Progress towards a targeted biorefinery of Chromochloris zofingiensis: a review.

Biorefinery approaches offer the potential to improve the economics of the microalgae industry by producing multiple products from a single source of biomass. Chromochloris zofingiensis shows great promise for biorefinery due to high biomass productivity and a diverse range of products including secondary carotenoids, predominantly astaxanthin; lipids such as TAGs; carbohydrates including starch; and proteins and essential amino acids. Whilst this species has been demonstrated to accumulate multiple products, the development of an integrated downstream process to obtain these is lacking. The objective of this review paper is to assess the research that has taken place and to identify the steps that must be taken to establish a biorefinery approach for C. zofingiensis. In particular, the reasons why C. zofingiensis is a promising species to target for biorefinery are discussed in terms of cellular structure, potential products, and means to accumulate desirable components via the alteration of culture conditions. Future advances and the challenges that lie ahead for successful biorefinery of this species are also reviewed along with potential solutions to address them. Supplementary Information: The online version contains supplementary material available at 10.1007/s13399-022-02955-7.

Transcranial magnetic stimulation input-output curve slope differences suggest variation in recruitment across muscle representations in primary motor cortex.

Measurement of the input-output (IO) curves of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) can be used to assess corticospinal excitability and motor recruitment. While IO curves have been used to study disease and pharmacology, few studies have compared the IO curves across the body. This study sought to characterize IO curve parameters across the dominant and non-dominant sides of upper and lower limbs in healthy participants. Laterality preferences were assessed in eight healthy participants and IO curves were measured bilaterally for the first dorsal interosseous (FDI), biceps brachii (BB), and tibialis anterior (TA) muscles. Results show that FDI has lower motor threshold than BB which is, in turn, lower than TA. In addition, both BB and TA have markedly shallower logarithmic IO curve slopes from small to large MEP responses than FDI. After normalizing these slopes by their midpoints to account for differences in motor thresholds, which could result from geometric factors such as the target depth, large differences in logarithmic slopes remain present between all three muscles. The differences in slopes between the muscles could not be explained by differences in normalized IO curve spreads, which relate to the extent of the cortical representation and were comparable across the muscles. The IO curve differences therefore suggest muscle-dependent variations in TMS-evoked recruitment across the primary motor cortex, which should be considered when utilizing TMS-evoked MEPs to study disease states and treatment effects.

JAG consensus statements for training and certification in colonoscopy.

Introduction: In the UK, endoscopy certification is awarded when trainees attain minimum competency standards for independent practice. A national evidence-based review was undertaken to update and develop standards and recommendations for colonoscopy training and certification. Methods: Under the oversight of the Joint Advisory Group (JAG), a modified Delphi process was conducted between 2019 and 2020 with multisociety expert representation. Following literature review and Grading of Recommendations, Assessment, Development and Evaluations appraisal, recommendation statements on colonoscopy training and certification were formulated and subjected to anonymous voting to obtain consensus. Accepted statements were peer reviewed by JAG and relevant stakeholders for incorporation into the updated colonoscopy certification pathway. Results: In total, 45 recommendation statements were generated under the domains of: definition of competence (13), acquisition of competence (20), assessment of competence (8) and postcertification support (4). The consensus process led to revised criteria for colonoscopy certification, comprising: (1) achieving key performance indicators defined within British Society of Gastroenterology standards (ie, unassisted caecal intubation rate >90%, rectal retroversion >90%, polyp detection rate >15%+, polyp retrieval rate >90%, patient comfort <10% with moderate-severe discomfort); (2) minimum procedure count 280+; (3) performing 15+ procedures over the preceding 3 months; (4) attendance of the JAG Basic Skills in Colonoscopy course; (5) terminal ileal intubation rates of 60%+ in inflammatory bowel disease; (6) satisfying requirements for formative direct observation of procedure skills (DOPS) and direct observation of polypectomy skills (Size, Morphology, Site, Access (SMSA) level 2); (7) evidence of reflective practice as documented on the JAG Endoscopy Training System reflection tool; (8) successful performance in summative DOPS. Conclusion: The UK standards for training and certification in colonoscopy have been updated, culminating in a single-stage certification process with emphasis on polypectomy competency (SMSA Level 2+). These standards are intended to support training, improve standards of colonoscopy and polypectomy, and provide support to the newly independent practitioner.

JAG consensus statements for training and certification in flexible sigmoidoscopy.

