scholarly journals Heterogeneity in statin responses explained by variation in the human gut microbiome

2021 ◽  
Author(s):  
Tomasz Wilmanski ◽  
Sergey A. Kornilov ◽  
Christian Diener ◽  
Mathew Conomos ◽  
Jennifer C. Lovejoy ◽  
...  
Keyword(s):  
Side Effects ◽  
Statin Therapy ◽  
Gut Microbiome ◽  
Metabolic Health ◽  
Atherosclerotic Cardiovascular Disease ◽  
Microbiome Composition ◽  
Increased Risk ◽  
Statin Use ◽  
Target Effects ◽  
Health Parameters

AbstractStatins remain one of the most prescribed medications worldwide. While effective in decreasing atherosclerotic cardiovascular disease risk, statin use is associated with several side effects for a subset of patients, including disrupted metabolic control and increased risk of type II diabetes. We investigated the potential role of the gut microbiome in modifying patient response to statin therapy. In a cohort of >1840 individuals, we find that the hydrolyzed substrate for 3-hydroxy-3-methylglutarate-CoA (HMG-CoA) reductase, HMG, may serve as a reliable marker for statin on-target effects. Through exploring gut microbiome associations between blood-derived measures of statin effectiveness and metabolic health parameters among statin users and non-users, we find that heterogeneity in statin response is associated with variation in the gut microbiome. A Bacteroides rich, α-diversity depleted, microbiome composition corresponds to the strongest statin on-target response, but also greatest disruption to glucose homeostasis, indicating lower treatment doses and/or complementary therapies may be beneficial in those individuals. Our findings suggest a potential path towards personalizing statin treatment through gut microbiome monitoring.Between 25% - 30% of older adults across the United States and Europe take statins regularly for the purpose of treating or preventing atherosclerotic cardiovascular disease (ACVD), making statins one of the most prescribed medications in the developed world 1,2. While statins have proven to be highly effective in decreasing ACVD-associated mortality, considerable heterogeneity exists in terms of efficacy (i.e., lowering low density lipoprotein (LDL) cholesterol) 3. Furthermore, statin use can give rise to a number of side effects in a subset of patients, including myopathy, disrupted glucose control, and increased risk of developing type II diabetes (T2D) 4–8. Several guidelines exist for which at-risk populations should be prescribed statins and at what intensity 9. However, despite considerable progress in identifying pharmacological 10 and genetic factors 11 contributing to heterogeneity in statin response, personalized approaches to statin therapy remain limited. Many times, treatment decisions are made through trial and error between the clinician and patient to obtain an optimal tolerable dose 12. Avoiding this trial-and-error phase through individualized analysis of genetic, physiological, and health parameters has the potential to improve drug tolerance, adherence, and long-term health benefits, as well as guide complementary therapies aimed at mitigating side effects.Several studies have recently demonstrated a link between the gut microbiome and statin use 13,14. Similar to other prescription drugs, statins are widely metabolized by gut bacteria into secondary compounds 15,16. This indicates that the gut microbiome may impact statin bioavailability or potency to its host, contributing to the interindividual variability in LDL response seen among statin users 17. Additionally, biochemical modification of statins by gut bacteria could potentially contribute to side effects of the drug 18. Independent of statins, the gut microbiome has a well characterized role in contributing to host metabolic health through regulating insulin sensitivity, blood glucose, and inflammation, hence sharing considerable overlap with off-target effects of statin therapy 19,20.Statin intake has also been implicated in shifting gut microbiome composition, where primarily obese individuals taking statins were less likely to be classified into a putative gut microbiome compositional state, or ‘enterotype’, defined by high relative abundance of Bacteroides and a depletion of short-chain fatty acid (SCFA) producing Firmicutes taxa 21. However, contradictory findings in animal models have also been reported, where a statin intervention decreased abundance of SCFA-producing taxa and, consequently, the gut ecosystem’s capacity to produce butyrate 22.Given the numerous documented interactions between the gut microbiome and statins, and the established effect of the gut microbiome on metabolic health, we sought to explore the potential role of the gut microbiome in modifying the effect of statins on inhibiting their target enzyme 3-hydroxy-3-methylglutarate-CoA (HMG-CoA) reductase, as well as influencing the negative side effects of statins on metabolic health parameters. We analyzed data from over 1840 deeply-phenotyped individuals with extensive medication histories, clinical laboratory tests, plasma metabolomics, whole genome and stool 16S rRNA gene amplicon sequencing data. We found that heterogeneity in statin on-target effects and off-target metabolic disruption could be explained by variation in the composition of the gut microbiome. Overall, our results suggest that, with further study and refinement, the taxonomic composition of the gut microbiome may be used to inform personalized statin therapies.

