolated to human PD patients.

  • May combine two claims.

    Premisecitation

    In a clinical study, supplementation of PD patients with ω3 had a favorable effect on glutathione concentrations and total antioxidant capacity, and was associated with a lower amount of C-reactive protein.

    “Indeed, a clinical study found that supplementation of PD patients with ω3 has a favorable effect on glutathione concentrations, as well as on the total antioxidant capacity, and it is associated with a lower amount of C-reactive protein [458].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [458] Taghizadeh, 2017, The Effects of Omega-3 Fatty Acids and Vitamin E Co-Supplementation on Clinical and Metabolic Status in Patients with Parkinson’s Disease: A Randomized, Double-Blind, Placebo-Controlled Trial, Neurochem. Int. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ω3 are able to ameliorate oxidative stress and neuroinflammation, which may explain part of their beneficial effects on PD.

    “Within this context, ω3 are able to ameliorate oxidative stress and neuroinflammation, which may explain part of their beneficial effects on PD [457].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [457] Teleanu, D.M., Niculescu, A.-G., Lungu, I.I., Radu, C.I., Vladâcenco, O., Roza, E., Costăchescu, B., Grumezescu, A.M., and Teleanu, R.I. (2022). An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases. Int. J. Mol. Sci., 23. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Fecal matter transplantation from healthy mice to PD recipient mice improved physical performance, ameliorated motor symptoms and reduced dysbiosis in several independent studies.

    “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].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [469] Sun, 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. source

      Not checked in the free run.

    • cites [470] Zhao, 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 source

      Not checked in the free run.

    • cites [471] Zhong, 2021, 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, Neurochem. Res. source

      Not checked in the free run.

    • cites [472] Zhang, 2021, Gut Microbiota Relieves Inflammation in the Substantia Nigra of Chronic Parkinson’s Disease by Protecting the Function of Dopamine Neurons, Exp. Ther. Med. source

      Not checked in the free run.

    • Rests on an assumption: Findings from animal models of FMT in PD can be extrapolated to human PD patients.

  • May combine two claims.

    Premisecitation

    Fecal microbiota transfer from PD mice to healthy counterparts increases motor deficits while reducing striatal levels of dopamine, serotonin and their metabolites, reproducing typical features of the disease.

    “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].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [469] Sun, 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. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    FMT appears to protect from gut inflammation by promoting intestinal barrier integrity and reducing LPS levels in the colon, serum, and SN, preventing leaky gut and systemic inflammation.

    “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].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [470] Zhao, 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 source

      Not checked in the free run.

    • Rests on an assumption: Findings from animal models of FMT in PD can be extrapolated to human PD patients.

  • May combine two claims.

    Premisecitation

    Experimental evidence supports that ω3-PUFAs reduce NOS activity and increase BDNF levels in the CNS.

    “These findings are supported by experimental evidence that ω3-PUFAs reduce NOS activity and increase BDNF levels in the CNS [459,460].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [459] Cardoso, 2014, Omega-3 Deficiency and Neurodegeneration in the Substantia Nigra: Involvement of Increased Nitric Oxide Production and Reduced BDNF Expression, Biochim. Et Biophys. Acta (BBA)-Gen. Subj. source

      Not checked in the free run.

    • cites [460] Mori, 2018, Neuroprotective Effect of Omega-3 Polyunsaturated Fatty Acids in the 6-OHDA Model of Parkinson’s Disease Is Mediated by a Reduction of Inducible Nitric Oxide Synthase, Nutr. Neurosci. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Addition of ω3 to the diet of PD patients may be a valuable approach to reduce depression symptoms and can also impact other clinical aspects of the disease.

    “As a result, the addition of ω3 to the diet of PD patients may be a valuable approach to reduce depression symptoms, which can also impact other clinical aspects of the disease.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Elevated levels of cytokines and prostaglandins have been detected in the cerebrospinal fluid and brains of PD patients, where they may activate microglia, induce migration of microglia to SN, and release pro-inflammatory cytokines and neurotoxic molecules capable of exacerbating the disease.

