Systematic analysis of gut microbiome reveals the role of bacterial folate and homocysteine metabolism in Parkinson’s disease

Rosário, Dorinês; Bidkhori, Gholamreza; Lee, Sunjae; Bedarf, Janis R.; Hildebrand, Falk; Uhlén, Mathias; Ehrlich, S. Dusko; Proctor, Gordon; Wüllner, Ullrich; Mardinoğlu, Adil; Shoaie, Saeed

doi:10.1016/j.celrep.2021.108807

Cited by 99 publications

(87 citation statements)

References 71 publications

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“…Decreased long-chain acylcarnitines due to insufficient β-oxidation has been shown to carry potential for early diagnosis of Parkinson’s 28 , especially 12–14 long chain acylcarnitines. In recent work studying the gut microbiome, Rosario et al 29 have shown the role of bacterial folate and homocysteine metabolism in PD. Higher numbers of bacterial mucin and host degradation enzymes were linked to the manifestation of PD.…”

Section: Discussionmentioning

confidence: 99%

Multiomics implicate gut microbiota in altered lipid and energy metabolism in Parkinson’s disease

Pereira

Trivedi

Silverman

et al. 2022

npj Parkinsons Dis.

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We aimed to investigate the link between serum metabolites, gut bacterial community composition, and clinical variables in Parkinson’s disease (PD) and healthy control subjects (HC). A total of 124 subjects were part of the study (63 PD patients and 61 HC subjects). 139 metabolite features were found to be predictive between the PD and Control groups. No associations were found between metabolite features and within-PD clinical variables. The results suggest alterations in serum metabolite profiles in PD, and the results of correlation analysis between metabolite features and microbiota suggest that several bacterial taxa are associated with altered lipid and energy metabolism in PD.

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Section: Discussionmentioning

confidence: 99%

Multiomics implicate gut microbiota in altered lipid and energy metabolism in Parkinson’s disease

Pereira

Trivedi

Silverman

et al. 2022

npj Parkinsons Dis.

View full text Add to dashboard Cite

show abstract

“…In recent work studying the gut microbiome, Rosario et al . (2021) 22 have shown the role of bacterial folate and homocysteine metabolism in PD. Higher numbers of bacterial mucin and host degradation enzymes were linked to the manifestation of PD.…”

Section: Discussionmentioning

confidence: 99%

“…Decreased long-chain acylcarnitines due to insufficient β-oxidation has been shown to carry potential for early diagnosis of Parkinson's 21 , especially 12-14 long chain acylcarnitines. In recent work studying the gut microbiome, Rosario et al (2021) 22 have shown the role of bacterial folate and homocysteine metabolism in PD. Higher numbers of bacterial mucin and host degradation enzymes were linked to the manifestation of PD.…”

Section: Serum Metabolomementioning

confidence: 99%

Multiomics implicate gut microbiota in altered lipid and energy metabolism in Parkinson’s disease

Pereira

Silverman

et al. 2021

Preprint

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We aimed to investigate the link between serum metabolites, gut bacterial community composition, and clinical variables in Parkinsons disease (PD) and healthy control subjects (HC). 139 metabolite features were found to be differentially abundant between the PD and Control groups. No associations were found between metabolite features and within-PD clinical variables. The results suggest alterations in serum metabolite profiles in PD, and the results of correlation analysis between metabolite features and microbiota suggest that several bacterial taxa are associated with altered lipid and energy metabolism in PD.

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“…Although still controversial, several lines of evidence from metagenomic studies of PD patients and healthy age-matched individuals suggest dysbiosis within the gut microbiome of PD patients could modify the risk and progressively worsen disease status (Sampson et al, 2016;Qian et al, 2020;Romano et al, 2021). Despite methodological differences across studies, including inclusion criterion, sample collection, disease status, or additional confounders, contributing to divergent microbial profiles, the evidence of microbial dysbiosis in PD is consistent (Romano et al, 2021;Rosario et al, 2021). Individuals with PD have dramatically divergent microbial profiles compared to healthy controls (Romano et al, 2021).…”

Section: Gut Microbiome and Neurodegenerative Diseases Parkinson's Di...mentioning

confidence: 99%

“…As dietary fiber is vital for maintaining the colonic mucus barrier, fiber deficiency favors the proliferation of distinct microbial populations that degrade the colonic mucus layer and enable enhanced colonization and infiltration of opportunistic pathogens (Desai et al, 2016). Akkermansia spp., relatively sparse in healthy subjects, are consistently enriched in PD samples versus controls (Hill-Burns et al, 2017;Wallen et al, 2020;Rosario et al, 2021) and are increasingly abundant in the fecal microbiome of patients who experience constipation, a primary non-motor symptom of PD. Nishiwaki et al (2020) implicated this genus in the neuropathological progression of PD by mechanisms of degrading mucin.…”

Section: Gut Microbiome and Neurodegenerative Diseases Parkinson's Di...mentioning

confidence: 99%

Mechanistic Insights Into Gut Microbiome Dysbiosis-Mediated Neuroimmune Dysregulation and Protein Misfolding and Clearance in the Pathogenesis of Chronic Neurodegenerative Disorders

et al. 2022

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The human gut microbiota is a complex, dynamic, and highly diverse community of microorganisms. Beginning as early as in utero fetal development and continuing through birth to late-stage adulthood, the crosstalk between the gut microbiome and brain is essential for modulating various metabolic, neurodevelopmental, and immune-related pathways. Conversely, microbial dysbiosis – defined as alterations in richness and relative abundances – of the gut is implicated in the pathogenesis of several chronic neurological and neurodegenerative disorders. Evidence from large-population cohort studies suggests that individuals with neurodegenerative conditions have an altered gut microbial composition as well as microbial and serum metabolomic profiles distinct from those in the healthy population. Dysbiosis is also linked to psychiatric and gastrointestinal complications – comorbidities often associated with the prodromal phase of Parkinson’s disease (PD) and Alzheimer’s disease (AD). Studies have identified potential mediators that link gut dysbiosis and neurological disorders. Recent findings have also elucidated the potential mechanisms of disease pathology in the enteric nervous system prior to the onset of neurodegeneration. This review highlights the functional pathways and mechanisms, particularly gut microbe-induced chronic inflammation, protein misfolding, propagation of disease-specific pathology, defective protein clearance, and autoimmune dysregulation, linking gut microbial dysbiosis and neurodegeneration. In addition, we also discuss how pathogenic transformation of microbial composition leads to increased endotoxin production and fewer beneficial metabolites, both of which could trigger immune cell activation and enteric neuronal dysfunction. These can further disrupt intestinal barrier permeability, aggravate the systemic pro-inflammatory state, impair blood–brain barrier permeability and recruit immune mediators leading to neuroinflammation and neurodegeneration. Continued biomedical advances in understanding the microbiota-gut-brain axis will extend the frontier of neurodegenerative disorders and enable the utilization of novel diagnostic and therapeutic strategies to mitigate the pathological burden of these diseases.

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Systematic analysis of gut microbiome reveals the role of bacterial folate and homocysteine metabolism in Parkinson’s disease

Cited by 99 publications

References 71 publications

Multiomics implicate gut microbiota in altered lipid and energy metabolism in Parkinson’s disease

Multiomics implicate gut microbiota in altered lipid and energy metabolism in Parkinson’s disease

Multiomics implicate gut microbiota in altered lipid and energy metabolism in Parkinson’s disease

Mechanistic Insights Into Gut Microbiome Dysbiosis-Mediated Neuroimmune Dysregulation and Protein Misfolding and Clearance in the Pathogenesis of Chronic Neurodegenerative Disorders

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