scholarly journals Shared Decisions: A Qualitative Study on Clinician and Patient Perspectives on Statin Therapy and Statin‐Associated Side Effects

2020 ◽  
Vol 9 (22) ◽  
Author(s):  
Sarah T. Ahmed ◽  
Julia M. Akeroyd ◽  
Dhruv Mahtta ◽  
Richard Street ◽  
Jason Slagle ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Decision Making ◽  
Side Effects ◽  
Statin Therapy ◽  
Decision Aid ◽  
Qualitative Interviews ◽  
High Risk Population ◽  
Atherosclerotic Cardiovascular Disease ◽  
Related Factors ◽  
Statin Use

Background Despite guideline recommendations and clinical trial data suggesting benefit, statin therapy use in patients with atherosclerotic cardiovascular disease remains suboptimal. The aim of this study was to understand clinician and patient views on statin therapy, statin‐associated side effects (SASEs), SASE management, and communication around statin risks and benefits. Methods and Results We conducted qualitative interviews of patients with atherosclerotic cardiovascular disease who had SASEs (n=17) and clinicians who regularly prescribe statins (n=20). We used directed content analysis, facilitated by Atlas.ti software, to develop and revise codebooks for clinician and patient interviews. The most relevant codes were “pile sorted” into 5 main topic domains: (1) SASEs vary in severity, duration, and time of onset; (2) communication practices by clinicians around statins and SASEs are variable and impacted by clinician time limitations and patient preconceived notions of SASEs; (3) although a “trial and error” approach to managing SASEs may be effective in allowing clinicians to keep patients with atherosclerotic cardiovascular disease on a statin, it can be frustrating for patients; (4) outside sources, such as the media, internet, social networks, and social circles, influence patients' perceptions and often impact the risk benefit discussion; and (5) a decision aid would be beneficial in facilitating clinician decision‐making around SASEs and discussion of SASEs with the patients. Conclusions Statin use among patients with atherosclerotic cardiovascular disease remains suboptimal because of various patient‐ and clinician‐related factors. The development of a decision aid to facilitate discussion of SASEs, clinician decision‐making, and SASE management may improve statin use in this high‐risk population.

Statin Use With the ATP III Guidelines Compared to the 2013 ACC/AHA Guidelines in HIV Primary Care Patients

2016 ◽  
Vol 30 (1) ◽  
pp. 64-69 ◽  
Author(s):  
Pansy Elsamadisi ◽  
Agnes Cha ◽  
Elise Kim ◽  
Safia Latif
Keyword(s):  
Statin Therapy ◽  
Retrospective Chart Review ◽  
Population Based ◽  
Risk Scores ◽  
Atherosclerotic Cardiovascular Disease ◽  
Laboratory Test Results ◽  
Hiv Primary Care ◽  
Cholesterol Guidelines ◽  
Level Of Agreement ◽  
Statin Use

Background: The 2013 Cholesterol Guidelines include a new atherosclerotic cardiovascular disease (ASCVD) risk calculator that determines the 10-year risk of coronary heart disease and/or stroke. The applicability of this calculator and its predecessor, the Framingham risk score (FRS) in Adult Treatment Panel (ATP) III, has been limited in patients with HIV. The objective of this study was to compare the risk scores of ASCVD and FRS in the initiation of statin therapy in patients with HIV. Methods: We conducted a retrospective chart review of patients with HIV on statin therapy from October 1, 2013, to April 1, 2014. Data collection included patient demographics, pertinent laboratory test results, and medication list. The primary end point evaluated the level of agreement between the guidelines. Results: Of 155 patients who met the inclusion criteria, 116 were treated similarly with both guidelines. This showed a moderate level of agreement ( P < .001). Forty-eight of 86 patients requiring statins were placed on the correct intensity statin using the 2013 guidelines. Regardless of which guideline, a majority of patients required statin therapy. Conclusion: A moderate agreement was found between both guidelines in terms of statin use when applied to an HIV patient population. Based on the 2013 guidelines and taking into account drug interactions with antiretrovirals, 44.2% of the patients were treated with an incorrect statin intensity.

scholarly journals Low statin use in nondialysis-dependent chronic kidney disease in the absence of clinical atherosclerotic cardiovascular disease or diabetes