    “Elevated levels of cytokines and prostaglandins have been detected in the cerebrospinal fluid and brains of PD patients where they may in turn activate the microglia, induce migration of microglia to SN, and release pro-inflammatory cytokines, as well as neurotoxic molecules capable of further exacerbating the disease [453,454,455,456].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [453] Subramaniam, 2017, Targeting Microglial Activation States as a Therapeutic Avenue in Parkinson’s Disease, Front. Aging Neurosci. source

      Not checked in the free run.

    • cites [454] Wijeyekoon, 2020, Cerebrospinal Fluid Cytokines and Neurodegeneration-Associated Proteins in Parkinson’s Disease, Mov. Disord. source

      Not checked in the free run.

    • cites [455] Tansey, 2010, Neuroinflammation in Parkinson’s Disease: Its Role in Neuronal Death and Implications for Therapeutic Intervention, Neurobiol. Dis. source

      Not checked in the free run.

    • cites [456] Hirsch, 2009, Neuroinflammation in Parkinson’s Disease: A Target for Neuroprotection?, Lancet Neurol. source

      Not checked in the free run.

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

    Premisecitation

    Omega-3 PUFAs are involved in inflammatory and immunological processes, as well as in hormonal regulation.

    “They are involved in inflammatory and immunological processes, as well as in hormonal regulation [440,441].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [440] Calder, 2010, Omega-3 Fatty Acids and Inflammatory Processes, Nutrients source

      Not checked in the free run.

    • cites [441] Avallone, R., Vitale, G., and Bertolotti, M. (2019). Omega-3 Fatty Acids and Neurodegenerative Diseases: New Evidence in Clinical Trials. Int. J. Mol. Sci., 20. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    FMT contrasts cognitive damage by decreasing α-synuclein expression and restoring optimal levels of striatal dopamine and serotonin, supporting neuroprotection.

    “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].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [469] Sun, 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. source

      Not checked in the free run.

    • cites [471] Zhong, 2021, 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, Neurochem. Res. source

      Not checked in the free run.

    • cites [473] Zhou, 2019, Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson’s Disease Mice via Gut Microbiota and Metabolites, Neurotherapeutics source

      Not checked in the free run.

    • Rests on an assumption: Findings from animal models of FMT in PD can be extrapolated to human PD patients.

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

    Premisecitation

    Omega-3 PUFAs, including DHA, EPA, and ALA, play a crucial role in maintaining the structure and healthy function of different organs.

    “Omega-3 (ω3) polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid [DHA, 22:6 (n-3)], eicosapentaenoic acid [EPA, 20:5(n-3)], and α-linolenic acid [ALA, 18:3 (n-3)], play a crucial role in maintaining the structure and healthy function of different organs.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [440] Calder, 2010, Omega-3 Fatty Acids and Inflammatory Processes, Nutrients source

      Not checked in the free run.

    • cites [441] Avallone, R., Vitale, G., and Bertolotti, M. (2019). Omega-3 Fatty Acids and Neurodegenerative Diseases: New Evidence in Clinical Trials. Int. J. Mol. Sci., 20. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Consistent preclinical studies and a handful of human case reports have shown that FMT might reduce motor and non-motor symptoms, as well as constipation, in PD at least in the short term.

    “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).”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [40] Sampson, 2016, Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease, Cell source

      Not checked in the free run.

    • cites [465] Vendrik, 2020, Fecal Microbiota Transplantation in Neurological Disorders, Front. Cell. Infect Microbiol. source

      Not checked in the free run.

    • cites [469] Sun, 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. source

      Not checked in the free run.

    • cites [470] Zhao, 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 source

      Not checked in the free run.

    • cites [471] Zhong, 2021, 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, Neurochem. Res. source

      Not checked in the free run.