Introduction: Joint Advisory Group (JAG) certification in endoscopy is awarded when trainees attain minimum competency standards for independent practice. A national evidence-based review was undertaken to update standards for training and certification in flexible sigmoidoscopy (FS). Methods: A modified Delphi process was conducted between 2019 and 2020 with multisociety representation from experts and trainees. Following literature review and Grading of Recommendations, Assessment, Development and Evaluations appraisal, recommendation statements on FS training and certification were formulated and subjected to anonymous voting to obtain consensus. Accepted statements were peer-reviewed by national stakeholders for incorporation into the JAG FS certification pathway. Results: In total, 41 recommendation statements were generated under the domains of: definition of competence (13), acquisition of competence (17), assessment of competence (7) and postcertification support (4). The consensus process led to revised criteria for colonoscopy certification, comprising: (A) achieving key performance indicators defined within British Society of Gastroenterology standards (ie, rectal retroversion >90%, polyp retrieval rate >90%, patient comfort <10% with moderate-severe discomfort); (B) minimum procedure count ≥175; (C) performing 15+ procedures over the preceding 3 months; (D) attendance of the JAG Basic Skills in Lower gastrointestinal Endoscopy course; (E) satisfying requirements for formative direct observation of procedural skill (DOPS) and direct observation of polypectomy skill (SMSA level 1); (F) evidence of reflective practice as documented on the JAG Endoscopy Training System reflection tool and (G) successful performance in summative DOPS. Conclusion: The UK standards for training and certification in FS have been updated to support training, uphold standards in FS and polypectomy, and provide support to the newly independent practitioner.

Wild blueberry (poly)phenols can improve vascular function and cognitive performance in healthy older individuals: a double-blind randomized controlled trial.

BACKGROUND: Evidence suggests that the intake of blueberry (poly)phenols is associated with improvements in vascular function and cognitive performance. Whether these cognitive effects are linked to increases in cerebral and vascular blood flow or changes in the gut microbiota is currently unknown. METHODS: A double-blind, parallel randomized controlled trial was conducted in 61 healthy older individuals aged 65-80 y. Participants received either 26 g of freeze-dried wild blueberry (WBB) powder (302 mg anthocyanins) or a matched placebo (0 mg anthocyanins). Endothelial function measured by flow-mediated dilation (FMD), cognitive function, arterial stiffness, blood pressure (BP), cerebral blood flow (CBF), gut microbiome, and blood parameters were measured at baseline and 12 wk following daily consumption. Plasma and urinary (poly)phenol metabolites were analyzed using microelution solid-phase extraction coupled with liquid chromatography-mass spectrometry. RESULTS: A significant increase in FMD and reduction in 24 h ambulatory systolic BP were found in the WBB group compared with the placebo group (0.86%; 95% CI: 0.56, 1.17, P < 0.001; -3.59 mmHg; 95% CI: -6.95, -0.23, P = 0.037; respectively). Enhanced immediate recall on the auditory verbal learning task, alongside better accuracy on a task-switch task was also found following WBB treatment compared with placebo (P < 0.05). Total 24 h urinary (poly)phenol excretion increased significantly in the WBB group compared with placebo. No changes in the CBF or gut microbiota composition were found. CONCLUSIONS: Daily intake of WBB powder, equivalent to 178 g fresh weight, improves vascular and cognitive function and decreases 24 h ambulatory systolic BP in healthy older individuals. This suggests that WBB (poly)phenols may reduce future CVD risk in an older population and may improve episodic memory processes and executive functioning in older adults at risk for cognitive decline. Clinical Trial Registration number in clinicaltrials.gov: NCT04084457.

Comparison between dietary assessment methods and biomarkers in estimating dietary (poly)phenol intake.

