Bedarf JR, Hildebrand F, Coelho LP, Sunagawa S, Bahram M, Goeser F, Bork P, Wüllner U. Functional implications of microbial and viral gut metagenome changes in early stage L-DOPA-naïve Parkinson’s disease patients. Genome Science. April 28, 2017.

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Comments

  1. This paper has two major pluses over previous studies on the topic:
    a) It compares PD patients naïve to L-DOPA with normal controls, avoiding L-DOPA as a confounding element;
    b) It performs a metagenomic shotgun analyses, which allows high-resolution characterization of bacterial species as well as their metabolic functions.

    The major conclusion is that the microbiota of PD and controls show significant differences in species and metabolic activities. The paper is open ended as it remains to be established whether these differences are primary or secondary in the pathogenesis of the disease.

    I would like to emphasize one point that I think is rather provocative. PD patients in this study have reduced abundance of a Prevotella species. Prevotellaceae utilize fibers as substrate to produce short chain fatty acids (SCFA), suggesting that PD patients may have defective production of SCFA. This conclusion is in agreement with previous studies showing that feces from PD contain less SCFA-producing bacteria. However, this conclusion is seemingly contrast with the recent study by the Mazmanian group, who have shown that SCFA promote disease and neuroinflammation in a transgenic mouse model of PD based on overexpression of α-synuclein. Thus, the connection between intestinal microflora, metabolites and disease progression remains to be fully explored.

    View all comments by Marco Colonna

  2. The recent report by Bedarf et al. in Genome Medicine adds to the considerable evidence that the microbiota are involved in the pathogenesis of Parkinson's disease (PD) and other neurodegenerations. Their data clarify with greater detail than previously available the nature of bacterial populations in the colonic lumen in PD. The potential for the pathogenicity of intestinal microbial alterations noted by Bedard et al and others deserves consideration. Short chain fatty acids enhance the production to anti-inflammatory regulatory lymphocytes. This may be a mechanism by which neuroinflammation (which is a component of the Parkinson process in the brain) is influenced by the microbiota. Also, we have presented evidence that the production of amyloid proteins by the microbiota may be involved (see Oct 2016 news on Chen et al., 2016 and Friedland, 2015). We found that Fischer 344 rats exposed orally to the functional bacterial amyloid protein curli had enhanced cerebral inflammation and alpha synuclein aggregation, compared to animals exposed to bacteria without the ability to produce curli. The capacity for the production of amyloid proteins by bacterial populations observed by Bedardf et al. has not been explored.

    References:

    Chen SG, Stribinskis V, Rane MJ, Demuth DR, Gozal E, Roberts AM, Jagadapillai R, Liu R, Choe K, Shivakumar B, Son F, Jin S, Kerber R, Adame A, Masliah E, Friedland RP. Exposure to the Functional Bacterial Amyloid Protein Curli Enhances Alpha-Synuclein Aggregation in Aged Fischer 344 Rats and Caenorhabditis elegans. Sci Rep. 2016 Oct 6;6:34477. PubMed.

    Friedland RP. Mechanisms of molecular mimicry involving the microbiota in neurodegeneration. J Alzheimers Dis. 2015;45(2):349-62. PubMed.

    View all comments by Robert Friedland

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  1. Rumblings of Parkinson’s: Gut Microbiome Shifts in Early Stage of Disease