    • cites [472] Zhang, 2021, Gut Microbiota Relieves Inflammation in the Substantia Nigra of Chronic Parkinson’s Disease by Protecting the Function of Dopamine Neurons, Exp. Ther. Med. source

      Not checked in the free run.

    • cites [473] Zhou, 2019, Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson’s Disease Mice via Gut Microbiota and Metabolites, Neurotherapeutics source

      Not checked in the free run.

    • cites [474] Huang, 2019, Fecal Microbiota Transplantation to Treat Parkinson’s Disease with Constipation, Medicine source

      Not checked in the free run.

    • cites [475] Kuai, 2021, Evaluation of Fecal Microbiota Transplantation in Parkinson’s Disease Patients with Constipation, Microb. Cell. Fact source

      Not checked in the free run.

    • cites [476] Xue, 2020, Fecal Microbiota Transplantation Therapy for Parkinson’s Disease, Medicine source

      Not checked in the free run.

    • Rests on an assumption: Findings from animal models of FMT in PD can be extrapolated to human PD patients.

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

    Premisecitation

    PD, like other neurodegenerative diseases, is associated with oxidative stress and inflammation pathways that are tightly linked and interdependent.

    “As mentioned, PD, like other neurodegenerative diseases, is associated with oxidative stress and inflammation pathways, which are tightly linked and interdependent [452].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [452] Kujawska, 2021, Editorial: Common Pathways Linking Neurodegenerative Diseases—The Role of Inflammation, Front. Cell. Neurosci. source

      Not checked in the free run.

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

    Premisecitation

    Depression affects over 40% of PD cases.

    “Besides the motor symptoms, depression affects over 40% of PD cases [445].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [445] Reijnders, 2008, A Systematic Review of Prevalence Studies of Depression in Parkinson’s Disease, Mov. Disord. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Some limited human studies have shown that consuming PUFAs, including through diets such as MD or KD, and specifically EPA and DHA supplementation, may reduce the risk of PD and relieve some motor symptoms.

    “Some limited human studies have shown that consuming PUFAs, being components of different diets such as MD or KD, and specifically the supplementation with EPA and DHA may reduce the risk of PD and relieve some of its symptoms like motor symptoms [442,443,444].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [442] Bornebroek, 2005, Dietary Fatty Acids and the Risk of Parkinson Disease, Neurology source

      Not checked in the free run.

    • cites [443] Abbott, 2003, Environmental, Life-Style, and Physical Precursors of Clinical Parkinson?S Disease: Recent Findings from the Honolulu-Asia Aging Study, J. Neurol. source

      Not checked in the free run.

    • cites [444] Pantzaris, 2021, Neuroaspis PLP10TM, a Nutritional Formula Rich in Omega-3 and Omega-6 Fatty Acids with Antioxidant Vitamins Including Gamma-Tocopherol in Early Parkinson’s Disease: A Randomized, Double-Blind, Placebo-Controlled Trial, Clin. Neurol. Neurosurg. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Differences in geography, diet and lifestyle can greatly influence GM composition, and host genetics may play a major role.

    “In addition, it is known that differences in geography, diet and lifestyle can greatly influence the GM composition [91,508,509], and host genetics may play a major role [510].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [91] Porras, 2021, Geographic Differences in Gut Microbiota Composition Impact Susceptibility to Enteric Infection, Cell Rep. source

      Not checked in the free run.

    • cites [508] Conlon, 2014, The Impact of Diet and Lifestyle on Gut Microbiota and Human Health, Nutrients source

      Not checked in the free run.

    • cites [509] Aslam, 2020, The Effects of Dairy and Dairy Derivatives on the Gut Microbiota: A Systematic Literature Review, Gut Microbes source

      Not checked in the free run.

    • cites [510] Amato, 2021, Host Genetics Influence the Gut Microbiome, Science (1979)

      Not checked in the free run.