Background: although widely used, there is limited understanding of the suitability of different dietary assessment tools to estimate (poly)phenol intake. This study aims to compare the agreement between a food frequency questionnaire (FFQ) and a 7-day food diary (7DD) in assessing (poly)phenol intake and explore their associations with the urinary and plasma (poly)phenol metabolites. Methods: healthy free-living participants aged 18-80 years (n = 413) completed a 7DD and an FFQ (EPIC-Norfolk) and provided a 24 h urine and a fasting plasma sample. A comprehensive in-house (poly)phenol database was used to estimate (poly)phenol intake. The phenolic metabolite levels were analysed using a validated LC-MS method. The agreement between dietary assessment methods and biomarkers were evaluated by intraclass correlation coefficients (ICC), weighted kappa, quartile classification, Bland-Altman plots and correlations. Results: the total (poly)phenol intake estimated from FFQ was higher than from 7DD (median 1463 and 1042 mg d-1, respectively). The agreement between FFQ and 7DD were moderate (ICC 0.51-0.59) for total (poly)phenols, flavan-3-ols, total phenolic acids, hydroxycinnamic acids and alkylmethoxyphenols, and were poor for all the other classes and subclasses (ICC 0.00-0.48). Positive correlations with total urine phenolic metabolites were found in FFQ estimated anthocyanins, dihydroflavonols, total lignans, tyrosols, alkylmethoxyphenols, total phenolic acids, and total stilbenes and the 7DD estimated theaflavins and thearubigins (all FDR adjusted p values < 0.1). No significant correlations were found between total plasma phenolic metabolites and (poly)phenol intake. Conclusion: agreements between dietary assessment tools were moderate for the major classes of (poly)phenols, while agreements between (poly)phenol intake and biomarkers were poor. Future research using biomarker approaches to increase the accuracy of estimating (poly)phenol exposure in larger populations is needed.

TAP: targeting and analysis pipeline for optimization and verification of coil placement in transcranial magnetic stimulation.

Objective.Transcranial magnetic stimulation (TMS) can modulate brain function via an electric field (E-field) induced in a brain region of interest (ROI). The ROI E-field can be computationally maximized and set to match a specific reference using individualized head models to find the optimal coil placement and stimulus intensity. However, the available software lacks many practical features for prospective planning of TMS interventions and retrospective evaluation of the experimental targeting accuracy.Approach.The TMS targeting and analysis pipeline (TAP) software uses an MRI/fMRI-derived brain target to optimize coil placement considering experimental parameters such as the subject's hair thickness and coil placement restrictions. The coil placement optimization is implemented in SimNIBS 3.2, for which an additional graphical user interface (TargetingNavigator) is provided to visualize/adjust procedural parameters. The coil optimization process also computes the E-field at the target, allowing the selection of the TMS device intensity setting to achieve specific E-field strengths. The optimized coil placement information is prepared for neuronavigation software, which supports targeting during the TMS procedure. The neuronavigation system can record the coil placement during the experiment, and these data can be processed in TAP to quantify the accuracy of the experimental TMS coil placement and induced E-field.Main results.TAP was demonstrated in a study consisting of three repetitive TMS sessions in five subjects. TMS was delivered by an experienced operator under neuronavigation with the computationally optimized coil placement. Analysis of the experimental accuracy from the recorded neuronavigation data indicated coil location and orientation deviations up to about 2 mm and 2°, respectively, resulting in an 8% median decrease in the target E-field magnitude compared to the optimal placement.Significance.TAP supports navigated TMS with a variety of features for rigorous and reproducible stimulation delivery, including planning and evaluation of coil placement and intensity selection for E-field-based dosing.

Improving safety and reducing error in endoscopy (ISREE): a survey of UK services.

BACKGROUND: The Joint Advisory Group on Gastrointestinal Endoscopy (JAG) 'Improving Safety and Reducing Error in Endoscopy' (ISREE) strategy was developed in 2018. In line with the strategy, a survey was conducted within the JAG census in 2019 to gain further insights and understanding of key safety-related areas within UK endoscopy. METHODS: Questions were developed using the ISREE strategy as a guide and adapted by key JAG stakeholders. They were incorporated into the 2019 JAG census of UK endoscopy services. Quantitative and qualitative statistical methods were employed to analyse the results. RESULTS: There was a 68% response rate. There was regional variability in the provision of out-of-hours GIB services (p<0.001). Across 1 month, 1535 incidents were reported across all services. There was a significantly higher proportion of reported incidents in acute services compared with others (p<0.001). Technical and training incidents were likely to be reported significantly differently to all other incident types. 74% of services have an endoscopy-specific sedation policy and 42% have a named sedation or anaesthetic lead for endoscopy. Services highlighted a desire for more anaesthetic-supported lists. Only 66% of services stated they have an effective strategy for supporting upskilling of endoscopists. Across acute services, 56% have access to human factors and endoscopic non-technical skills (ENTS) training. Patient feedback is used in several ways to improve services, develop training and promote shared learning among endoscopy users. CONCLUSIONS: The census provides a benchmark for key safety-related characteristics of endoscopy services. These results have highlighted key areas to develop, guided by the ISREE strategy.

Network-based rTMS to modulate working memory: The difficult choice of effective parameters for online interventions.

