scholarly journals Altered Gut Microbiota Related to Inflammatory Responses in Patients With Huntington’s Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Gang Du ◽  
Wei Dong ◽  
Qing Yang ◽  
Xueying Yu ◽  
Jinghong Ma ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Clinical Characteristics ◽  
Inflammatory Responses ◽  
Plasma Concentrations ◽  
Fecal Microbiota ◽  
Healthy Controls ◽  
Fecal Microbiome ◽  
Cytokine Responses ◽  
Α Diversity

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-γ), interleukin 1 beta (IL-1β), 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 α-diversity (richness), β-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.

scholarly journals Cognitive and Motor Norms for Huntington’s Disease

2020 ◽  
Vol 35 (6) ◽  
pp. 671-682
Author(s):  
James A Mills ◽  
Jeffrey D Long ◽  
Amrita Mohan ◽  
Jennifer J Ware ◽  
Cristina Sampaio
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Rating Scale ◽  
Word Reading ◽  
Natural Aging ◽  
Color Naming ◽  
Stroop Interference ◽  
Healthy Controls ◽  
Aging Effects ◽  
Motor Score

Abstract Background The progression of Huntington’s disease (HD) for gene-expanded carriers is well-studied. Natural aging effects, however, are not often considered in the evaluation of HD progression. Objective To examine the effects of natural aging for healthy controls and to develop normative curves by age, sex, and education from the distribution of observed scores for the Symbol Digit Modalities Test, Stroop Word Reading Test, Stroop Color Naming Test, Stroop Interference Test, Total Motor Score, and Total Functional Capacity (TFC) from the Unified Huntington’s Disease Rating Scale (UHDRS) along with a composite score. Methods After combining longitudinal REGISTRY and Enroll-HD data, we used quantile regression and natural cubic splines for age to fit models for healthy controls (N = 3,394; N observations = 8,619). Normative curves were estimated for the 0.05, 0.25, 0.50, 0.75, and 0.95 quantiles. Two types of reference curves were considered: unconditional curves were dependent on age alone, whereas conditional curves were dependent on age and other covariates, namely sex and education. Results Conditioning on education was necessary for the Symbol Digit, Stroop Word, Stroop Color, Stroop Interference, and composite UHDRS. Unconditional curves were sufficient for the Total Motor Score. TFC was unique in that the curve was constant over age with its intercept at the maximum score (TFC = 13). For all measures, sex effects were minimal, so conditioning on sex was unwarranted. Conclusions Extreme quantile estimates for each measure can be considered as boundaries for natural aging and scores falling beyond these thresholds are likely the result of disease progression. Normative curves and tables are developed and can serve as references for clinical characterization in HD.

scholarly journals Internal consistency of a Brazilian version of the unified Huntington's disease rating scale

2004 ◽  
Vol 62 (4) ◽  
pp. 977-982 ◽  
Author(s):  
Vitor Tumas ◽  
Sarah Teixeira Camargos ◽  
Paulo Samandar Jalali ◽  
Adriano de Paula Galesso ◽  
Wilson Marques Jr
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Internal Consistency ◽  
Negative Correlation ◽  
Clinical Characteristics ◽  
Rating Scale ◽  
Functional Evaluation ◽  
Brazilian Version ◽  
Disease Rating ◽  
High Degree

We evaluated the reliability of a translated Brazilian version of the Unified Huntington's Disease Rating Scale (UHDRS) to establish the reproducibility of the scale in a population that differs substantially from that on which the scale was originally validated. After a training period with the video and guidelines requested from the Huntington Study Group, we applied the UHDRS, except for the cognitive tests, to a group of 21 Brazilian patients with a molecular diagnosis of Huntington's disease (HD). We found a high degree of internal consistency of the motor section of the UHDRS (Cronbach's alpha= 0.841). There was a negative correlation between the total motor score and the functional assessment, the independence scale and the functional capacity. There was a positive correlation between these 3 scales of functional evaluation and a negative correlation between the age of onset of the disease and the number of CAG repeats. The behavioral scale and disease duration were not correlated with any factor. The clinical characteristics of this sample of patients as described by the UHDRS were roughly similar to those reported in the original validation studies and the correlations described were similar to those reported previously. We conclude that the Brazilian version of the UHDRS is reliable and valid to study patients with HD in the Brazilian setting, that this sample of Brazilian patients had clinical characteristics similar to those observed in other world regions, as expected, and that the clinical training method used for the application of the UHDRS was effective to insure a high degree of clinical reproducibility.