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

    Premisecitation

    Alterations in abundance of oral bacteria have been directly or indirectly linked to onset of cancer, cardiovascular and pulmonary diseases, stroke, diabetes and neurodegeneration.

    “Accordingly, alterations in the abundance of oral bacteria have been directly or indirectly linked to the onset of different disorders, such as cancer, cardiovascular and pulmonary diseases, stroke, diabetes and even neurodegeneration [487,488,489,490,491].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [487] Singh, 2019, Gastro-Intestinal and Oral Microbiome Signatures Associated with Healthy Aging, Geroscience source

      Not checked in the free run.

    • cites [488] Irfan, 2020, The Oral Microbiome and Cancer, Front. Immunol. source

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    • cites [489] Hayes, 2018, Association of Oral Microbiome With Risk for Incident Head and Neck Squamous Cell Cancer, JAMA Oncol. source

      Not checked in the free run.

    • cites [490] Pathak, 2021, The Role of Oral Microbiome in Respiratory Health and Diseases, Respir. Med. source

      Not checked in the free run.

    • cites [491] Sureda, 2020, Oral Microbiota and Alzheimer’s Disease: Do All Roads Lead to Rome?, Pharmacol. Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mice receiving Porphyromonas gingivalis showed sustained colon TNF-α and IL-1β expression, higher serum IL-17A and its receptor in brain, associated with loss of dopaminergic neurons, α-synuclein accumulation and microglia activation.

    “Moreover, mice receiving Porphyromonas gingivalis, a pathogen associated with chronic periodontitis, showed sustained colon TNF-α and IL-1β expression, as well as higher levels of serum IL-17A and its receptor (IL-17AR) in the brain, which were associated with loss of dopaminergic neurons, α -synuclein accumulation and microglia activation [502].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [502] Feng, 2020, Oral P. Gingivalis Impairs Gut Permeability and Mediates Immune Responses Associated with Neurodegeneration in LRRK2 R1441G Mice, J. Neuroinflamm. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Promising evidence is emerging for an association between oral/nasal microbiota and PD, but data remain limited and sometimes conflicting.

    “Overall, promising evidence is emerging for an association between oral/nasal microbiota and PD, but data remain limited and sometimes conflicting.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Combined oral-gut microbiome metagenomic sequencing revealed a link between oral Lactobacillus and gut opportunistic pathogens, suggesting a connection between these two microbial communities.

    “Moreover, combined oral-gut microbiome metagenomic sequencing revealed a link between oral Lactobacillus and gut opportunistic pathogens, suggesting a connection between these two microbial communities [498].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [498] Jo, 2022, Oral and Gut Dysbiosis Leads to Functional Alterations in Parkinson’s Disease, NPJ Park. Dis. source

      Not checked in the free run.

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

    Premisecitation

    Preliminary evidence shows that specific oral microbiota compositions are associated with human healthy aging.

    “Preliminary evidence is showing that specific oral microbiota compositions, also known as oral microbiota signatures, are associated with human healthy aging [487].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [487] Singh, 2019, Gastro-Intestinal and Oral Microbiome Signatures Associated with Healthy Aging, Geroscience source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    An increase in local pro-inflammatory molecules IL1-RA, IL-1β and TNF-α has been associated with dysbiosis in a study comparing 20 PD patients and 20 matched controls, which may contribute to onset of PD.

    “For example, an increase in different local pro-inflammatory molecules, such as IL1-RA, IL-1β and TNF-α, has been associated with dysbiosis in a study comparing 20 PD patients and 20 matched controls, which may contribute to the onset of PD [499].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [499] Fleury, 2021, Oral Dysbiosis and Inflammation in Parkinson’s Disease, J. Park. Dis.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Several limitations of FMT for PD remain, including standard clinical protocols, delivery methods, periodicity, donor selection criteria, patient inclusion criteria, long-term benefits and potential risks.