BACKGROUND: Online repetitive transcranialmagnetic stimulation (rTMS) has been shown to modulate working memory (WM) performance in a site-specific manner, with behavioral improvements due to stimulation of the dorsolateral prefrontal cortex (DLPFC), and impairment from stimulation to the lateral parietal cortex (LPC). Neurobehavioral studies have demonstrated that subprocesses of WM allowing for the maintenance and manipulation of information in the mind involve unique cortical networks. Despite promising evidence of modulatory effects of rTMS on WM, no studies have yet demonstrated distinct modulatory control of these two subprocesses. The current study therefore sought to explore this possibility through site-specific stimulation during an online task invoking both skills. METHODS: Twenty-nine subjects completed a 4-day protocol, in which active or sham 5Hz rTMS was applied over the DLPFC and LPC in separate blocks of trials while participants performed tasks that required either maintenance alone, or both maintenance and manipulation (alphabetization) of information. Stimulation targets were defined individually based on fMRI activation and structural network properties. Stimulation amplitude was adjusted using electric field modeling to equate induced current in the target region across participants. RESULTS: Despite the use of advanced techniques, no significant differences or interactions between active and sham stimulation were found. Exploratory analyses testing stimulation amplitude, fMRI activation, and modal controllability showed nonsignificant but interesting trends with rTMS effects. CONCLUSION: While this study did not reveal any significant behavioral changes in WM, the results may point to parameters that contribute to positive effects, such as stimulation amplitude and functional activation.

Algae biostimulants: A critical look at microalgal biostimulants for sustainable agricultural practices.

For the growing human population to be sustained during present climatic changes, enhanced quality and quantity of crops are essential to enable food security worldwide. The current consensus is that we need to make a transition from a petroleum-based to a bio-based economy via the development of a sustainable circular economy and biorefinery approaches. Both macroalgae (seaweeds) and microalgae have been long considered a rich source of plant biostimulants with an attractive business opportunity in agronomy and agro-industries. To date, macroalgae biostimulants have been well explored. In contrast, microalgal biostimulants whilst known to have positive effects on development, growth and yields of crops, their commercial implementation is constrained by lack of research and cost of production. The present review highlights the current knowledge on potential biostimulatory compounds, key sources and their quantitative information from algae. Specifically, we provide an overview on the prospects of microalgal biostimulants to advance crop production and quality. Key aspects such as specific biostimulant effects caused by extracts of microalgae, feasibility and potential of co-cultures and later co-application with other biostimulants/biofertilizers are highlighted. An overview of the current knowledge, recent advances and achievements on extraction techniques, application type, application timing, current market and regulatory aspects are also discussed. Moreover, aspects involved in circular economy and biorefinery approaches are also covered, such as: integration of waste resources and implementation of high-throughput phenotyping and -omics tools in isolating novel strains, exploring synergistic interactions and illustrating the underlying mode of microalgal biostimulant action. Overall, this review highlights the current and future potential of microalgal biostimulants, algal biochemical components behind these traits and finally bottlenecks and prospects involved in the successful commercialisation of microalgal biostimulants for sustainable agricultural practices.

Towards a circular economy: A novel microalgal two-step growth approach to treat excess nutrients from digestate and to produce biomass for animal feed.

Implementing a circular economy aimed at reusing resources is becoming increasingly important for industry. Microalgae fit within a circular economy by being able to bioremediate nutrient waste and as a source of biomass for several commercial applications. Here, we report a novel validation of a circular economy concept using microalgae at a relevant industrial scale with a new two-phase process. During the first phase biomass was grown autotrophically, biomass was then concentrated using membrane technology for the second phase where mixotrophic conditions were applied to boost growth further. Microalgae cultures were able to grow (13.8 g/L), uptake and bioremediate nutrients (Nitrogen > 134 mg/L/day) from an anaerobic digestion side-stream (digestate), obtaining high quality microalgae biomass (>45% protein content) suitable for use as animal feed, closing the circular economy loop for industrial applications.

Valorising nutrient-rich digestate: Dilution, settlement and membrane filtration processing for optimisation as a waste-based media for microalgal cultivation.

