Polyphenols are compounds found in foods such as tea, coffee, cocoa, olive oil, and red wine and have been studied to determine if their intake may modify cardiovascular disease (CVD) risk. ...Historically, biologic actions of polyphenols have been attributed to antioxidant activities, but recent evidence suggests that immunomodulatory and vasodilatory properties of polyphenols may also contribute to CVD risk reduction. These properties will be discussed, and recent epidemiological evidence and intervention trials will be reviewed. Further identification of polyphenols in foods and accurate assessment of exposures through measurement of biomarkers (i.e., polyphenol metabolites) could provide the needed impetus to examine the impact of polyphenol-rich foods on CVD intermediate outcomes (especially those signifying chronic inflammation) and hard endpoints among high risk patients. Although we have mechanistic insight into how polyphenols may function in CVD risk reduction, further research is needed before definitive recommendations for consumption can be made.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
One way to improve both the ecological performance and functionality of probiotic bacteria is by combining them with a prebiotic in the form of a synbiotic. However, the degree to which such ...synbiotic formulations improve probiotic strain functionality in humans has not been tested systematically. Our goal was to use a randomized, double-blind, placebo-controlled, parallel-arm clinical trial in obese humans to compare the ecological and physiological impact of the prebiotic galactooligosaccharides (GOS) and the probiotic strains Bifidobacterium adolescentis IVS-1 (autochthonous and selected via in vivo selection) and Bifidobacterium lactis BB-12 (commercial probiotic allochthonous to the human gut) when used on their own or as synbiotic combinations. After 3 weeks of consumption, strain-specific quantitative real-time PCR and 16S rRNA gene sequencing were performed on fecal samples to assess changes in the microbiota. Intestinal permeability was determined by measuring sugar recovery in urine by GC after consumption of a sugar mixture. Serum-based endotoxin exposure was also assessed.
IVS-1 reached significantly higher cell numbers in fecal samples than BB-12 (P < 0.01) and, remarkably, its administration induced an increase in total bifidobacteria that was comparable to that of GOS. Although GOS showed a clear bifidogenic effect on the resident gut microbiota, both probiotic strains showed only a non-significant trend of higher fecal cell numbers when administered with GOS. Post-aspirin sucralose:lactulose ratios were reduced in groups IVS-1 (P = 0.050), IVS-1 + GOS (P = 0.022), and GOS (P = 0.010), while sucralose excretion was reduced with BB-12 (P = 0.002) and GOS (P = 0.020), indicating improvements in colonic permeability but no synergistic effects. No changes in markers of endotoxemia were observed.
This study demonstrated that "autochthony" of the probiotic strain has a larger effect on ecological performance than the provision of a prebiotic substrate, likely due to competitive interactions with members of the resident microbiota. Although the synbiotic combinations tested in this study did not demonstrate functional synergism, our findings clearly showed that the pro- and prebiotic components by themselves improved markers of colonic permeability, providing a rational for their use in pathologies with an underlying leakiness of the gut.
A pro-inflammatory intestinal microbiome is characteristic of Parkinson's disease (PD). Prebiotic fibers change the microbiome and this study sought to understand the utility of prebiotic fibers for ...use in PD patients. The first experiments demonstrate that fermentation of PD patient stool with prebiotic fibers increased the production of beneficial metabolites (short chain fatty acids, SCFA) and changed the microbiota demonstrating the capacity of PD microbiota to respond favorably to prebiotics. Subsequently, an open-label, non-randomized study was conducted in newly diagnosed, non-medicated (n = 10) and treated PD participants (n = 10) wherein the impact of 10 days of prebiotic intervention was evaluated. Outcomes demonstrate that the prebiotic intervention was well tolerated (primary outcome) and safe (secondary outcome) in PD participants and was associated with beneficial biological changes in the microbiota, SCFA, inflammation, and neurofilament light chain. Exploratory analyses indicate effects on clinically relevant outcomes. This proof-of-concept study offers the scientific rationale for placebo-controlled trials using prebiotic fibers in PD patients. ClinicalTrials.gov Identifier: NCT04512599.
