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The Gut Microbiota and Its Implication in the Development of Atherosclerosis and Related Cardiovascular Diseases.
Sanchez-Rodriguez, E, Egea-Zorrilla, A, Plaza-Díaz, J, Aragón-Vela, J, Muñoz-Quezada, S, Tercedor-Sánchez, L, Abadia-Molina, F
Nutrients. 2020;12(3)
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Cardiovascular disease (CVD) is the leading non-communicable disease and cause of death worldwide. The human microbiome can exert direct influences on bodily functions and in recent years much attention has been drawn to the significance of these microorganisms and their role in disease development. Divergences of microbiome patterns are also implicated in the progression and pathogenesis of CVD. This review describes the connection between host microbiota and CVD development. Elaborated are some of the potential mechanisms by which the microbiota and their associated metabolites can directly influence vascular tone and contribute to high blood pressure. More indirect processes, such as microbiota-mediated inflammation, insulin resistance and obesity are also accounted for. Furthermore, the authors discuss modulation of the microbiome composition as potential target for therapeutic interventions. Known influences that alter the microbiome are diet patterns, specific compounds such as probiotics, fish oils and polyphenols, physical activity and novel technologies like faecal transplants. This review outlines the many ways in which the microbiome can contribute to the development of CVD. Summarised are key points to consider in clinical practice, when navigating CVD and its microbiome associated risks factors.
Abstract
The importance of gut microbiota in health and disease is being highlighted by numerous research groups worldwide. Atherosclerosis, the leading cause of heart disease and stroke, is responsible for about 50% of all cardiovascular deaths. Recently, gut dysbiosis has been identified as a remarkable factor to be considered in the pathogenesis of cardiovascular diseases (CVDs). In this review, we briefly discuss how external factors such as dietary and physical activity habits influence host-microbiota and atherogenesis, the potential mechanisms of the influence of gut microbiota in host blood pressure and the alterations in the prevalence of those bacterial genera affecting vascular tone and the development of hypertension. We will also be examining the microbiota as a therapeutic target in the prevention of CVDs and the beneficial mechanisms of probiotic administration related to cardiovascular risks. All these new insights might lead to novel analysis and CVD therapeutics based on the microbiota.
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Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer's disease markers in subjects with mild cognitive impairment.
Nagpal, R, Neth, BJ, Wang, S, Craft, S, Yadav, H
EBioMedicine. 2019;47:529-542
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The exact causes of Alzheimer's disease (AD) are unknown, but there is evidence that AD is related to chronic inflammation, and it is thought that the gut bacteria (microbiome) and their metabolites can directly or indirectly affect brain functions. Diet can affect both the gut microbiome and brain health, and a ketogenic diet has been proposed to modulate processes associated with AD and is also known to affect gut microbial balance. The aim of this randomized, double-blind, crossover, pilot trial was to evaluate whether and how a modified Mediterranean-ketogenic diet (MMKD) alters the gut microbiome composition and whether this is associated with biomarkers for AD. 17 participants completed the study, 11 with mild cognitive impairment (MCI, an early stage of AD), and 6 counterparts with normal cognitive function (CN). Participants were randomly assigned to either a MMKD or an American Heart Association Diet (AHAD) for 6-weeks, followed by a 6-week washout, and then a 6-week intervention with the other diet. At baseline, participants with MCI had a microbiome composition different to that of the CN controls, with that of the MCI participants being considered less beneficial and potentially more pro-inflammatory. This difference was associated with biomarkers of AD. There was no difference in levels of microbial metabolites at baseline. Several types of bacteria were affected by the MMKD and AHAD, as were levels of faecal bacterial metabolites (short chain fatty acids). In particular, on the MMKD there was an increase in the metabolite butyrate which possesses neuroprotective actions and improves brain health. The authors conclude that the MMKD has a beneficial effect on the gut microbiome and associated AD biomarkers.
