Characterization of Mucosal Dysbiosis of Early Colonic Neoplasia.

Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesions in the colon that can be detected by high-definition chromoendoscopy with contrast dye spray. Although frequently associated with synchronous adenomas, their role in colorectal tumor development, particularly in the proximal colon, is still not clear. The goal of this study was to evaluate the profile of colon-adherent bacteria associated with proximal ACF and to investigate their relationship to the presence and subtype of synchronous polyps present throughout the colon. Forty-five subjects undergoing a screening or surveillance colonoscopy were included in this retrospective study. Bacterial cells adherent to the epithelia of ACF and normal mucosal biopsies were visualized by in situ hybridization within confocal tissue sections. ACF showed significantly greater heterogeneity in their bacterial microbiome profiles compared with normal mucosa. One of the bacterial community structures we characterized was strongly correlated with the presence of synchronous polyps. Finally, using DNA mass spectrometry to evaluate a panel of colorectal cancer hotspot mutations present in the ACF, we found that three APC gene mutations were positively associated with the presence of Instestinibacter sp., whereas KRAS mutations were positively correlated with Ruminococcus gnavus. This result indicates a potential relationship between specific colon-associated bacterial species and somatically acquired CRC-related mutations. Overall, our findings suggest that perturbations to the normal adherent mucosal flora may constitute a risk factor for early neoplasia, demonstrating the potential impact of mucosal dysbiosis on the tissue microenvironment and behavior of ACF that may facilitate their progression towards more advanced forms of neoplasia.

Effects of Freeze-Dried Grape Powder on High-Density Lipoprotein Function in Adults with Metabolic Syndrome: A Randomized Controlled Pilot Study.

BACKGROUND: High-density lipoprotein (HDL) particles are protective against atherosclerosis. However, HDL function is impaired in metabolic syndrome (MetS) due to low-grade inflammation and dyslipidemia. Foods containing polyphenols, such as grapes, may prevent HDL dysfunction via antioxidant or anti-inflammatory effects. We evaluated the effects of grape powder ingestion on measures of HDL function in adults with MetS. METHODS: Twenty adults (age: 32-70 years; body mass index: 25.3-45.4 kg/m2) consumed either 60 grams/day of freeze-dried grape powder (GRAPE) or a placebo for 4 weeks, separated by a 3-week washout period, in a randomized, double-blind crossover study. The primary outcome was serum paraoxonase-1 (PON1) arylesterase activity, a measure of HDL antioxidant function. Secondary outcomes included PON1 lactonase activity, plasma lipids, metabolic markers, cholesterol efflux capacity, and other HDL functional markers. RESULTS: After 4 weeks, GRAPE did not alter the serum PON1 activity or other markers of HDL function compared with placebo. Measures of HDL function were positively correlated with each other and inversely with measures of insulin resistance and inflammation. GRAPE intake led to a significant reduction in fasting plasma triglycerides compared with placebo (P = 0.032). No other significant effects of GRAPE were observed for other plasma lipids, anthropometrics, or metabolic measures. CONCLUSIONS: Grape powder consumption did not impact HDL function in this cohort of adults with MetS. However, it was shown to improve fasting triglycerides, a risk factor for cardiovascular disease.

Effects of Egg Consumption and Choline Supplementation on Plasma Choline and Trimethylamine-N-Oxide in a Young Population.