Opioid misuse and addiction are a public health crisis resulting in debilitation, deaths, and significant social and economic impact. Curbing this crisis requires collaboration among academic, ...government, and industrial partners toward the development of effective nonaddictive pain medications, interventions for opioid overdose, and addiction treatments. A 2-day meeting,
, was held at the National Institutes of Health (NIH) to address these concerns and to chart a collaborative path forward. The meeting was supported by the NIH Helping to End Addiction Long-Term
(HEAL) Initiative, an aggressive, trans-agency effort to speed scientific solutions to stem the national opioid crisis. The event was unique in bringing together two research disciplines, addiction and pain, in order to create a forum for crosscommunication and collaboration. The output from the symposium will be considered by the HEAL Initiative; this article summarizes the scientific presentations and key takeaways. Improved understanding of the etiology of acute and chronic pain will enable the discovery of novel targets and regulatable pain circuits for safe and effective therapeutics, as well as relevant biomarkers to ensure adequate testing in clinical trials. Applications of improved technologies including reagents, assays, model systems, and validated probe compounds will likely increase the delivery of testable hypotheses and therapeutics to enable better health outcomes for patients. The symposium goals were achieved by increasing interdisciplinary collaboration to accelerate solutions for this pressing public health challenge and provide a framework for focused efforts within the research community. SIGNIFICANCE STATEMENT: This article summarizes key messages and discussions resulting from a 2-day symposium focused on challenges and opportunities in developing addiction- and pain-related medications. Speakers and attendees came from 40 states in the United States and 15 countries, bringing perspectives from academia, industry, government, and healthcare by researchers, clinicians, regulatory experts, and patient advocates.
Parkinson's Disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra. Recent evidence supports the involvement of the gastrointestinal tract ...in PD pathogenesis, including alterations in microbiota and intestinal permeability. Apart from being the preferred energy source for colonic epithelial cells, butyrate is involved in anti-inflammatory, enteroendocrine and epigenetic mechanisms that influence colonic and systemic health, including brain function. A few studies using oral administration of sodium butyrate indicate beneficial effects in PD animal models; however, prebiotic fibers that generate butyrate locally in the gut may be more effective. The design and selection of butyrogenic prebiotic fibers would allow preclinical studies to evaluate how gut-derived butyrate could affect PD pathophysiology. This review describes potential benefits of increasing gut butyrate production in PD through a prebiotic approach. Moreover, physico-chemical features of prebiotic fibers that target butyrogenic colonic bacteria are discussed.
Individuals of admixed ancestries (for example, African Americans) inherit a mosaic of ancestry segments (local ancestry) originating from multiple continental ancestral populations. This offers the ...unique opportunity of investigating the similarity of genetic effects on traits across ancestries within the same population. Here we introduce an approach to estimate correlation of causal genetic effects (r
) across local ancestries and analyze 38 complex traits in African-European admixed individuals (N = 53,001) to observe very high correlations (meta-analysis r
= 0.95, 95% credible interval 0.93-0.97), much higher than correlation of causal effects across continental ancestries. We replicate our results using regression-based methods from marginal genome-wide association study summary statistics. We also report realistic scenarios where regression-based methods yield inflated heterogeneity-by-ancestry due to ancestry-specific tagging of causal effects, and/or polygenicity. Our results motivate genetic analyses that assume minimal heterogeneity in causal effects by ancestry, with implications for the inclusion of ancestry-diverse individuals in studies.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
7.
Prebiotics and Inflammatory Bowel Disease Rasmussen, Heather E; Hamaker, Bruce R
Gastroenterology clinics of North America,
12/2017, Volume:
46, Issue:
4
Journal Article
Peer reviewed
Open access
Dietary fiber, specifically prebiotics, is the primary source of energy for the gut microbiota and thus has the potential to beneficially modify microbiota composition. Prebiotics have been used in ...both in vitro studies and with animal models of colitis with largely positive results. Human studies are few and have been conducted with only a few select prebiotics, primarily fructan-containing fibers. Although disease activity and inflammatory markers have improved, more needs to be learned about the specific prebiotic compounds and how they can be used to best improve the gut microbiota to counter changes induced by inflammatory bowel disease.
The epidemy of metabolic syndrome (MetS) is typically preceded by adoption of a "risky" lifestyle (e.g., dietary habit) among populations. Evidence shows that those with low socioeconomic status ...(SES) are at an increased risk for MetS. To investigate this, we recruited 123 obese subjects (body mass index BMI ≥ 30) from Chicago. Multi-omic data were collected to interrogate fecal microbiota, systemic markers of inflammation and immune activation, plasma metabolites, and plasma glycans. Intestinal permeability was measured using the sugar permeability testing. Our results suggest a heterogenous metabolic dysregulation among obese populations who are at risk of MetS. Systemic inflammation, linked to poor diet, intestinal microbiome dysbiosis, and gut barrier dysfunction may explain the development of MetS in these individuals. Our analysis revealed 37 key features associated with increased numbers of MetS features. These features were used to construct a composite metabolic-inflammatory (MI) score that was able to predict progression of MetS among at-risk individuals. The MI score was correlated with several markers of poor diet quality as well as lower levels of gut microbial diversity and abnormalities in several species of bacteria. This study reveals novel targets to reduce the burden of MetS and suggests access to healthy food options as a practical intervention.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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