Mediterranean Diet Adherence in People With Parkinson's Disease Reduces Constipation Symptoms and Changes Fecal Microbiota After a 5-Week Single-Arm Pilot Study

Introduction: Non-motor symptoms of Parkinson's disease (PD) such as gastrointestinal (GI) dysfunction are common, yet little is known about how modifying dietary intake impacts PD symptoms. The aim of this study in individuals with PD was to determine whether a Mediterranean diet intervention is feasible and affects GI function, intestinal permeability and fecal microbial communities.Methods: A single-arm, 5-week Mediterranean diet intervention study was conducted in eight people with PD. Daily and weekly questionnaires were administered to determine changes in GI symptoms. Urine and stool samples were collected at baseline and after 5 weeks to assess intestinal permeability and fecal microbial communities. Additionally, live-in partners of the participants with PD were matched as controls (n = 8) for baseline urine and stool samples.Results: Participants with PD increased intake of Mediterranean diet based on adherence scores from baseline to week 5 (4.4 ± 0.6 vs. 11.9 ± 0.7; P < 0.01 with >10 representing good adherence), which was linked with weight loss (77.4 kg vs. 74.9 kg, P = 0.01). Constipation syndrome scores decreased after 5 weeks (2.3 ± 0.5 vs. 1.5 ± 0.3; P = 0.04). Bilophila, was higher at baseline in PD (0.6 ± 0.1% vs. 0.2 ± 0.1% P = 0.02) and slightly decreased after the diet intervention (0.5 ± 0.1%; P = 0.01). Interestingly, the proportion of Roseburia was significantly lower in PD compared to controls (0.6 ± 0.2% vs. 1.6 ± 0.3%; P = 0.02) and increased at week 5 (0.9 ± 0.2%; P < 0.01). No differences were observed for markers of intestinal permeability between the control and PD groups or post-intervention.Conclusions: Short-term Mediterranean diet adherence is feasible in participants with PD; correlated with weight loss, improved constipation, and modified gut microbiota.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT03851861.

The impact of Mediterranean diet on coronary plaque vulnerability, microvascular function, inflammation and microbiome after an acute coronary syndrome: study protocol for the MEDIMACS randomized, controlled, mechanistic clinical trial

Background Primary prevention trials have demonstrated that the traditional Mediterranean diet is associated with a reduction in cardiovascular mortality and morbidity. However, this benefit has not been proven for secondary prevention after an acute coronary syndrome (ACS). We hypothesized that a high-intensity Mediterranean diet intervention after an ACS decreases the vulnerability of atherosclerotic plaques by complex interactions between anti-inflammatory effects, microbiota changes and modulation of gene expression. Methods The MEDIMACS project is an academically funded, prospective, randomized, controlled and mechanistic clinical trial designed to address the effects of an active randomized intervention with the Mediterranean diet on atherosclerotic plaque vulnerability, coronary endothelial dysfunction and other mechanistic endpoints. One hundred patients with ACS are randomized 1:1 to a monitored high-intensity Mediterranean diet intervention or to a standard-of-care arm. Adherence to diet is assessed in both arms using food frequency questionnaires and biomarkers of compliance. The primary endpoint is the change (from baseline to 12 months) in the thickness of the fibrous cap of a non-significant atherosclerotic plaque in a non-culprit vessel, as assessed by repeated optical coherence tomography intracoronary imaging. Indices of coronary vascular physiology and changes in gastrointestinal microbiota, immunological status and protein and metabolite profiles will be evaluated as secondary endpoints. Discussion The results of this trial will address the key effects of dietary habits on atherosclerotic risk and will provide initial data on the complex interplay of immunological, microbiome-, proteome- and metabolome-related mechanisms by which non-pharmacological factors may impact the progression of coronary atherosclerosis after an ACS. Trial registration ClinicalTrials.govNCT03842319. Registered on 13 May 2019