Reduced autonomic responsiveness to gambling task losses in Huntington's disease

2004 ◽  
Vol 10 (2) ◽  
pp. 239-245 ◽  
Author(s):  
MEGHAN C. CAMPBELL ◽  
JULIE C. STOUT ◽  
PETER R. FINN
Keyword(s):  
Decision Making ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Decision Task ◽  
Healthy Controls ◽  
Gambling Task ◽  
Risky Decision ◽  
Skin Conductance Responses ◽  
Decision Making Processes

We examined the possible role of autonomic activity in Huntington's disease (HD) during a risky decision making task. Skin conductance responses (SCRs) of 15 HD participants and 16 healthy controls were measured while they performed a computerized version of the Simulated Gambling Task (SGT). The results replicated our previous finding of a performance decrement in HD, and showed that HD was associated with an altered pattern of SCRs during the risky decision task. Specifically, the healthy controls produced increased SCRs following selections from the disadvantageous decks and following losing selections. In contrast, the SCRs of the HD group did not differentiate between wins and losses. These findings indicate a reduced impact of loss on decision-making processes under risky conditions in HD. (JINS, 2004, 10, 239–245.)

Assessing Impairment of Executive Function and Psychomotor Speed in Premanifest and Manifest Huntington’s Disease Gene-expansion Carriers

2015 ◽  
Vol 21 (3) ◽  
pp. 193-202 ◽  
Author(s):  
Ida Unmack Larsen ◽  
Tua Vinther-Jensen ◽  
Anders Gade ◽  
Jørgen Erik Nielsen ◽  
Asmus Vogel
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neuropsychological Testing ◽  
Distinct Group ◽  
Healthy Controls ◽  
Psychomotor Speed ◽  
Gene Expansion ◽  
Individual Scores ◽  
Hd Gene ◽  
Group Comparisons

AbstractExecutive functions (EF) and psychomotor speed (PMS) has been widely studied in Huntington’s disease (HD). Most studies have focused on finding markers of disease progression by comparing group means at different disease stages. Our aim was to investigate performances on nine measures of EF and PMS in a group of premanifest and manifest HD-gene expansion carriers and to investigate which measures were most sensitive for assessment of individual patients by analyzing frequencies of impaired performances relative to healthy controls. We recruited HD gene-expansion carriers, 48 manifest and 50 premanifest and as controls 39 healthy gene-expansion negative individuals. All participants underwent neurological examination and neuropsychological testing with nine cognitive measures. The frequency of impairment was investigated using cutoff scores. In group comparisons the manifest HD gene-expansion carriers scored significantly worse than controls on all tests and in classification of individual scores the majority of scores were classified as probably impaired (10th percentile) or impaired (5th percentile) with Symbol Digit Modalities Test (SDMT) being the most frequently impaired. Group comparisons of premanifest HD gene-expansion carriers and healthy controls showed significant differences on SDMT and Alternating fluency tests. Nevertheless the frequencies of probably impaired and impaired scores on individual tests were markedly higher for Alternating and Lexical fluency tests than for SDMT. We found distinct group differences in frequency of impairment on measures of EF and PMS in manifest and premanifest HD gene-expansion carriers. Our results indicate to what degree these measures can be expected to be clinically impaired. (JINS, 2015, 21, 1–10)

scholarly journals Alterations of Serum Metabolites and Fecal Microbiota Involved in Ewe Follicular Cyst

2021 ◽  
Vol 12 ◽  
Author(s):  
Tao Feng ◽  
Hongxiang Ding ◽  
Jing Wang ◽  
Wei Xu ◽  
Yan Liu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Polycystic Ovary ◽  
Bacterial Community Composition ◽  
Fecal Microbiota ◽  
Serum Metabolites ◽  
Fecal Microbiome ◽  
Follicular Cyst ◽  
Α Diversity ◽  
Potential Strategy ◽  
Follicular Cysts