Digestate produced from the anaerobic digestion of food and farm waste is primarily returned to land as a biofertiliser for crops, with its potential to generate value through alternative processing methods at present under explored. In this work, valorisation of a digestate resulting from the treatment of kitchen and food waste was investigated, using dilution, settlement and membrane processing technology. Processed digestate was subsequently tested as a nutrient source for the cultivation of Chlorella vulgaris, up to pilot-scale (800L). Dilution of digestate down to 2.5% increased settlement rate and induced release of valuable compounds for fertiliser usage such as nitrogen and phosphorus. Settlement, as a partial processing of digestate offered a physical separation of liquid and solid fractions at a low cost. Membrane filtration demonstrated efficient segregation of nutrients, with micro-filtration recovering 92.38% of phosphorus and the combination of micro-filtration, ultra-filtration, and nano-filtration recovering a total of 94.35% of nitrogen from digestate. Nano-filtered and micro-filtered digestates at low concentrations were suitable substrates to support growth of Chlorella vulgaris. At pilot-scale, the microalgae grew successfully for 28 days with a maximum growth rate of 0.62 day-1 and dry weight of 0.86  g⋅L-1. Decline in culture growth beyond 28 days was presumably linked to ammonium and heavy metal accumulation in the cultivation medium. Processed digestate provided a suitable nutrient source for successful microalgal cultivation at pilot-scale, evidencing potential to convert excess nutrients into biomass, generating value from excess digestate and providing additional markets to the anaerobic digestion sector.

Blueberries and cardiovascular disease prevention.

Blueberries are a rich source of (poly)phenols, particularly anthocyanins. Epidemiological studies indicate that anthocyanin-rich foods including blueberries are associated with a reduction in the risk of cardiovascular disease. These observational findings are supported by a number of randomized-controlled trials showing improvements in biomarkers of cardiovascular disease risk. The beneficial effects of blueberry (poly)phenols are particularly clear when measuring flow-mediated dilation over various timeframes and study populations. However, other outcomes are less clear, such as effects on blood pressure, arterial stiffness and blood lipid profile. This may be due to the heterogeneity existing in study designs, such as duration of the intervention, and the health status of participants. Longer-term RCTs using gold standard methods in relevant populations which can be translated to the general public are needed to clarify and strengthen the evidence available. While circulating phenolic blueberry metabolites have been linked with improvements in vascular function, the biological activities and mechanisms of action of individual metabolites and their interaction in vivo are still unknown. Evaluating the bioactivities of metabolites alone and together, and analysing their structure-activity relationship in well-designed and physiologically relevant experimental and human studies are needed to understand the mechanisms of how these metabolites affect vascular function.

Diabetes Mobile Care: Aggregating and Visualizing Data from Multiple Mobile Health Technologies.

As the appeal and use of mobile health (mHealth) technologies continues to grow, where does mHealth fit into clinical practice? This article explores the approach and obstacles encountered when integrating mHealth data into existing clinical frameworks and explores data visualization design tradeoffs. Specifically, this paper discusses the successes and challenges that arose when using commercial mHealth technologies, synthesizing multiple mHealth device data, and tailoring visualizations based on iterative feedback from type II diabetes mellitus patients. This research aims to influence the development of patient portals within electronic health records by understanding and addressing the challenges involved in acquiring, interpreting, and displaying this data set. In particular, we need to ensure that the presentation of these data is accessible and understandable by diverse populations.

Improving safety and reducing error in endoscopy: simulation training in human factors.

Patient safety incidents occur throughout healthcare and early reports have exposed how deficiencies in 'human factors' have contributed to mortality in endoscopy. Recognising this, in the UK, the Joint Advisory Group for Gastrointestinal Endoscopy have implemented a number of initiatives including the 'Improving Safety and Reducing Error in Endoscopy' (ISREE) strategy. Within this, simulation training in human factors and Endoscopic Non-Technical Skills (ENTS) is being developed. Across healthcare, simulation training has been shown to improve team skills and patient outcomes. Although the literature is sparse, integrated and in situ simulation modalities have shown promise in endoscopy. Outcomes demonstrate improved individual and team performance and development of skills that aid clinical practice. Additionally, the use of simulation training to detect latent errors in the working environment is of significant value in reducing error and preventing harm. Implementation of simulation training at local and regional levels can be successfully achieved with collaboration between organisational, educational and clinical leads. Nationally, simulation strategies are a key aspect of the ISREE strategy to improve ENTS training. These may include integration of simulation into current training or development of novel simulation-based curricula. However used, it is evident that simulation training is an important tool in developing safer endoscopy.

Enhancing Diabetes Self-Management Through Collection and Visualization of Data From Multiple Mobile Health Technologies: Protocol for a Development and Feasibility Trial.