Background: Plasma trimethylamine-N-oxide (TMAO) concentrations have been associated with cardiovascular disease risk. Eggs are a rich source of choline, which is a precursor of TMAO.Objective: The effects of egg intake versus daily choline supplementation were evaluated on plasma choline and TMAO in a young, healthy population.Methods: Thirty participants (14 males, 16 females; 25.6 ± 2.3 years; body mass index = 24.3 ± 2.9 kg/m2) were enrolled in this 13-week crossover intervention. After a 2-week washout, participants were randomized to consume either 3 eggs/d or a choline bitartrate supplement (∼ 400 mg choline total in eggs or supplement) for 4 weeks. Following a 3-week washout, participants were switched to the alternate treatment. Dietary records were measured at the end of each period. Plasma TMAO and choline were measured at baseline and at the end of each dietary intervention. Gene expression of scavenger receptors associated with plasma TMAO were quantified at the end of each intervention.Results: Compared to the choline supplement, intake of total fat, cholesterol, selenium, and vitamin E were higher (p < 0.05), whereas carbohydrate intake was lower (p < 0.001) with consumption of 3 eggs/d. Fasting plasma choline increased 20% (p = 0.023) with egg intake, while no changes were observed with choline supplementation. Plasma TMAO levels were not different between dietary treatments or compared to baseline.Conclusions: Dietary choline appears to be more bioavailable via egg consumption when compared to a choline supplement. Plasma TMAO concentrations were not affected in healthy participants after 4 weeks of taking ∼400 mg/d choline either via eggs or choline supplementation.

TA-65, A Telomerase Activator improves Cardiovascular Markers in Patients with Metabolic Syndrome.

BACKGROUND: Telomerase Activator 65 (TA-65), a compound extracted from Astragalus membranaceus has been used in Chinese traditional medicine for extending lifespan. Scarce information exists on the effects of TA-65 on parameters of metabolic syndrome (MetS). METHODS: We recruited 40 patients with MetS to determine the effects of TA-65 on dyslipidemias, hypertension, and oxidative stress in this at-risk population. The study was a double-blind, randomized crossover design in which patients were allocated to consume either 16 mg daily of a TA-65 supplement or a placebo for 12 weeks. Following a 3-week washout, participants were allocated to the alternate treatment for an additional 12 weeks. Anthropometric and biological markers were measured at the end of each treatment. Plasma lipids, glucose, CReactive Protein (CRP), liver enzymes, and glycosylated hemoglobin were measured using a Cobas c-111. Inflammatory cytokines were measured by Luminex technology and markers of oxidative stress by the use of spectroscopy. RESULTS: Compared to the placebo period, HDL cholesterol (HDL-C) was higher while body mass index, waist circumference, and the LDL/HDL ratio were lower (p < 0.05) during TA-65 treatment. In addition, plasma tumor necrosis factor-α (TNF-α) was lower during the TA-65 period (p < 0.05). Positive correlations were observed in changes between the placebo and the TA-65 periods in HDL-C and CRP (r = -0.511, p < 0.01), alanine aminotransferase (r = -0.61, p < 0.001) and TNF-α (r = -0.550, p < 0.001) suggesting that the favorable changes observed in HDL were associated with decreases in inflammation. CONCLUSION: TA-65 improved key markers of cardiovascular disease risk, which were also associated with reductions in inflammation.

Intake of 3 Eggs per Day When Compared to a Choline Bitartrate Supplement, Downregulates Cholesterol Synthesis without Changing the LDL/HDL Ratio.

Cardiovascular disease (CVD) risk is associated with high concentrations of low-density lipoprotein cholesterol (LDL-C). The impact of dietary cholesterol on plasma lipid concentrations still remains a concern. The effects of egg intake in comparison to choline bitartrate supplement was studied in a young, healthy population. Thirty participants were enrolled for a 13-week intervention. After a 2-week run-in period, subjects were randomized to consume either 3 eggs/day or a choline bitartrate supplement (~400 mg choline for both treatments) for 4-weeks each. After a 3-week washout period, they were allocated to the alternate treatment. Dietary records, plasma lipids, apolipoproteins (apo) concentrations, and peripheral blood mononuclear cell expression of regulatory genes for cholesterol homeostasis were assessed at the end of each intervention. Dietary intakes of saturated and monounsaturated fat were higher with the consumption of eggs compared to the choline period. In addition, higher plasma concentrations of total cholesterol (7.5%), high density lipoprotein cholesterol (HDL-C) (5%) and LDL-C (8.1%) were observed with egg consumption (p < 0.01), while no change was seen in LDL-C/HDL-C ratio, a key marker of heart disease risk. Compared to choline supplementation, intake of eggs resulted in higher concentrations of plasma apoA-I (8%) and apoE (17%) with no changes in apoB. Sterol regulatory element-binding protein 2 and 3-hydroxy-3-methylglutaryl-CoA reductase expression were lower with egg consumption by 18% and 31%, respectively (p < 0.05), suggesting a compensation to the increased dietary cholesterol load. Therefore, dietary cholesterol from eggs appears to regulate endogenous synthesis of cholesterol in such a way that the LDL-C/HDL-C ratio is maintained.

