Altered Actinobacteria and Firmicutes Phylum Associated Epitopes in Patients With Parkinson’s Disease

Abstract

Recent evidence suggests that inflammation was participated in the pathogenesis of PD, thus, to understand the potential mechanism of gut microbiota in the pathogenesis of Parkinson’s disease (PD), we performed a metagenomic analysis of fecal samples from PD patient and controls. Using a two-stage metagenome-wide association strategy, fecal DNA samples from 69 PD patients and 244 controls in three groups (comprising 66 spouses, 97 age-matched, and 81 normal samples, respectively) were analyzed, and differences between candidate gut microbiota and microbiota-associated epitopes (MEs) were compared. In the study, 27 candidate bacterial biomarkers and twenty-eight candidate epitope peptides were significantly different between the PD patients and control groups. Further, enriched 4 and 13 MEs in PD were positively associated with abnormal inflammatory indicators [neutrophil percentage (NEUT.1), monocyte count/percentage (MONO/MONO.1), white blood cell count (WBC)] and five candidate bacterial biomarkers (c_Actinobacteria, f_Bifidobacteriaceae, g_Bifidobacterium, o_Bifidobacteriales, p_Actinobacteria) from Actinobacteria phylum, and they were also positively associated with histidine degradation and proline biosynthesis pathways, respectively. Additionally, enriched 2 MEs and 1 ME in PD were positively associated with above inflammatory indicators and two bacteria (f_Lactobacillaceae, g_Lactobacillus) from Firmicutes phylum, and they were also positively associated with pyruvate fermentation to propanoate I and negatively associated with isopropanol biosynthesis, respectively. Of these MEs, two MEs from GROEL2, RPSC were derived from Mycobacterium tuberculosis, triggered the T cell immune response, as previously reported. Additionally, other candidate epitope peptides derived from Mycobacterium tuberculosis and Mycobacterium leprae may also have potential immune effects in PD. In all, the altered MEs in PD may relate to abnormalities in immunity and glutamate and propionate metabolism, which furthers our understanding of the pathogenesis of PD.

T Lymphocytes in Parkinson’s Disease

“…Among these, Lactobacillaceae may induce Th1-type immune responses [ 54 ], whereas Prevotellaceae abundance was associated with augmented Th17-mediated mucosal inflammation [ 55 ]. Another study evaluating fecal DNA samples from 69 PD patients and 244 controls reported that, among the microbiota-associated epitopes involved in inflammatory pathways, two were involved in T cell responses [ 56 ]. Based on these observations, it could be speculated that T cell-related immunity, triggered by the aggregation of α -synuclein in the gut mucosa, may promote further CNS neuroinflammation and neurodegeneration.…”

The relationship between Parkinson’s disease and gastrointestinal diseases

“… Li et al (2021) found that enriched Actinobacteria and Firmicutes phylum-associated epitopes were positively associated with inflammatory indicators such as neutrophil percentage, monocyte count/percentage, and white blood cell count in PD patients. Additionally, they were also positively associated with histidine degradation and proline biosynthesis pathways ( Li et al, 2021 ). The relationship between gut microbiota, SCFAs, inflammation indicators, and the gut barrier in PD has been demonstrated.…”

“…Th1 and Th17 then enter the brain via damaged BBB and activate microglia which induces neuroinflammation (Chen et al, 2019). Li et al (2021) found that enriched Actinobacteria and Firmicutes phylum-associated epitopes were positively associated with inflammatory indicators such as neutrophil percentage, monocyte count/percentage, and white blood cell count in PD patients. Additionally, they were also positively associated with histidine degradation and proline biosynthesis pathways (Li et al, 2021).…”

Gut bacterial profiles in Parkinson's disease: A systematic review

“…In our earlier study, increased Bifidobacteriaceae and Bifidobacterium , as well as Lactobacillaceae and Lactobacillus , were found to have significant correlations with clinical inflammatory indicators including neutrophil percentage, monocyte percentage, and monocyte count. 82 On the other hand, PD medication, especially catechol‐O‐methyltransferase (COMT) inhibitors, may have an effect on them. Barichella et al 33 noticed that the use of COMT inhibitors elevated the level of Lactobacillaceae .…”