While the interactions of the gut microbiome and blood metabolome have been widely studied in polycystic ovary disease in women, follicular cysts of ewes have been scarcely investigated using these methods. In this study, the fecal microbiome and serum metabolome were used to compare between ewes diagnosed with ovarian cystic follicles and ewes with normal follicles, to investigate alterations of the fecal bacterial community composition and metabolic parameters in relation to follicular cystogenesis. Ewes from the same feeding and management system were diagnosed with a follicular cyst (n = 6) or confirmed to have normal follicles (n = 6) by using a B-mode ultrasound scanner. Blood serum and fresh fecal samples of all ewes were collected and analyzed. The α-diversity of fecal microbiome did not differ significantly between follicular cyst ewes and normal follicle ewes. Three genera (Bacteroides, Anaerosporobacter, and Angelakisella) were identified and their balance differentiated between follicular cyst and normal follicle ewes. Alterations of several serum metabolite concentrations, belonging to lipids and lipid-like molecules, organic acids and derivatives, organic oxygen compounds, benzenoids, phenylpropanoids and polyketides, and organoheterocyclic compounds, were associated with the presence of a follicular cyst. Correlation analysis between fecal bacterial communities and serum metabolites indicated a positive correlation between Anaerosporobacter and several fatty acids, and a negative correlation between Bacteroides and L-proline. These observations provide new insights for the complex interactions of the gut microbiota and the host serum lipid profiles, and support gut microbiota as a potential strategy to treat and prevent follicular cysts in sheep.

scholarly journals Evaluation of gait initiation parameters using inertial sensors in Huntington's Disease: Insights into anticipatory postural adjustments and cognitive interference

2020 ◽  
Author(s):  
Radhika Desai ◽  
Nora E Fritz ◽  
Lisa Muratori ◽  
Jeffrey M. Hausdorff ◽  
Lori Quinn
Keyword(s):  
Cognitive Load ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Gait Speed ◽  
Load Condition ◽  
Anticipatory Postural Adjustments ◽  
Gait Initiation ◽  
Healthy Controls ◽  
Postural Adjustments ◽  
Single Task

Background and Purpose: Understanding the contribution of anticipatory postural adjustments (APA) on walking ability in individuals with Huntington's disease (HD) may provide insight into motor planning and the functional consequences of HD-specific cortical-basal ganglia pathway dysfunctions. The purpose of this study was to evaluate inertial measurement unit (IMU)-derived measures of APAs and first step parameters, and their contribution to gait speed, in individuals with and without manifest HD during a single-task and cognitive load condition. Methods: 33 individuals with manifest HD and 15 age-matched healthy controls wore three Opal APDM IMUs during a 14-meter walk during a single task and cognitive load condition. APA acceleration amplitudes, APA durations, first step range of motion (ROMs), and first step duration were compared, along with their relationship to gait speed. Results: Individuals with HD had significantly greater APA acceleration amplitudes, smaller first step ROMs and longer first step durations compared to healthy controls. No difference in APA durations were present between groups across conditions. Linear model results and significant correlations between mediolateral APA acceleration amplitudes and APA durations were found. Conclusions: Larger acceleration amplitudes, smaller first step ROMs of greater duration, accompanied by the preservation of APA durations reveal a discrepancy in movement scaling in HD. Additionally, the mediolateral component of the APA is likely a rate-limiting factor that drives a compensatory response in gait initiation. Additional research is needed to explore the neural correlates of HD-related movement scaling.

scholarly journals Levels of Interleukin-6 in Saliva, but Not Plasma, Correlate with Clinical Metrics in Huntington’s Disease Patients and Healthy Control Subjects

2020 ◽  
Vol 21 (17) ◽  
pp. 6363 ◽  
Author(s):  
Jody Corey-Bloom ◽  
Ryan S. Fischer ◽  
Aeri Kim ◽  
Chase Snell ◽  
Georgia M. Parkin ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Interleukin 6 ◽  
Inflammatory Responses ◽  
Neurodegenerative Disorder ◽  
Interleukin 1 ◽  
Peripheral Tissues ◽  
Reactive Protein ◽  
Control Subjects ◽  
Healthy Control

Growing evidence suggests that inflammatory responses, in both the brain and peripheral tissues, contribute to disease pathology in Huntington’s disease (HD), an inherited, progressive neurodegenerative disorder typically affecting adults in their 30–40 s. Hence, studies of inflammation-related markers in peripheral fluids might be useful to better characterize disease features. In this study, we measured levels of C-reactive protein (CRP), Interleukin-6 (IL-6), interleukin 1 beta (IL-1B), and alpha-amylase (AA) in saliva and plasma from n = 125 subjects, including n = 37 manifest HD patients, n = 36 premanifest patients, and n = 52 healthy controls, using immunoassays. We found increases in salivary levels of IL-6, IL-1B and CRP across different disease groups and increased levels of IL-6 in the plasma of HD patients as compared to premanifest patients and controls. The levels of salivary IL-6 were significantly correlated with each of the other salivary markers, as well as with IL-6 levels measured in plasma. Further, salivary IL-6 and IL-1B levels were significantly positively correlated with Total Motor Score (TMS) and chorea scores and negatively correlated with Total Functional Capacity (TFC) in HD patients, whereby in healthy control subjects, IL-6 was significantly negatively correlated with Montreal Cognitive Assessment (MoCA) and the Symbol Digit Modalities test (SDM). Interestingly, the plasma levels of IL-6 did not show similar correlations to any clinical measures in either HD or control subjects. These findings suggest that salivary IL-6 is particularly relevant as a potential non-invasive biomarker for HD symptoms. The advent of an effective, dependable salivary biomarker would meet the urgent need for a less invasive means of identifying and monitoring HD disease progression.

