Functional implications of microbial and viral gut metagenome changes in early stage L-DOPA-naïve Parkinson’s disease patients

Abstract

BackgroundParkinson’s disease (PD) presently is conceptualized as a protein aggregation disease in which pathology involves both the enteric and the central nervous system, possibly spreading from one to another via the vagus nerves. As gastrointestinal dysfunction often precedes or parallels motor symptoms, the enteric system with its vast diversity of microorganisms may be involved in PD pathogenesis. Alterations in the enteric microbial taxonomic level of L-DOPA-naïve PD patients might also serve as a biomarker.MethodsWe performed metagenomic shotgun analyses and compared the fecal microbiomes of 31 early stage, L-DOPA-naïve PD patients to 28 age-matched controls.ResultsWe found increased Verrucomicrobiaceae (Akkermansia muciniphila) and unclassified Firmicutes, whereas Prevotellaceae (Prevotella copri) and Erysipelotrichaceae (Eubacterium biforme) were markedly lowered in PD samples. The observed differences could reliably separate PD from control with a ROC-AUC of 0.84. Functional analyses of the metagenomes revealed differences in microbiota metabolism in PD involving the ẞ-glucuronate and tryptophan metabolism. While the abundances of prophages and plasmids did not differ between PD and controls, total virus abundance was decreased in PD participants. Based on our analyses, the intake of either a MAO inhibitor, amantadine, or a dopamine agonist (which in summary relates to 90% of PD patients) had no overall influence on taxa abundance or microbial functions.ConclusionsOur data revealed differences of colonic microbiota and of microbiota metabolism between PD patients and controls at an unprecedented detail not achievable through 16S sequencing. The findings point to a yet unappreciated aspect of PD, possibly involving the intestinal barrier function and immune function in PD patients. The influence of the parkinsonian medication should be further investigated in the future in larger cohorts.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-017-0428-y) contains supplementary material, which is available to authorized users.

Gut Vibes in Parkinson's Disease: The Microbiota‐Gut‐Brain Axis

“…At the family level, Scheperjans and colleagues found a significant reduction of 78% in the abundance of Prevotellaceae in feces of PD patients compared to healthy controls, confirmed by the also significant decrease observed in the Heintz‐Buschart and colleagues and reinforced by the strong downward trend reported in three other studies here reviewed, which failed to reach statistical significant differences . In contrast to Prevotellaceae, Verrucomicrobiaceae was found to be enriched in four studies . Other reproducible findings were increased abundance of Lactobacillaceae, only refuted by the Unger and colleagues study, and reduced abundance of Lachnospiraceae …”

“…Multiple studies also revealed an increase in Bifidobacterium and Lactobacillus , aligning with the increase in the abundance of these bacteria in the colon and small intestine of rotenone‐treated rats and in stool samples of rotenone‐treated mice . On the other hand, the abundances of genera such as Faecalibacterium (including the species Faecalibacterium prausnitzii ), Blautia (including the species Blautia glucerase ), and Prevotella (including Prevotella levels with a remarkable but nonsignificant reduction) were significantly impoverished in fecal samples of PD patients. In addition, Keshavarzian and colleagues observed a nonsignificant decrease in Prevotella in mucosal biopsies of PD patients .…”

“…For instance, Clostridiaceae, as well as several clusters and genera from this family, were increased . However, specific Clostridium species were reduced . Moreover, Bacteroides showed lower abundance at the genus and species levels, except in the Keshavarzian and colleagues study .…”

“…At the family level, Scheperjans and colleagues and Hopfner and colleagues found four and three different taxa, respectively, predicting PD . At the genus level, Bedarf and colleagues and Qian and colleagues found 5 and 18 different taxa, respectively, predicting PD . The areas under curve were similar among the four studies and indicated that the taxa included may be a valuable tool to identify PD patients before motor symptoms development.…”

“…To date, 13 studies have described gut bacterial changes in fecal samples of PD patients, including one longitudinal study (Supporting Information Tables S1 and S2).…”