2019 ◽  
Vol 12 (4) ◽  
pp. 530-537
Author(s):  
Talar W Markossian ◽  
Holly J Kramer ◽  
Nicholas J Burge ◽  
Ivan V Pacold ◽  
David J Leehey ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Atherosclerotic Cardiovascular Disease ◽  
Risk Equation ◽  
Diabetes Status ◽  
Increased Risk ◽  
Ascvd Risk ◽  
Risk Equivalent ◽  
Statin Use

Abstract Background Both reduced glomerular filtration rate and increased urine albumin excretion, markers of chronic kidney disease (CKD), are associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). However, CKD is not recognized as an ASCVD risk equivalent by most lipid guidelines. Statin medications, especially when combined with ezetimibe, significantly reduce ASCVD risk in patients with nondialysis-dependent CKD. Unless physicians recognize the heightened ASCVD risk in this population, statins may not be prescribed in the absence of clinical cardiovascular disease or diabetes, a recognized ASCVD risk equivalent. We examined statin use in adults with nondialysis-dependent CKD and examined whether the use differed in the presence of clinical ASCVD and diabetes. Methods This study ascertained statin use from pharmacy dispensing records during fiscal years 2012 and 2013 from the US Department of Veterans Affairs Healthcare System. The study included 581 344 veterans aged ≥50 years with nondialysis-dependent CKD Stages 3–5 with no history of kidney transplantation or dialysis. The 10-year predicted ASCVD risk was calculated with the pooled risk equation. Results Of veterans with CKD, 62.1% used statins in 2012 and 55.4% used statins continuously over 2 years (2012–13). Statin use in 2012 was 76.2 and 75.5% among veterans with CKD and ASCVD or diabetes, respectively, but in the absence of ASCVD, diabetes or a diagnosis of hyperlipidemia, statin use was 21.8% (P &lt; 0.001). The 10-year predicted ASCVD risk was ≥7.5% in 95.1% of veterans with CKD, regardless of diabetes status. Conclusions Statin use is low in veterans with nondialysis-dependent CKD in the absence of ASCVD or diabetes despite high-predicted ASCVD risk. Future studies should examine other populations.

scholarly journals Low total cholesterol is associated with increased major adverse cardiovascular events in men aged ≥70 years not taking statins

Heart ◽  
2019 ◽  
Vol 106 (9) ◽  
pp. 698-705 ◽  
Author(s):  
Sonali Rukshana Gnanenthiran ◽  
Austin C C Ng ◽  
Robert Cumming ◽  
David B Brieger ◽  
David Le Couteur ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Statin Therapy ◽  
Cardiovascular Events ◽  
Community Dwelling ◽  
Major Adverse Cardiovascular Events ◽  
Study Cohort ◽  
Increased Risk ◽  
Comorbidity Burden ◽  
Statin Use

ObjectiveLow levels of total cholesterol (TC) are associated with adverse outcomes in older populations. Whether this phenomenon is independent of statin use is unknown. We investigated the association between low TC levels and long-term major adverse cardiovascular events (MACE) in a prospective study of men aged ≥70 years without ischaemic heart disease (IHD) and whether this was influenced by statin use.MethodsThe CHAMP (Concord Health and Ageing in Men Project) cohort is a prospective cohort study of community-dwelling men aged ≥70 years. The relationship between TC and long-term MACE was analysed using Cox-regression modelling adjusted for comorbidities and stratified by statin use.ResultsThe study cohort comprised 1289 men (mean (±SD) age, 77.0±5.5 years; mean follow-up, 6.4±2.7 years). Decreasing TC level was associated with increased comorbidity burden, frailty and MACE (linear trend p<0.001). In men not on statin therapy (n=731), each 1 mmol/L decrease in TC was associated with increased MACE (HR 1.27, 95% CI 1.10 to 1.45, p=0.001) and mortality (HR 1.22, 95% CI 1.03 to 1.44, p=0.02) adjusted for comorbidities. In contrast, low TC in men on statins (n=558) was not associated with MACE (HR 0.91, 95% CI 0.74 to 1.11) or mortality (HR 0.86, 95% CI 0.68 to 1.09).ConclusionLow TC is associated with increased risk of MACE in older men without IHD who are not taking statin therapy but not in those on statins.

scholarly journals An insight into statin use and its association with muscular side effects in clinical practice