Abstract
BACKGROUND Alzheimer's disease (AD) prevalence is increasing, but its etiology remains elusive. Gut microbes can contribute to AD pathology and may help identifying novel markers and therapies against AD. Herein, we examine how the gut microbiome differs in older adults with mild cognitive impairment compared to cognitively normal counterparts, and whether and how a modified Mediterranean-ketogenic diet (MMKD) alters the gut microbiome signature in association with cerebrospinal fluid (CSF) AD biomarkers. METHODS A randomized, double-blind, cross-over, single-center pilot study of MMKD versus American Heart Association Diet (AHAD) intervention is performed on 17 subjects (age: 64.6 ± 6.4 yr), of which 11 have mild cognitive impairment, while 6 are cognitively normal. Subjects undergo MMKD and AHAD intervention for 6-weeks separated by 6-weeks washout periods. Gut microbiome, fecal short-chain fatty acids (SCFAs), and markers of AD in CSF including amyloid β (Aβ)-40 and Aß-42, total tau, and phosphorylated tau-181 (tau-p181) are measured at before and after diet interventions. FINDINGS At baseline, subjects with normal vs. impaired cognition show no notable difference in microbiome diversity but several unique microbial signatures are detected in subjects with mild cognitive impairment. Proteobacteria correlate positively with Aβ-42: Aβ-40 while fecal propionate and butyrate correlates negatively with Aβ-42 in subjects with mild cognitive impairment. Several bacteria are differently affected by the two diets with distinct patterns between cognitively normal and impaired subjects. Notably, the abundance of Enterobacteriaceae, Akkermansia, Slackia, Christensenellaceae and Erysipelotriaceae increases while that of Bifidobacterium and Lachnobacterium reduces on MMKD, while AHAD increases Mollicutes. MMKD slightly reduces fecal lactate and acetate while increasing propionate and butyrate. Conversely, AHAD increases acetate and propionate while reducing butyrate. INTERPRETATION The data suggest that specific gut microbial signatures may depict the mild cognitive impairment and that the MMKD can modulate the gut microbiome and metabolites in association with improved AD biomarkers in CSF.
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Pilot Study of Novel Intermittent Fasting Effects on Metabolomic and Trimethylamine N-oxide Changes During 24-hour Water-Only Fasting in the FEELGOOD Trial.
Washburn, RL, Cox, JE, Muhlestein, JB, May, HT, Carlquist, JF, Le, VT, Anderson, JL, Horne, BD
Nutrients. 2019;11(2)
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Intermittent fasting – the practice of significantly cutting food intake on a number of days and eating normally on others – has been connected with numerous health benefits such as weight loss, reduced risk of heart disease and Type 2 diabetes, longer life span and improved quality of life. This randomised, cross over trial of 30 healthy individuals sought to evaluate the effects of fasting on Trimethylamine N-oxide (TMAO) levels, a substance produced in humans by intestinal bacteria and associated with heart disease in humans. 74 other metabolites were also measured. Subjects were randomised to a ‘fasting first’ group, with water-only intake for 24 hours, followed by 24 hours of eating freely, or an ‘eating first’ group, before crossing over. Measurements were made at baseline, at the end of the fasting day and at the end of the eating day. The authors found that TMAO levels decreased on the fasting day compared to the eating day. These levels returned to pre-fasting levels within 24 hours. 30 of the other 74 metabolic markers, including some amino acids and fatty acids, achieved significant changes between fasting and eating days. The authors suggest that consistent and repeated episodes of intermittent fasting may lead to improved health and reduced risk of heart disease and diabetes. Nutrition Practitioners may wish to consider intermittent fasting when working with clients with these conditions.
Abstract
Intermittent fasting (IF) has been connected with health benefits such as weight loss, lower risk of coronary artery disease (CAD) and diabetes, increased longevity, and improved quality of life. However, the mechanisms of these IF benefits in humans require further investigation. This study sought to elucidate some of these mechanisms through secondary analyses of the Fasting and ExprEssion of Longevity Genes during fOOD abstinence (FEELGOOD) trial, in which apparently healthy participants were randomized in a Latin square design to a 24-h water-only fast and a 24-h ad libitum fed day. Two pathways were investigated, with trimethylamine N-oxide (TMAO) levels measured due to their association with elevated risk of CAD, along with conductance of a broad panel of metabolic analytes. Measurements were made at baseline, at the end of the fasting day, and at the end of the fed day. A fasting mean of 14.3 ng in TMAO was found versus the baseline mean of 27.1 ng with p = 0.019, although TMAO levels returned to baseline on refeeding. Further, acute alterations in levels of proline, tyrosine, galactitol, and urea plasma levels were observed along with changes in 24 other metabolites during the fasting period. These acute changes reveal short-term mechanisms which, with consistent repeated episodes of IF, may lead to improved health and reduced risk of CAD and diabetes.
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Nutraceutical approach for the management of cardiovascular risk - a combination containing the probiotic Bifidobacterium longum BB536 and red yeast rice extract: results from a randomized, double-blind, placebo-controlled study.