Fecal microbiota in untreated children with Juvenile Idiopathic Arthritis – a comparison with healthy children and healthy siblings

2020 ◽  
pp. jrheum.200551
Author(s):  
Anders Öman ◽  
Johan Dicksved ◽  
Lars Engstrand ◽  
Lillemor Berntson
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Community Composition ◽  
Alpha Diversity ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Healthy Children ◽  
Healthy Controls ◽  
Α Diversity ◽  
Healthy Siblings ◽  
Relative Abundances

Objective Changes in the composition of gut microbiota has been suggested to be associated with Juvenile idiopathic arthritis (JIA). The objective in this study was to investigate if the diversity and composition of the fecal microbiota differed between children with JIA and healthy controls, and if the microbiota differed between children with JIA and their healthy siblings. Methods In this multicenter, case-control study, fecal samples were collected from 75 children with JIA and 32 healthy controls. Eight of the healthy controls were siblings to eight children with JIA and they were compared only pairwise with their siblings. The microbiota was determined using sequencing amplicons from the V3 and V4 regions of the 16S rRNA gene. Alpha diversity, community composition of microbiota and relative abundances of taxa were compared between children with JIA and healthy unrelated controls as well as between children with JIA and healthy siblings. Results Our data revealed no significant differences in α-diversity or community composition of microbiota between children with JIA, healthy unrelated controls or healthy siblings. Analyses of relative abundances of phyla, families and genera identified trends of differing abundances of some taxa in children with JIA, in comparison with both healthy controls and healthy siblings, but none of these findings were significant after adjustment for multiple comparisons. Conclusion There were no significant differences in the composition of fecal microbiota in children with JIA compared with healthy controls. The composition of microbiota in children with JIA did not differ significantly from that in their healthy siblings.

scholarly journals The effect of legume supplementation on the gut microbiota in rural Malawian infants aged 6 to 12 months

2020 ◽  
Vol 111 (4) ◽  
pp. 884-892
Author(s):  
M Isabel Ordiz ◽  
Stefan Janssen ◽  
Greg Humphrey ◽  
Gail Ackermann ◽  
Kevin Stephenson ◽  
...  
Keyword(s):  
Common Bean ◽  
Intestinal Permeability ◽  
Relative Abundance ◽  
Linear Growth ◽  
Fecal Microbiota ◽  
Sub Saharan Africa ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Fecal Microbiome ◽  
Α Diversity

ABSTRACT Background Common bean and cowpea contain about 25% protein and 25% fiber, and are recommended as complementary foods in sub-Saharan Africa. Objective The objective of this study was to determine if a daily legume supplement given to Malawian infants aged 6 to 12 mo alters the 16S configuration of the fecal microbiota as read out by amplicon sequence variants (ASVs). Methods This study was conducted within the context of a randomized, double-blind, controlled clinical trial to assess whether cowpea or common bean supplementation reduced intestinal permeability or increased linear growth. There were 2 village clusters in which the study was conducted. Fresh stool collections were flash frozen from 236 infants at ≤6 time points. The stools were sequenced using Earth Microbiome project protocols and data were processed using Qiime and Qiita, open-source, validated software packages. α-diversity was measured using the Faith's test. The 16S configuration was characterized by determining the weighted UniFrac distances of the ASVs and comparing them using permutational multivariate ANOVA. Results Among the 1249 samples analyzed, the α-diversity of the fecal microbiome was unchanged among subjects after initiation of legume supplementation. Neither cowpea nor common bean altered the overall 16S configuration at any age. The 16S configuration differed between children with adequate and poor linear growth aged from 6 to 9 mo, but no specific ASVs differed in relative abundance. The 16S configuration differed between children with normal and abnormal intestinal permeability at 9 mo, but no specific ASVs differed in relative abundance. Among categorical characteristics of the population associated with different 16S configurations, village cluster was most pronounced. Conclusion Legume supplementation in breastfed, rural African infants did not affect the structure of the gut microbial communities until the children were aged 9 mo. This trial was registered at clinicaltrials.gov as NCT02472262.

Sign in / Sign up

Export Citation Format

Share Document