    “Despite the therapeutic potential of FMT for the treatment of PD, several limitations still exist and need to be addressed. Standard clinical protocols, delivery methods, periodicity, donor’s selection criteria, patient’s inclusion criteria, long-term benefits and potential risks remain an issue [463,467,481,482,483,484,485].”
    Quote in the paperSubstantial claim0 of 7 sources checked
    • cites [463] Tan, 2020, Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease: An Update, Front. Pharmacol. source

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    • cites [467] Evrensel, 2016, Fecal Microbiota Transplantation and Its Usage in Neuropsychiatric Disorders, Clin. Psychopharmacol. Neurosci. source

      Not checked in the free run.

    • cites [481] Choi, 2016, Fecal Microbiota Transplantation: Current Applications, Effectiveness, and Future Perspectives, Clin. Endosc. source

      Not checked in the free run.

    • cites [482] Schmulson, 2018, Fecal Microbiota Transfer for Bowel Disorders: Efficacy or Hype?, Curr. Opin. Pharmacol. source

      Not checked in the free run.

    • cites [483] Shanahan, 2014, Manipulation of the Microbiota for Treatment of IBS and IBD—Challenges and Controversies, Gastroenterology source

      Not checked in the free run.

    • cites [484] Lopetuso, 2020, Fecal Transplantation for Ulcerative Colitis: Current Evidence and Future Applications, Expert Opin. Biol. Ther. source

      Not checked in the free run.

    • cites [485] Wang, 2019, Fecal Microbiota Transplantation: Review and Update, J. Formos. Med. Assoc. source

      Not checked in the free run.

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

    Premisecitation

    Nasal microbiota composition, as well as oral microbiota, changes according to dietary habits, host factors, environmental conditions and even season.

    “Moreover, the nasal microbiota composition, as well as the oral one, changes according to dietary habits, host factors, environmental conditions and even the season [503,505].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [503] Pal, 2021, Deep Nasal Sinus Cavity Microbiota Dysbiosis in Parkinson’s Disease, NPJ Park. Dis. source

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    • cites [505] Chang, 2019, Longitudinal Study of the Bacterial and Fungal Microbiota in the Human Sinuses Reveals Seasonal and Annual Changes in Diversity, Sci. Rep. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In PD patients, increased oral microbial species include Actinomyces AFQC_s, Scardovia, Kingella oralis, Streptococcus mutans, Veillonella AFUJ_s, Prevotella, Firmicutes, Negativicutes; decreased include Lachnospiraceae AM420052_s, Treponema KE332528_s, Proteobacteria, Tenercutes and Pastescibacteria.

    “Other oral microbial species whose abundance has been found altered in PD patients are: Actinomyces AFQC_s, Scardovia, Kingella oralis, Streptococcus mutans, Veillonella AFUJ_s, Prevotella, Firmicutes, Negativicutes (all increased) and Lachnospiraceae AM420052_s, Treponema KE332528_s, Proteobacteria, Tenercutes and Pastescibacteria (all decreased) [499,500].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [499] Fleury, 2021, Oral Dysbiosis and Inflammation in Parkinson’s Disease, J. Park. Dis.

      Not checked in the free run.

    • cites [500] Zapała, B., Stefura, T., Milewicz, T., Wątor, J., Piwowar, M., Wójcik-Pędziwiatr, M., Doręgowska, M., Dudek, A., Jania, Z., and Rudzińska-Bar, M. (2022). The Role of the Western Diet and Oral Microbiota in Parkinson’s Disease. Nutrients, 14. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a 2019 case study, FMT in a 71-year-old male PD patient with constipation >3 years and motor symptoms for 7 years successfully promoted regular defecation, but tremor disappeared only temporarily and reappeared two months after transplant.