Ruscica, M, Pavanello, C, Gandini, S, Macchi, C, Botta, M, Dall'Orto, D, Del Puppo, M, Bertolotti, M, Bosisio, R, Mombelli, G, et al
Nutrition journal. 2019;18(1):13
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Probiotics have been shown to reduce total cholesterol (TC) and low-density lipoprotein (LDL-C – often called ‘bad’ cholesterol) in people with moderately raised cholesterol levels. A specific strain of probiotic called Bifidobacterium longum BB536, may decrease TC and LDL-C by reducing the reabsorption of cholesterol from the intestine, and, combined with other natural supplements, may be useful to manage high cholesterol in people at low risk of heart disease. This study was conducted to evaluate the effect of a nutraceutical (Lactoflorene Colesterolo®), containing Bifidobacterium longum BB536 (1bn CFUs) combined with red yeast rice (RYR) extract (10 mg/day monacolin K), niacin (16mg) and coenzyme Q10 (20mg) on levels of cholesterol and fats in the blood. This was a 12-week randomised, parallel, double-blind, placebo-controlled study, in which 33 adults at low risk of heart disease were given either the Bifidobacterium combination, or a placebo. Treatment with the Bifidobacterium combination significantly reduced total cholesterol by 16.7%, LDL-C by 25.7%, non-HDL-C by 24% and apolipoprotein-B by 17%. Triglycerides, HDL-C, apolipoprotein AI, lipoprotein (a) and proprotein convertase subtilisin/kexin type 9 (PCSK9) were unchanged. Markers of cholesterol synthesis and absorption suggested that a reduction in the synthesis of cholesterol had occurred without increased absorption of cholesterol. No adverse effects were reported in the study and the compliance rate was high at 97%. The use of nutraceuticals in the prevention of cardiovascular disease, as well as in other areas related to chronic diseases like cancer, is currently expanding.
Abstract
BACKGROUND Probiotics incorporated into dairy products have been shown to reduce total (TC) and LDL cholesterolemia (LDL-C) in subjects with moderate hypercholesterolemia. More specifically, probiotics with high biliary salt hydrolase activity, e.g. Bifidobacterium longum BB536, may decrease TC and LDL-C by lowering intestinal cholesterol reabsorption and, combined with other nutraceuticals, may be useful to manage hypercholesterolemia in subjects with low cardiovascular (CV) risk. This study was conducted to evaluate the efficacy and safety of a nutraceutical combination containing Bifidobacterium longum BB536, red yeast rice (RYR) extract (10 mg/day monacolin K), niacin, coenzyme Q10 (Lactoflorene Colesterolo®). The end-points were changes of lipid CV risk markers (LDL-C, TC, non-HDL-cholesterol (HDL-C), triglycerides (TG), apolipoprotein B (ApoB), HDL-C, apolipoprotein AI (ApoAI), lipoprotein(a) (Lp(a), proprotein convertase subtilisin/kexin type 9 (PCSK9)), and of markers of cholesterol synthesis/absorption. METHODS A 12-week randomized, parallel, double-blind, placebo-controlled study. Thirty-three subjects (18-70 years) in primary CV prevention and low CV risk (SCORE 0-1% in 24 and 2-4% in 9 subjects; LDL-C: 130-200 mg/dL) were randomly allocated to either nutraceutical (N = 16) or placebo (N = 17). RESULTS Twelve-week treatment with the nutraceutical combination, compared to placebo, significantly reduced TC (- 16.7%), LDL-C (- 25.7%), non-HDL-C (- 24%) (all p < 0.0001), apoB (- 17%, p = 0.003). TG, HDL-C, apoAI, Lp(a), PCSK9 were unchanged. Lathosterol:TC ratio was significantly reduced by the nutraceutical combination, while campesterol:TC ratio and sitosterol:TC ratio did not change, suggesting reduction of synthesis without increased absorption of cholesterol. No adverse effects and a 97% compliance were observed. CONCLUSIONS A 12-week treatment with a nutraceutical combination containing the probiotic Bifidobacterium longum BB536 and RYR extract significantly improved the atherogenic lipid profile and was well tolerated by low CV risk subjects. TRIAL REGISTRATION NCT02689934 .
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Role of whole grains versus fruits and vegetables in reducing subclinical inflammation and promoting gastrointestinal health in individuals affected by overweight and obesity: a randomized controlled trial.
Kopf, JC, Suhr, MJ, Clarke, J, Eyun, SI, Riethoven, JM, Ramer-Tait, AE, Rose, DJ
Nutrition journal. 2018;17(1):72
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Poor diet is the leading risk factor for premature death and disability in the United States. Poor diets lead to metabolic syndrome and its associated diseases such as heart disease and diabetes. The purpose of this study was to determine the impact of increasing intake of wholegrains or fruit and vegetables against a typical Western diet on inflammatory makers and gut microbiota composition. The study was a randomized, parallel arm feeding trial which enrolled fifty-two participants. The subjects were randomized into three groups (control, wholegrains, and fruit and vegetables). Results indicate that the wholegrain and fruit and vegetable diets had significant positive impacts on inflammatory markers. Interestingly, while both treatment groups decreased inflammatory markers, each decreased a different biomarker. The treatments induced individualised changes in microbiota composition such that treatment group differences were not identified. Authors conclude that wholegrain and fruit and vegetable diets have a positive impact on metabolic health in individuals affected by overweight or obesity.