Effect of exercise and diet intervention in NAFLD and NASH via GAB2 methylation

Background Nonalcoholic fatty liver disease (NAFLD) is a disorder that extends from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is effectively alleviated by lifestyle intervention. Nevertheless, DNA methylation mechanism underling the effect of environmental factors on NAFLD and NASH is still obscure. The aim of this study was to investigate the effect of exercise and diet intervention in NAFLD and NASH via DNA methylation of GAB2. Methods Methylation of genomic DNA in human NAFLD was quantified using Infinium Methylation EPIC BeadChip assay after exercise (Ex), low carbohydrate diet (LCD) and exercise plus low carbohydrate diet (ELCD) intervention. The output Idat files were processed using ChAMP package. False discovery rate on genome-wide analysis of DNA methylation (q < 0.05), and cytosine-guanine dinucleotides (CpGs) which are located in promoters were used for subsequent analysis (|Δβ|≥ 0.1). K-means clustering was used to cluster differentially methylated genes according to 3D genome information from Human embryonic stem cell. To quantify DNA methylation and mRNA expression of GRB2 associated binding protein 2 (GAB2) in NASH mice after Ex, low fat diet (LFD) and exercise plus low fat diet (ELFD), MassARRAY EpiTYPER and quantitative reverse transcription polymerase chain reaction were used. Results Both LCD and ELCD intervention on human NAFLD can induce same DNA methylation alterations at critical genes in blood, e.g., GAB2, which was also validated in liver and adipose of NASH mice after LFD and ELFD intervention. Moreover, methylation of CpG units (i.e., CpG_10.11.12) inversely correlated with mRNA expression GAB2 in adipose tissue of NASH mice after ELFD intervention. Conclusions We highlighted the susceptibility of DNA methylation in GAB2 to ELFD intervention, through which exercise and diet can protect against the progression of NAFLD and NASH on the genome level, and demonstrated that the DNA methylation variation in blood could mirror epigenetic signatures in target tissues of important biological function, i.e., liver and adipose tissue. Trialregistration International Standard Randomized Controlled Trial Number Register (ISRCTN42622771)

Properties of the Cognitive Function Battery for the MIND Diet Intervention to Prevent Alzheimer’s Disease

Objective: To evaluate the properties of the cognitive battery used in the MIND Diet Intervention to Prevent Alzheimer’s Disease. The MIND Diet Intervention is a randomized control trial to determine the relative effectiveness of the MIND diet in slowing cognitive decline and reducing brain atrophy in older adults at risk for Alzheimer’s dementia. Methods: The MIND cognitive function battery was administered at baseline to 604 participants of an average age of 70 years, who agreed to participate in the diet intervention study, and was designed to measure change over time. The battery included 12 cognitive tests, measuring the 4 cognitive domains of executive function, perceptual speed, episodic memory, and semantic memory. We conducted a principal component analysis to examine the consistency between our theoretical domains and the statistical performance of participants in each domain. To further establish the validity of each domain, we regressed the domain scores against a late-life cognitive activity score, controlling for age, race, sex, and years of education. Results: Four factors emerged in the principal component analyses that were similar to the theoretical domains. In regression equations, we found the expected associations with age, education, and late-life cognitive activity with each of the four cognitive domains. Conclusions: These results indicate that the MIND cognitive battery is a comprehensive and valid battery of four separate domains of cognitive function that can be used in diet intervention trials for older adults.

Cardiovascular, diabetes, and cancer strips: New evidences from clinical cases in Nanchang, China

Since cardiovascular, diabetes, and cancer (CDC) strips were discovered, more and more evidences support this new concept. Here, we report that clinical features and shared major risk factors (SMRF) of the CDC strips as well as the distribution of hypertension, diabetes, and cancer in Nanchang, China. It aims to provide new and solid clinical evidences by cases randomly collected and carefully screened from 2012/2013 to 2017. Typical cases with the CDC strips were presented with unhealthy “environment-sleep-emotion-exercise-diet” intervention [E(e)SEEDi] related SMRF, the distribution of hypertension, diabetes, and cancer was approximately 2:1:4, and the distribution of various cancer cases was also presented. A graphical abstract showed the association of CDC strips with SMRF. In conclusion, there are indeed the CDC strips due to new and solid clinical evidences, and the CDC strips highly link to unhealthy E(e)SEEDi related SMRF.