    “One case study conducted in 2019 by Huang et al. investigated the potential therapeutic benefit of FMT in a 71-year-old male PD patient reporting constipation (>3 years) and motor symptoms (for 7 years). While FMT successfully promoted regular defecation, tremor disappeared only temporarily and then reappeared two months after transplant [474].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [474] Huang, 2019, Fecal Microbiota Transplantation to Treat Parkinson’s Disease with Constipation, Medicine source

      Not checked in the free run.

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

    Premisecitation

    In AD, oral microbiota dysbiosis induced by alcohol consumption takes part in AD pathogenesis through modulation of eIF2, eIF4 and mTOR pathways.

    “In AD, there is evidence that oral microbiota dysbiosis induced by alcohol consumption takes part in AD pathogenesis through the modulation of eIF2, eIF4 and mTOR pathways [494].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [494] Yussof, 2020, A Meta-Analysis of the Effect of Binge Drinking on the Oral Microbiome and Its Relation to Alzheimer’s Disease, Sci. Rep. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PD patients undergoing FMT showed increased presence of Blautia and Prevotella and diminished overall abundance of Bacteroidetes, confirming efficacy in modifying GM composition.

    “In line with preclinical data, PD patients undergoing FMT showed an increased presence of Blautia and Prevotella and a diminished overall abundance of Bacteroidetes, thus confirming the efficacy of this approach in modifying the GM composition [475].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [475] Kuai, 2021, Evaluation of Fecal Microbiota Transplantation in Parkinson’s Disease Patients with Constipation, Microb. Cell. Fact source

      Not checked in the free run.

    • Rests on an assumption: Findings from animal models of FMT in PD can be extrapolated to human PD patients.

  • May combine two claims.

    Premisecitation

    Oral features associated with PD such as dysphagia, salivary pH and drooling may influence oral microbiota by altering β-diversity index and favoring growth of opportunistic oral microbes and Lactobacillus species, which may exacerbate clinical symptoms and correlate with worse Hamilton Anxiety Scale and Hamilton Depression Rating Scale scores.

    “Concerning PD, oral features associated with the disease such as dysphagia, salivary pH and drooling may influence the oral microbiota by altering the β-diversity index and favoring the growth of opportunistic oral microbes and Lactobacillus species, which may exacerbate the clinical symptoms and correlate with worse Hamilton Anxiety Scale and Hamilton Depression Rating Scale scores [70,496,497].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [70] Li, 2022, Oral, Nasal, and Gut Microbiota in Parkinson’s Disease, Neuroscience source

      Not checked in the free run.

    • cites [496] Rozas, N.S., Tribble, G.D., and Jeter, C.B. (2021). Oral Factors That Impact the Oral Microbiota in Parkinson’s Disease. Microorganisms, 9. source

      Not checked in the free run.

    • cites [497] Mihaila, D., Donegan, J., Barns, S., LaRocca, D., Du, Q., Zheng, D., Vidal, M., Neville, C., Uhlig, R., and Middleton, F.A. (2019). The Oral Microbiome of Early Stage Parkinson’s Disease and Its Relationship with Functional Measures of Motor and Non-Motor Function. PLoS ONE, 14. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    Since many inherent covariates cannot be eliminated, search for biomarkers and therapies focused on specific populations, as well as more personalized approaches, may improve consistency.

    “Since many of these inherent covariates cannot be eliminated, the search for biomarkers and therapies focused on specific populations, as well as more “personalized” approaches, may be of interest and improve consistency [511,512].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [511] Jain, 2020, The Need for Personalized Approaches to Microbiome Modulation, Front. Public Health source

      Not checked in the free run.

    • cites [512] Vandeputte, 2020, Personalized Nutrition Through The Gut Microbiota: Current Insights And Future Perspectives, Nutr. Rev. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    Dose and time of administration of GM-modifying drugs may vary depending on stage of disease, possibly further influencing study outcomes.