BACKGROUND: Self-management is integral for control of type 2 diabetes mellitus (T2DM). Patient self-management is improved when they receive real-time information on their health status and behaviors and ongoing facilitation from health professionals. However, timely information for these behaviors is notably absent in the health care system. Providing real-time data could help improve patient understanding of the dynamics of their illness and assist clinicians in developing targeted approaches to improve health outcomes and in delivering personalized care when and where it is most needed. Mobile technologies (eg, wearables, apps, and connected scales) have the potential to make these patient-provider interactions a reality. What strategies might best help patients overcome self-management challenges using self-generated diabetes-related data? How might clinicians effectively guide patient self-management with the advantage of real-time data? OBJECTIVE: This study aims to describe the protocol for an ongoing study (June 2016-May 2019) that examines trajectories of symptoms, health behaviors, and associated challenges among individuals with T2DM utilizing multiple mobile technologies, including a wireless body scale, wireless glucometer, and a wrist-worn accelerometer over a 6-month period. METHODS: We are conducting an explanatory sequential mixed methods study of 60 patients with T2DM recruited from a primary care clinic. Patients were asked to track relevant clinical data for 6 months using a wireless body scale, wireless glucometer, a wrist-worn accelerometer, and a medication adherence text message (short message service, SMS) survey. Data generated from the devices were then analyzed and visualized. A subset of patients is currently being interviewed to discuss their challenges and successes in diabetes self-management, and they are being shown visualizations of their own data. Following the data collection period, we will conduct interviews with study clinicians to explore ways in which they might collaborate with patients. RESULTS: This study has received regulatory approval. Patient enrollment ongoing with a sample size of 60 patients is complete, and up to 20 clinicians will be enrolled. At the patient level, data collection is complete, but data analysis is pending. At the clinician level, data collection is currently ongoing. CONCLUSIONS: This study seeks to expand the use of mobile technologies to generate real-time data to enhance self-management strategies. It also seeks to obtain both patient and provider perspectives on using real-time data to develop algorithms for software that will facilitate real-time self-management strategies. We expect that the findings of this study will offer important insight into how to support patients and providers using real-time data to manage a complex chronic illness. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13517.

Effects of aronia berry (poly)phenols on vascular function and gut microbiota: a double-blind randomized controlled trial in adult men.

BACKGROUND: Aronia melanocarpa is a rich source of (poly)phenols. Previous research has demonstrated that these berries may provide cardiovascular health benefits in high-risk populations. However, very few studies have investigated the effects of daily consumption of dietary achievable amounts of the berries in healthy subjects. OBJECTIVES: The aim of this study was to investigate the effects of aronia berries on vascular function and gut microbiota composition in a healthy population. METHODS: A double-blind, placebo-controlled, parallel designed study was conducted in 66 healthy men randomly allocated to consume a (poly)phenol-rich extract (116 mg, 75 g berries), a whole fruit powder (12 mg, 10 g berries), or placebo (maltodextrin) for 12 wk. Flow-mediated dilation (FMD), arterial stiffness, blood pressure, heart rate, and serum biochemistry were assessed. Plasma (poly)phenol metabolites were analyzed by LC-MS. Gut microbiota composition was determined via 16S rRNA sequencing in stool samples. RESULTS: Consumption of aronia whole fruit and extract powder for 12 wk led to a significant increase in FMD over control of 0.9% ± 0.4% (95% CI: 0.13%, 1.72%) and 1.2% ± 0.4% (95% CI: 0.36%, 1.97%), respectively. Acute improvements in FMD were also observed 2 h after consumption of aronia extract on day 1 (1.1% ± 0.3%, P = 0.003) and 12 wk later (1.5% ± 0.4%, P = 0.0001). Circulating plasma phenolic metabolites increased upon consumption of the aronia treatments. Although no changes were found in gut microbiota diversity, consumption of aronia extract increased the growth of Anaerostipes (+10.6%, P = 0.01), whereas aronia whole fruit showed significant increases in Bacteroides (+193%, P = 0.01). Correlation analysis identified significant associations between changes in FMD, aronia-derived phenolic metabolites, and specific gut microbial genera. CONCLUSIONS: In healthy men, consumption of aronia berry (poly)phenols improved endothelial function and modulated gut microbiota composition, indicating that regular aronia consumption has the potential to maintain cardiovascular health in individuals at low risk of cardiovascular disease. This trial was registered at CLINICALTRIALs.gov as NCT03041961.