2015 ◽  
Vol 53 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Andreea Farcas ◽  
Camelia Bucsa ◽  
D. Leucuta ◽  
Cristina Mogosan ◽  
M. Bojita ◽  
...  
Keyword(s):  
Internal Medicine ◽  
Side Effects ◽  
Statin Therapy ◽  
Prospective Observational Study ◽  
Muscle Power ◽  
Statin Treatment ◽  
Lower Limbs ◽  
Time To Onset ◽  
Insight Into ◽  
Statin Use

Abstract Background. Muscular complaints are known side-effects of statin therapy, ranging from myalgia to clinically important myositis and rhabdomyolysis. We investigated the statin use and association with the presence and characteristics of muscular complaints. Methods. We conducted a prospective observational study in internal medicine departments. Patients with statin therapy before hospitalization were interviewed for muscular complaints. When muscular complaints were reported, information on type and severity of muscular symptoms, location and time to onset was collected. Results. We identified 85 patients with statin treatment at hospital admission out of 521 included. Nine (10.59%) patients reported muscular complaints associated with statin therapy. A cluster of symptoms (cramps, stiffness, decreased muscle power) was reported, affecting both upper and lower limbs. The severity of pain was in most of the cases moderate or severe. All patients reported that pain was intermittent. Five reported that pain was generalized. Symptoms appeared in the first month of treatment or three months after the drug initiation. Creatine kinase was raised in one patient. In two cases drug interactions were probably responsible for muscular complaints. Conclusion. In the studied set of patients muscular symptoms were a rather frequent effect of statin therapy. As this side-effect could be troublesome for patients and could lead to more severe outcomes, their timely detection and management is important.

scholarly journals Systems analysis of gut microbiome influence on metabolic disease in HIV and high-risk populations

2021 ◽  
Author(s):  
Abigail J.S. Armstrong ◽  
Kevin Quinn ◽  
Jennifer Fouquier ◽  
Sam X. Li ◽  
Jennifer M. Schneider ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
High Risk ◽  
Bacterial Translocation ◽  
Gut Microbiome ◽  
Metabolic Health ◽  
Hiv Positive ◽  
People Living With Hiv ◽  
Gut Microbes ◽  
Microbiome Composition ◽  
Living With Hiv

AbstractPoor metabolic health, characterized by insulin resistance and dyslipidemia, is higher in people living with HIV and has been linked with inflammation, anti-retroviral therapy (ART) drugs, and ART-associated lipodystrophy (LD). Metabolic disease is associated with gut microbiome composition outside the context of HIV but has not been deeply explored in HIV infection nor in high-risk men who have sex with men (HR-MSM), who have a highly altered gut microbiome composition. Furthermore, the contribution of increased bacterial translocation and associated systemic inflammation that has been described in HIV-positive and HR-MSM individuals has not been explored. We used a multi-omic approach to explore relationships between impaired metabolic health, defined using fasting blood markers, gut microbes, immune phenotypes and diet. Our cohort included ART-treated HIV positive MSM with and without LD, untreated HIV positive MSM, and HR-MSM. For HIV positive MSM on ART, we further explored associations with the plasma metabolome. We found that elevated plasma lipopolysaccharide binding protein (LBP) was the most important predictor of impaired metabolic health and network analysis showed that LBP formed a hub joining correlated microbial and immune predictors of metabolic disease. Taken together, our results suggest the role of inflammatory processes linked with bacterial translocation and interaction with the gut microbiome in metabolic disease among HIV positive and negative MSM.Importance StatementThe gut microbiome in people living with HIV (PLWH) is of interest as chronic infection often results in long term comorbidities. Metabolic disease is prevalent in PLWH even in well-controlled infection and has been linked with the gut microbiome in previous studies, but little attention has been given to PLWH. Furthermore, integrated analyses that consider gut microbiome together with diet, systemic immune activation, metabolites, and demographics have been lacking. In a systems-level analysis of predictors of metabolic disease in PLWH and men who are at high risk of acquiring HIV, we found that increased LBP, an inflammatory marker indicative of compromised intestinal barrier function, was associated with worse metabolic health. We also found impaired metabolic health associated with specific dietary components, gut microbes, and host and microbial metabolites. This work lays the framework for mechanistic studies aimed at targeting the microbiome to prevent or treat metabolic endotoxemia in HIV-infected individuals.