Compared to an Oatmeal Breakfast, Two Eggs/Day Increased Plasma Carotenoids and Choline without Increasing Trimethyl Amine N-Oxide Concentrations.

BACKGROUND: Habitual consumption of eggs has been hypothesized to positively modify biomarkers of cardiovascular disease risk through proposed antioxidant properties. OBJECTIVES: To examine this relationship, 50 young, healthy men and women were enrolled into a randomized crossover clinical intervention. METHODS: Participants consumed either 2 eggs per day or one packet of oatmeal a day for 4 weeks, followed by a 3-week wash-out and crossed over to the alternate breakfast. Fasting blood samples and peripheral blood mononuclear cells (PBMCs) were collected at the end of each intervention period. RESULTS: Increases in plasma large high-density lipoprotein (HDL) and large low-density lipoprotein (LDL) particle concentrations as measured by nuclear magnetic resonance were found following egg consumption (p < 0.001, p < 0.05), respectively, with increases in apolipoprotein concentration as well (p < 0.05). Though there was no difference in the intake of antioxidants lutein and zeaxanthin, a significant increase in plasma concentrations of these carotenoids was observed (p < 0.001) after egg consumption. There was no change in lecithin-cholesterol acyl transferase, cholesteryl ester transfer protein, or paroxanase-1 arylesterase activities between breakfast interventions. Dietary and plasma choline were both higher following egg consumption compared to oatmeal consumption (p < 0.001); however, there was no change in plasma trimethylamine N-oxide (TMAO) concentrations. Two eggs per day had no impact on PBMC gene expression related to cholesterol metabolism, oxidation, or TMAO production. CONCLUSIONS: These results suggest that compared to oatmeal, consumption of 2 eggs for breakfast provided increased plasma carotenoids and improved biomarkers of cardiovascular disease (CVD) risk while not affecting TMAO levels in this population.

Intake of up to 3 Eggs/Day Increases HDL Cholesterol and Plasma Choline While Plasma Trimethylamine-N-oxide is Unchanged in a Healthy Population.

Eggs are a source of cholesterol and choline and may impact plasma lipids and trimethylamine-N-oxide (TMAO) concentrations, which are biomarkers for cardiovascular disease (CVD) risk. Therefore, the effects of increasing egg intake (0, 1, 2, and 3 eggs/day) on these and other CVD risk biomarkers were evaluated in a young, healthy population. Thirty-eight subjects [19 men/19 women, 24.1 ± 2.2 years, body mass index (BMI) 24.3 ± 2.5 kg/m2] participated in this 14-week crossover intervention. Participants underwent a 2-week washout with no egg consumption, followed by intake of 1, 2, and 3 eggs/day for 4 weeks each. Anthropometric data, blood pressure (BP), dietary records, and plasma biomarkers (lipids, glucose, choline, and TMAO) were measured during each intervention phase. BMI, waist circumference, systolic BP, plasma glucose, and plasma triacylglycerol did not change throughout the intervention. Diastolic BP decreased with egg intake (P < 0.05). Compared to 0 eggs/day, intake of 1 egg/day increased HDL cholesterol (HDL-c) (P < 0.05), and decreased LDL cholesterol (LDL-c) (P < 0.05) and the LDL-c/HDL-c ratio (P < 0.01). With intake of 2-3 eggs/day, these changes were maintained. Plasma choline increased dose-dependently with egg intake (P < 0.0001) while fasting plasma TMAO was unchanged. These results indicate that in a healthy population, consuming up to 3 eggs/day results in an overall beneficial effect on biomarkers associated with CVD risk, as documented by increased HDL-c, a reduced LDL-c/HDL-c ratio, and increased plasma choline in combination with no change in plasma LDL-c or TMAO concentrations.