Inflammatory microbes and genes as potential biomarkers of Parkinson’s disease

Abstract

As the second-largest neurodegenerative disease in the world, Parkinson’s disease (PD) has brought a severe economic and medical burden to our society. Growing evidence in recent years suggests that the gut microbiome may influence PD, but the exact pathogenesis of PD remains unclear. In addition, the current diagnosis of PD could be inaccurate and expensive. In this study, the largest meta-analysis currently of the gut microbiome in PD was analyzed, including 2269 samples by 16S rRNA gene and 236 samples by shotgun metagenomics, aiming to reveal the connection between PD and gut microbiome and establish a model to predict PD. The results showed that the relative abundances of potential pro-inflammatory bacteria, genes and pathways were significantly increased in PD, while potential anti-inflammatory bacteria, genes and pathways were significantly decreased. These changes may lead to a decrease in potential anti-inflammatory substances (short-chain fatty acids) and an increase in potential pro-inflammatory substances (lipopolysaccharides, hydrogen sulfide and glutamate). Notably, the results of 16S rRNA gene and shotgun metagenomic analysis have consistently identified five decreased genera (Roseburia, Faecalibacterium, Blautia, Lachnospira, and Prevotella) and five increased genera (Streptococcus, Bifidobacterium, Lactobacillus, Akkermansia, and Desulfovibrio) in PD. Furthermore, random forest models performed well for PD prediction based on 11 genera (accuracy > 80%) or 6 genes (accuracy > 90%) related to inflammation. Finally, a possible mechanism was presented to explain the pathogenesis of inflammation leading to PD. Our results provided further insights into the prediction and treatment of PD based on inflammation.

Parkinson’s Disease: A Tale of Many Players

“…Additionally, the concentration of these bacterial species correlated with the clinically observed severity of PD ( p < 0.01). Very recent Chinese research has confirmed these results [[88]], which suggests that Desulfovibrio bacteria take part in the pathogenesis of PD, which opens a new avenue for patient classification and treatment.…”

Lactobacillus plantarum CCFM405 against Rotenone-Induced Parkinson’s Disease Mice via Regulating Gut Microbiota and Branched-Chain Amino Acids Biosynthesis

“…Many studies have shown that individuals with PD have a much higher prevalence of Akkermansia and Akkermansia muciniphila than healthy participants, suggesting that Akkermansia may be associated with the pro-inflammatory state of PD [ 16 ]. Interestingly, in our study, rotenone intake markedly increased the abundance of Akkermansia , which is consistent with the results of patients with PD.…”

“…Hence, the microbiota in the gut may affect the concentrations of plasma amino acids. Emerging evidence indicates that individuals with PD suffer from unbalanced gut microbiota compositions [ 16 , 76 ], which suggests that gut microbes are implicated in the pathophysiology of PD. The brain requires BCAAs as a nitrogen source to keep the glutamate–glutamine cycle between astrocytes and neurons functioning correctly [ 77 ].…”

“…Notably, the relative abundance of potentially pro-inflammatory bacteria, genes, and pathways in PD patients was significantly increased, while potentially anti-inflammatory bacteria, genes, and pathways were significantly decreased. This may result in a decrease in potentially anti-inflammatory substances (short-chain fatty acids, SCFAs) and an increase in potentially pro-inflammatory substances (lipopolysaccharides, hydrogen sulfide, and glutamate) [ 16 ].…”

Supplementation with short-chain fatty acids and the prebiotic 2FL improves clinical outcome in PD

“…3 Growing evidence supports the idea that microbial dysbiosis, leaky gut syndrome and a proinflammatory intestinal environment are central components of the pathogenesis of PD. [4][5][6][7] The gut metabolome is essential for metabolic homeostasis but is also involved in communication between the microbiome and the subepithelial structures of the gut, which has multifold systemic implications for the organism. Short-chain fatty acids (SCFAs) are a major group of metabolites involved in the microbiome-gut interaction and are produced through the anaerobic fermentation of dietary fibers.…”