scholarly journals Role of Statins in the Primary Prevention of Atherosclerotic Cardiovascular Disease and Mortality in the Population with Mean Cholesterol in the Near-Optimal to Borderline High Range: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Bishnu M. Singh ◽  
Hari K. Lamichhane ◽  
Sanjay S. Srivatsa ◽  
Prabhat Adhikari ◽  
Bikash J. Kshetri ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Adverse Events ◽  
Statin Therapy ◽  
Meta Analysis ◽  
Density Lipoprotein ◽  
Cochrane Library ◽  
Atherosclerotic Cardiovascular Disease ◽  
Serious Adverse Events ◽  
Increased Risk ◽  
High Range

AbstractObjectiveThe objective of this meta-analysis was to analyze the benefits and harms of treating the population with statins in those having mean low-density lipoprotein cholesterol (LDL-C) in the near-optimal (100 to 129 mg/dl) to borderline high (130 to 159 mg/dl) range and free of cardiovascular disease (CVD). Methods: We searched PubMed, PubMed Central, Cochrane Library, and Google Scholar databases for randomized controlled trials (RCTs) published between 1994 and July 2020. We included RCTs with greater than 90% of participants free of CVD. Two reviewers independently screened the articles using the Covidence software, assessed the methodological quality using the risk of bias 2 tool, and analyzed the data using the RevMan 5.4 software. Results: Eleven trials were included. Statin therapy was associated with a decreased risk of myocardial infarction (RR=0.56, 95% CI: 0.47 to 0.67), major cerebrovascular events (RR=0.78, 95% CI: 0.63 to 0.96), major coronary events (RR=0.67, 95% CI: 0.57 to 0.80), composite cardiovascular outcome (RR=0.71, 95% CI: 0.62 to 0.82), revascularizations (RR=0.65, 95% CI: 0.57 to 0.74), angina (RR=0.76, 95% CI: 0.63 to 0.92) and hospitalization for cardiovascular causes (RR=0.74, 95% CI: 0.64 to 0.86). There was no benefit associated with statin therapy for cardiovascular mortality and coronary heart disease mortality. All-cause mortality benefit with statin therapy was seen in the population with diabetes and increased risk of CVD. Statin therapy was associated with no significant increased risk of myalgia, creatine kinase elevation, rhabdomyolysis, myopathy, incidence of any cancer, incidence of diabetes, withdrawal of the drug due to adverse events, serious adverse events, fatal cancer, and liver enzyme abnormalities. Conclusion: Statin therapy was associated with a reduced risk of cardiovascular disease and procedures without increased risk of harm in populations with mean LDL-C near-optimal to the borderline high range without prior atherosclerotic cardiovascular disease.

scholarly journals Statin Use for Atherosclerotic Cardiovascular Disease Prevention Among Sexual Minority Adults

2020 ◽  
Vol 9 (24) ◽  
Author(s):  
Yi Guo ◽  
Christopher W. Wheldon ◽  
Hui Shao ◽  
Carl J. Pepine ◽  
Eileen M. Handberg ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Sexual Orientation ◽  
Primary Prevention ◽  
Disease Prevention ◽  
Sexual Minority ◽  
Online Survey ◽  
Cardiovascular Disease Prevention ◽  
Atherosclerotic Cardiovascular Disease ◽  
Increased Risk ◽  
Statin Use

Background Sexual minority, or lesbian, gay, and bisexual (LGB), individuals are at increased risk for cardiovascular disease attributable to elevated rates of health risk factors. However, although there is clear evidence that statin use can prevent cardiovscular disease in certain adult populations, no studies have examined how statins are being used among the LGB population. This study aimed to examine the prevalence and predictors of statin use among LGB and non‐LGB individuals using Facebook‐delivered online surveys. Methods and Results We conducted a cross‐sectional online survey about statin use in adults ≥40 years of age between September and December 2019 using Facebook advertising (n=1531). We calculated the prevalence of statin use by age, sexual orientation, and statin benefit populations. We used multivariable logistic regression to examine whether statin use differed by sexual orientation, adjusting for covariates. We observed a significantly lower rate of statin use in the LGB versus non‐LGB respondents (20.8% versus 43.8%; P <0.001) in the primary prevention population. However, the prevalence of statin use was not statistically different in the LGB versus non‐LGB respondents in the secondary prevention population. Adjusting for the covariates, the LGB participants were less likely to use statins than the non‐LGB respondents in the primary prevention population (odds ratio, 0.37; 95% CI, 0.19–0.70). Conclusions Our results are the first to emphasize the urgent need for tailored, evidence‐based cardiovascular disease prevention programs that aim to promote statin use, and thus healthy aging, in the LGB population.