    “Additionally, the dose and time of administration of GM-modifying drugs may also vary depending on the stage of the disease, thus possibly further influencing the study outcomes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    GM is emerging as a promising diagnostic and therapeutic tool for PD and deserves further investigation.

    “Overall, although much work remains to be done and large clinical trials are required, GM is emerging as a promising diagnostic and therapeutic tool for PD and deserves further investigation.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Findings from animal models of FMT in PD can be extrapolated to human PD patients.
    • Rests on an assumption: The optimal probiotic-prebiotic cocktail and best dietary intervention for PD have not yet been identified.
89 of 89

  • The paper relies on this without support.

    Findings from animal models of Parkinson’s disease (such as MPTP, 6-OHDA, rotenone, and α-synuclein overexpression models) can be extrapolated to human Parkinson’s disease pathophysiology and treatment.

    “Treating mice where PD has been induced by MPTP with a cocktail of broad-spectrum antibiotics (ampicillin, metronidazole, and neomycin sulfate) was found to preserve TH and dopamine transporter immunoreactivities, which are generally lost upon MPTP administration [216]”

  • The paper relies on this without support.

    Associations between gut microbiota composition and Parkinson’s disease symptoms reflect causal relationships rather than reverse causation or confounding.

    “Concerning PD, dysbiosis followed by GI symptoms and gut discomfort far precedes the onset of motor dysfunctions and it is linked to neuroinflammation, as well as to alterations in dopamine, serotonin, and kynurenine metabolism through the gut-brain axis [40,41,42,43,44,45,46]”

  • The paper relies on this without support.

    Diet is probably the most influential factor in determining the structure and metabolic function of the intestinal microbiota.

    “As a matter of fact, diet is probably the most influential factor in determining the structure and metabolic function of the intestinal microbiota.”

  • The paper relies on this without support.

    Findings from animal models of FMT in PD can be extrapolated to human PD patients.

    “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).”
    “In line with preclinical data, PD patients undergoing FMT showed an increased presence of Blautia and Prevotella and a diminished overall abundance of Bacteroidetes, thus confirming the efficacy of this approach in modifying the GM composition [475].”

  • The paper relies on this without support.

    The optimal probiotic-prebiotic cocktail and best dietary intervention for PD have not yet been identified.

    “Furthermore, the optimal probiotic-prebiotic cocktail to be employed has yet to be identified, as well as the best dietary intervention.”
5 of 5

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?

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.

  • Cell-culture result is described as occurring in brain regions

    Minor

    The sentence attributes reduced neuronal loss in the substantia nigra and striatum to an SH-SY5Y cell model. Those brain regions are not present in the cell model as described.

1 of 1

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Authors
Varesi, A., Campagnoli, L. I. M., Fahmideh, F., Pierella, E., Romeo, M., Ricevuti, G., Nicoletta, M., Chirumbolo, S., & Pascale, A.
Affiliations
  • University of Pavia (IT)
  • University of Lancashire (GB)
  • Department of Drug Sciences, Section of Pharmacology, University of Pavia, 27100 Pavia, Italy
  • University of Verona (IT)
Corresponding author
Pascale, Alessia
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2022-10-14
Volume
23
Issue
20
Pages
12289
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms232012289
PMC
PMC9603886
OpenAlex
W4306385384
Cited by
88
References
518
Citations by year
2026: 20 · 2025: 29 · 2024: 23 · 2023: 16
FWCI
2.45
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • CLOK (University of Central Lancashire) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
Parkinson's disease, gut microbiota, gut-brain axis, dysbiosis, intestinal permeability, leaky gut, disease biomarkers, probiotics, prebiotics, antibiotics, dietary intervention, fecal microbiota transplantation, Parkinson's disease medications, nasal microbiota, oral microbiota, neurodegenerative diseases
MeSH terms
Gastrointestinal Microbiome, Anti-Bacterial Agents, Humans, Parkinson Disease, Biomarkers, Dysbiosis

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 2026-10-07.

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