The gut microbial signature of gestational diabetes mellitus and the association with diet intervention

Gestational diabetes mellitus (GDM) is a high-risk pregnancy complication that is associated with metabolic disorder phenotypes, such as abnormal blood glucose and obesity. The link between microbiota and diet management contributes to metabolic homeostasis in GDM. Therefore, it is crucial to understand the structure of the gut microbiota in GDM and to explore the effect of dietary management on the microbiota structure. In this study, we analyzed the composition of the gut microbiota between 27 GDM and 30 healthy subjects at two time points using Illumina HiSeq 2500 platform. The taxonomy analyses suggested that the overall bacteria clustered by diabetes status, rather than diet intervention. Of particular interest, the phylum Acidobacteria in GDM was significantly increased, and positively correlated with blood glucose levels. Moreover, Partial least-squares discriminant analysis (PLS-DA) revealed that certain genera in the phyla Firmicutes, Bacteroidetes, Proteobacteria, and Lentisphaerae characterized the GDM gut microbiota. Correlation analysis indicated that blood glucose levels and BMI index were correlated with the relative abundance of SCFAS-producing genera. Through the comparison between the GDM and healthy samples with or without diet intervention, we discovered that the role of short-term diet management in GDM processes is associated with the change in the Firmicutes/Bacteroidetes ratio and some specific taxa, rather than an alternative gut microbial pattern. Our study have important implications for understanding the beneficial effects of diet intervention on the specific gut microbiota and thus possibly their metabolism in pregnant women with GDM.ImportanceUnderstanding the composition and dynamics of the gut microbiota in GDM women under diet intervention is important because there may be opportunities for preventive strategies. We examined the relationships between GDM gut microbiota at two times before and after the diet intervention during second trimester of pregnancy and clinical characteristics in cohort of GDM women. We found that short-term diet management in GDM processes is associated with changes in the Firmicutes/Bacteroidetes ratio and some specific taxa rather than an alternative gut microbial pattern. Our study highlights the importance of considering diet intervention as the rescue of microbial dysfunction of GDM disease and can serve as a strategy for early prevention in future study.

Effect of a Mediterranean diet intervention on gastrointestinal function in Parkinson’s disease (the MEDI-PD study): study protocol for a randomised controlled trial

IntroductionConstipation is a common and sometimes debilitating non-motor symptom of Parkinson’s disease (PD) that can result in intestinal inflammation and microbial dysbiosis. The Mediterranean diet, rich in fermentable fibres and anti-inflammatory phenolic compounds, is associated with reduced risk of developing PD and slower progression of parkinsonism. The Mediterranean diet is often recommended for people with PD; however, no studies to date examine this diet as a therapeutic intervention to modulate gastrointestinal (GI) dysfunction.Methods and analysisThis is a randomised, controlled, parallel study. During a 2-week run-in, participants with PD and constipation symptoms (n=52) will undergo baseline nutritional and neurological assessments and provide a stool sample. Participants will be stratified by sex and Hoehn and Yahr stage and randomised to follow standard of care for constipation (control) or standard of care plus a Mediterranean diet (intervention) for 8 weeks. A study dietitian will provide dietary instruction and weekly follow-up via telephone to both groups to support adherence and monitor adverse events. Questionnaires will assess dietary intake and GI function including stool frequency, form, symptoms and laxative usage. Measurements completed at baseline will be repeated at 4 and 8 weeks of the intervention. The primary outcome is to evaluate the difference between mean change (final–baseline) in Gastrointestinal Symptom Rating Scale (GSRS) constipation syndrome scores for the control versus intervention groups. Secondary outcomes will assess stool frequency and form, weekly GSRS syndrome scores, digestive quality of life, laxative usage, faecal microbial communities and inflammatory markers, anxiety, depression, quality life, body weight and composition, dietary fibre intake and Mediterranean diet adherence.Ethics and disseminationThe study has received University of Florida Institutional Review Board-01 approval (IRB202001333). Findings will be disseminated via conference presentations, lectures and peer-reviewed publications.Trial registration numberNCT04683900.