Abstract
BACKGROUND Whole grains (WG) and fruits and vegetables (FV) have been shown to reduce the risk of metabolic disease, possibly via modulation of the gut microbiota. The purpose of this study was to determine the impact of increasing intake of either WG or FV on inflammatory markers and gut microbiota composition. METHODS A randomized parallel arm feeding trial was completed on forty-nine subjects with overweight or obesity and low intakes of FV and WG. Individuals were randomized into three groups (3 servings/d provided): WG, FV, and a control (refined grains). Stool and blood samples were collected at the beginning of the study and after 6 weeks. Inflammatory markers [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP), and high sensitivity C-reactive protein (hs-CRP)] were measured. Stool sample analysis included short/branched chain fatty acids (S/BCFA) and microbiota composition. RESULTS There was a significant decrease in LBP for participants on the WG (- 0.2 μg/mL, p = 0.02) and FV (- 0.2 μg/mL, p = 0.005) diets, with no change in those on the control diet (0.1 μg/mL, p = 0.08). The FV diet induced a significant change in IL-6 (- 1.5 pg/mL, p = 0.006), but no significant change was observed for the other treatments (control, - 0.009 pg/mL, p = 0.99; WG, - 0.29, p = 0.68). The WG diet resulted in a significant decrease in TNF-α (- 3.7 pg/mL; p < 0.001), whereas no significant effects were found for those on the other diets (control, - 0.6 pg/mL, p = 0.6; FV, - 1.4 pg/mL, p = 0.2). The treatments induced individualized changes in microbiota composition such that treatment group differences were not identified, except for a significant increase in α-diversity in the FV group. The proportions of Clostridiales (Firmicutes phylum) at baseline were correlated with the magnitude of change in LBP during the study. CONCLUSIONS These data demonstrate that WG and FV intake can have positive effects on metabolic health; however, different markers of inflammation were reduced on each diet suggesting that the anti-inflammatory effects were facilitated via different mechanisms. The anti-inflammatory effects were not related to changes in gut microbiota composition during the intervention, but were correlated with microbiota composition at baseline. TRIAL REGISTRATION ClinicalTrials.gov , NCT02602496 , Nov 4, 2017.
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Association between plant-based diets and plasma lipids: a systematic review and meta-analysis.
Yokoyama, Y, Levin, SM, Barnard, ND
Nutrition reviews. 2017;75(9):683-698
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Plasma lipids play a prominent role in heart disease and modifiable factors such as diet and lifestyle can facilitate in preventing or developing hyperlipidemia. Previous research has suggested that vegetarian diets are associated with lower plasma lipid concentrations, however long-term impacts of consuming a plant-based diet (PBD) has not been studied. The aim of this research was to conduct a systematic review and meta-analysis for studies that have examined the relationship between PBDs and plasma lipids. Thirty observational studies and 19 clinical trials were included in this analysis and showed consumption of a PBD was significantly associated with lower total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), but not in triglyceride concentrations. Based on these results, the authors conclude PBDs could offer individuals and healthcare professionals an effective option for reducing heart disease. They also add that while dietary changes may not be as powerful as pharmaceutical drugs in reducing plasma lipids, dietary and pharmacologic interventions can work together.
Abstract
CONTEXT Although a recent meta-analysis of randomized controlled trials showed that adoption of a vegetarian diet reduces plasma lipids, the association between vegetarian diets and long-term effects on plasma lipids has not been subjected to meta-analysis. OBJECTIVE The aim was to conduct a systematic review and meta-analysis of observational studies and clinical trials that have examined associations between plant-based diets and plasma lipids. DATA SOURCES MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for articles published in English until June 2015. STUDY SELECTION The literature was searched for controlled trials and observational studies that investigated the effects of at least 4 weeks of a vegetarian diet on plasma lipids. DATA EXTRACTION Two reviewers independently extracted the study methodology and sample size, the baseline characteristics of the study population, and the concentrations and variance measures of plasma lipids. Mean differences in concentrations of plasma lipids between vegetarian and comparison diet groups were calculated. Data were pooled using a random-effects model. RESULTS Of the 8385 studies identified, 30 observational studies and 19 clinical trials met the inclusion criteria (N = 1484; mean age, 48.6 years). Consumption of vegetarian diets was associated with lower mean concentrations of total cholesterol (-29.2 and -12.5 mg/dL, P < 0.001), low-density lipoprotein cholesterol (-22.9 and -12.2 mg/dL, P < 0.001), and high-density lipoprotein cholesterol (-3.6 and -3.4 mg/dL, P < 0.001), compared with consumption of omnivorous diets in observational studies and clinical trials, respectively. Triglyceride differences were -6.5 (P = 0.092) in observational studies and 5.8 mg/dL (P = 0.090) in intervention trials. CONCLUSIONS Plant-based diets are associated with decreased total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, but not with decreased triglycerides. SYSTEMATIC REVIEW REGISTRATION PROSPERO number CRD42015023783. Available at: https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015023783.