scholarly journals Efficacy and Safety of Vorapaxar by Intensity of Background Lipid‐Lowering Therapy in Patients With Peripheral Artery Disease: Insights From the TRA2P‐TIMI 50 Trial

2021 ◽  
Author(s):  
Ian C. Gilchrist ◽  
David A. Morrow ◽  
Mark A. Creager ◽  
Jeffrey W. Olin ◽  
Benjamin M. Scirica ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Peripheral Artery Disease ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Peripheral Artery ◽  
Thrombotic Risk ◽  
Increased Risk ◽  
Artery Disease ◽  
Ischemic Events ◽  
Statin Use

Background Patients with peripheral artery disease are at increased risk of both major adverse cardiovascular events (MACEs) and limb events. The pathobiology of limb events is likely multifactorial. Observational studies suggest a benefit of statin therapy for reducing the risk of limb ischemic events while randomized trials demonstrate a benefit with more potent antithrombotic therapies, particularly those targeting thrombin. Whether the effects of these therapeutic pathways are independent and complementary is not known. Methods and Results The TRA 2°P‐TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events–Thrombolysis in Myocardial Infarction 50) trial demonstrated that vorapaxar significantly reduced MACEs and limb events. The purpose of the current analysis was to evaluate the association of statin use and intensity and the occurrence of MACEs and limb events in 5845 patients with symptomatic peripheral artery disease randomized in TRA 2°P‐TIMI 50 and then to understand whether statin use modified the benefits of vorapaxar for MACEs or limb ischemic events. We found that statin therapy was associated with significantly lower risk of MACEs (hazard ratio [HR], 0.77; 95% CI, 0.66–0.89; P <0.001) and limb ischemic events (HR, 0.73; 95% CI, 0.60–0.89; P =0.002). The benefit of vorapaxar for reducing MACEs and limb events was consistent regardless of background statin ( P ‐interaction=0.715 and 0.073, respectively). Event rates were lowest in patients receiving the combination of statin therapy and vorapaxar. Conclusions In conclusion, statin use and intensity is associated with significantly lower rates of MACEs and limb ischemic events. Thrombin inhibition with vorapaxar is effective regardless of background statin therapy. These results suggest that targeting both lipid and thrombotic risk in peripheral artery disease is necessary in order to optimize outcomes.

scholarly journals Functional Deficits in Gut Microbiome of Young and Middle-Aged Adults with Prediabetes Apparent in Metabolizing Bioactive (Poly)phenols

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3595
Author(s):  
Xuhuiqun Zhang ◽  
Anqi Zhao ◽  
Amandeep K. Sandhu ◽  
Indika Edirisinghe ◽  
Britt M. Burton-Freeman
Keyword(s):  
Functional Capacity ◽  
Gut Microbiome ◽  
Reference Group ◽  
Biological Effects ◽  
Disease Status ◽  
Metabolic Health ◽  
Bioactive Metabolites ◽  
Microbiome Composition ◽  
Middle Aged Adults ◽  
Dietary Strategies

Background: Gut microbiota metabolize select dietary (poly)phenols to absorbable metabolites that exert biological effects important in metabolic health. Microbiota composition associated with health/disease status may affect its functional capacity to yield bioactive metabolites from dietary sources. Therefore, this study assessed gut microbiome composition and its related functional capacity to metabolize fruit (poly)phenols in individuals with prediabetes and insulin resistance (PreDM-IR, n = 26) compared to a metabolically healthy Reference group (n = 10). Methods: Shotgun sequencing was used to characterize gut microbiome composition. Targeted quantitative metabolomic analyses of plasma and urine collected over 24 h were used to assess microbial-derived metabolites in response to a (poly)phenol-rich raspberry test drink. Results: PreDM-IR compared to the Reference group: (1) enriched Blautia obeum and Blautia wexlerae and depleted Bacteroides dorei and Coprococcus eutactus. Akkermansia muciniphila and Bacteroides spp. were depleted in the lean PreDM-IR subset; and (2) impaired microbial catabolism of select (poly)phenols resulting in lower 3,8-dihydroxy-urolithin (urolithin A), phenyl-γ-valerolactones and various phenolic acids concentrations (p < 0.05). Controlling for obesity revealed relationships with microbial species that may serve as metagenomic markers of diabetes development and therapeutic targets. Conclusions: Data provide insight from multi-omics approaches to advance knowledge at the diet–gut–disease nexus serving as a platform for devising dietary strategies to improve metabolic health.

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