Dataset Information

Altered Gut Microbiota Related to Inflammatory Responses in Patients With Huntington's Disease.

ABSTRACT: Emerging evidence indicates that gut dysbiosis may play a regulatory role in the onset and progression of Huntington's disease (HD). However, any alterations in the fecal microbiome of HD patients and its relation to the host cytokine response remain unknown. The present study investigated alterations and host cytokine responses in patients with HD. We enrolled 33 HD patients and 33 sex- and age- matched healthy controls. Fecal microbiota communities were determined through 16S ribosomal DNA gene sequencing, from which we analyzed fecal microbial richness, evenness, structure, and differential abundance of individual taxa between HD patients and healthy controls. HD patients were evaluated for their clinical characteristics, and the relationships of fecal microbiota with these clinical characteristics were analyzed. Plasma concentrations of interferon gamma (IFN-?), interleukin 1 beta (IL-1?), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor alpha were measured by Meso Scale Discovery (MSD) assays, and relationships between microbiota and cytokine levels were analyzed in the HD group. HD patients showed increased ?-diversity (richness), ?-diversity (structure), and altered relative abundances of several taxa compared to those in healthy controls. HD-associated clinical characteristics correlated with the abundances of components of fecal microbiota at the genus level. Genus Intestinimonas was correlated with total functional capacity scores and IL-4 levels. Our present study also revealed that genus Bilophila were negatively correlated with proinflammatory IL-6 levels. Taken together, our present study represents the first to demonstrate alterations in fecal microbiota and inflammatory cytokine responses in HD patients. Further elucidation of interactions between microbial and host immune responses may help to better understand the pathogenesis of HD.

SUBMITTER: Du G

PROVIDER: S-EPMC7933529 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Altered Gut Microbiota Related to Inflammatory Responses in Patients With Huntington's Disease.

Du Gang G Dong Wei W Yang Qing Q Yu Xueying X Ma Jinghong J Gu Weihong W Huang Yue Y

Frontiers in immunology 20210219

Emerging evidence indicates that gut dysbiosis may play a regulatory role in the onset and progression of Huntington's disease (HD). However, any alterations in the fecal microbiome of HD patients and its relation to the host cytokine response remain unknown. The present study investigated alterations and host cytokine responses in patients with HD. We enrolled 33 HD patients and 33 sex- and age- matched healthy controls. Fecal microbiota communities were determined through 16S ribosomal DNA gen ...[more]

PMID: 33679692

Similar Datasets

Project description:ObjectiveEmerging evidence suggests that gut microbiome composition alterations affect neurodegeneration through neuroinflammation in the pathogenesis of Parkinson's disease (PD). Here, we evaluate gut microbiota alterations and host cytokine responses in a population of Taiwanese patients with PD.MethodsFecal microbiota communities from 80 patients with PD and 77 age and gender-matched controls were assessed by sequencing the V3-V4 region of the 16S ribosomal RNA gene. Diet and comorbidities were controlled in the analyses. Plasma concentrations of IL-1β, IL-2, IL-4, IL-6, IL-13, IL-18, GM-CSF, IFNγ, and TNFα were measured by a multiplex immunoassay and relationships between microbiota, clinical characteristics, and cytokine levels were analyzed in the PD group. We further examined the cytokine changes associated with the altered gut microbiota seen in patients with PD in another independent cohort of 120 PD patients and 120 controls.ResultsMicrobiota from patients with PD was altered relative to controls and dominated by Verrucomicrobia, Mucispirillum, Porphyromonas, Lactobacillus, and Parabacteroides. In contrast, Prevotella was more abundant in controls. The abundances of Bacteroides were more increased in patients with non-tremor PD subtype than patients with tremor subtype. Bacteroides abundance was correlated with motor symptom severity defined by UPDRS part III motor scores (rho = 0.637 [95% confidence interval 0.474 to 0.758], P < 0.01). Altered microbiota was correlated with plasma concentrations of IFNγ and TNFα. There was a correlation between Bacteroides and plasma level of TNFα (rho = 0.638 [95% CI: 0.102-0.887], P = 0.02); and a correlation between Verrucomicrobia abundance and plasma concentrations of IFNγ (rho = 0.545 [95% CI - 0.043-0.852], P = 0.05). The elevated plasma cytokine responses were confirmed in an additional independent 120 patients with PD and 120 controls (TNFα: PD vs. control 8.51 ± 4.63 pg/ml vs. 4.82 ± 2.23 pg/ml, P < 0.01; and IFNγ: PD vs. control: 38.45 ± 7.12 pg/ml vs. 32.79 ± 8.03 pg/ml, P = 0.03).ConclusionsThis study reveals altered gut microbiota in PD and its correlation with clinical phenotypes and severity in our population. The altered plasma cytokine profiles associated with gut microbiome composition alterations suggest aberrant immune responses may contribute to inflammatory processes in PD.

Project description:Huntington's disease is characterized by a triad of motor, cognitive and psychiatric impairments, as well as unintended weight loss. Although much of the research has focused on cognitive, motor and psychiatric symptoms, the extent of peripheral pathology and the relationship between these factors, and the core symptoms of Huntington's disease, are relatively unknown. Gut microbiota are key modulators of communication between the brain and gut, and alterations in microbiota composition (dysbiosis) can negatively affect cognition, behaviour and affective function, and may be implicated in disease progression. Furthermore, gut dysbiosis was recently reported in Huntington's disease transgenic mice. Our main objective was to characterize the gut microbiome in people with Huntington's disease and determine whether the composition of gut microbiota are significantly related to clinical indicators of disease progression. We compared 42 Huntington's disease gene expansion carriers, including 19 people who were diagnosed with Huntington's disease (Total Functional Capacity > 6) and 23 in the premanifest stage, with 36 age- and gender-matched healthy controls. Participants were characterized clinically using a battery of cognitive tests and using results from 16S V3 to V4 rRNA sequencing of faecal samples to characterize the gut microbiome. For gut microbiome measures, we found significant differences in the microbial communities (beta diversity) based on unweighted UniFrac distance (P = 0.001), as well as significantly lower alpha diversity (species richness and evenness) between our combined Huntington's disease gene expansion carrier group and healthy controls (P = 0.001). We also found major shifts in the microbial community structure at Phylum and Family levels, and identified functional pathways and enzymes affected in our Huntington's disease gene expansion carrier group. Within the Huntington's disease gene expansion carrier group, we also discovered associations among gut bacteria, cognitive performance and clinical outcomes. Overall, our findings suggest an altered gut microbiome in Huntington's disease gene expansion carriers. These results highlight the importance of gut biomarkers and raise interesting questions regarding the role of the gut in Huntington's disease, and whether it may be a potential target for future therapeutic intervention.

Dataset Information

Altered Gut Microbiota Related to Inflammatory Responses in Patients With Huntington's Disease.

Publications

Altered Gut Microbiota Related to Inflammatory Responses in Patients With Huntington's Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets