Age-related vascular endothelial dysfunction is a major antecedent to cardiovascular diseases. We investigated whether increased circulating levels of the gut microbiome-generated metabolite ...trimethylamine-N-oxide induces endothelial dysfunction with aging. In healthy humans, plasma trimethylamine-N-oxide was higher in middle-aged/older (64±7 years) versus young (22±2 years) adults (6.5±0.7 versus 1.6±0.2 µmol/L) and inversely related to brachial artery flow-mediated dilation (r=0.29, P<0.00001). In young mice, 6 months of dietary supplementation with trimethylamine-N-oxide induced an aging-like impairment in carotid artery endothelium-dependent dilation to acetylcholine versus control feeding (peak dilation79±3% versus 95±3%, P<0.01). This impairment was accompanied by increased vascular nitrotyrosine, a marker of oxidative stress, and reversed by the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl. Trimethylamine-N-oxide supplementation also reduced activation of endothelial nitric oxide synthase and impaired nitric oxide-mediated dilation, as assessed with the nitric oxide synthase inhibitor L-NAME (N-nitro-L-arginine methyl ester). Acute incubation of carotid arteries with trimethylamine-N-oxide recapitulated these events. Next, treatment with 3,3-dimethyl-1-butanol for 8 to 10 weeks to suppress trimethylamine-N-oxide selectively improved endothelium-dependent dilation in old mice to young levels (peak90±2%) by normalizing vascular superoxide production, restoring nitric oxide-mediated dilation, and ameliorating superoxide-related suppression of endothelium-dependent dilation. Lastly, among healthy middle-aged/older adults, higher plasma trimethylamine-N-oxide was associated with greater nitrotyrosine abundance in biopsied endothelial cells, and infusion of the antioxidant ascorbic acid restored flow-mediated dilation to young levels, indicating tonic oxidative stress-related suppression of endothelial function with higher circulating trimethylamine-N-oxide. Using multiple experimental approaches in mice and humans, we demonstrate a clear role of trimethylamine-N-oxide in promoting age-related endothelial dysfunction via oxidative stress, which may have implications for prevention of cardiovascular diseases.
PURPOSEThe objective of this systematic review of literature was to evaluate and summarize published research that has investigated the association between exercise and gut microbial composition in ...mammals.
METHODSThis review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The databases searched for this review includedPubMed; PubMed Central; Medline; Cumulative Index of Nursing and Allied Health Literature; Web of Science; Commonwealth Agricultural Bureaux Direct; Health SourceNursing Academic Edition; Clinicaltrials.gov; International Prospective Register of Systematic Reviews (PROSPERO); and the Cochrane Library.
RESULTSTwenty-five articles met the inclusion criteria17 rodent, one canine, two equine, and five human studies. All studies in rodents and equines included control groups; whereas only one study in humans included a control group. The remaining were cross-sectional or cohort studies. All studies in rodents controlled for dietary intake and one study in humans implemented a 3-d dietary control. Eleven studies assessed voluntary exercise and 13 studies used forced exercise. Diversification within the Firmicutes phylum was consistently observed in exercise groups across studies. There were no consistent trends within Bacteroidetes, Actinobacteria, or Proteobacteria phyla. In general, the potential interactions between exercise and diet composition and their respective influences on the intestinal microbiome were not well characterized.
CONCLUSIONSExercise was associated with changes in gut microbial composition, an increase in butyrate producing bacteria and an increase in fecal butyrate concentrations independent of diet in rodents and humans. The overall quality of evidence in the studies in humans was low and the risk of bias was unclear. Future studies with standardized reporting and rigorous dietary control in larger samples are needed to further determine the influence of exercise on gut microbial composition.
Grape pomace (GP) management has been a challenge worldwide. We have previously demonstrated a biorefinery process to recover oil and polyphenols, and produce biofuels from GP sequentially, although ...over 50% of GP solid waste remains post-processing. To approach zero solid waste during GP processing, herein a pyrolysis process was designed for converting GP and its secondary processing wastes to biochars, which were then evaluated for lead (Pb) adsorption from water. GP lignin pyrolyzed at 700 °C (GPL2700 biochar) with specific surface area of 485 m2/g showed the highest Pb adsorption capacity, and achieved 66.5% of Pb removal from an initially high concentration of 300 mg/L within 30 min. At low initial Pb concentrations (50–3000 μg/L), GPL2700 biochar could reduce Pb concentrations to 0.208–77.2 μg/L. In addition, experimental and modeling results revealed that both physisorption and chemisorption mechanisms were involved in the adsorption process of GPL2700 biochar.
•Grape pomace (GP) and its secondary waste were used for biochar production.•GP lignin derived biochar (GPL2700) showed the highest Pb adsorption capacity.•GPL2700 showed good adsorption at a low Pb level in contaminated drinking water.•Chemisorption and physisorption mechanisms accounted for Pb removal of GPL2700.
The goal of this project was to increase the nutrient value of fillets, by-product muscle, and offal of aquacultured tilapia. A diet that includes seafood with a high omega-3 (n-3) fatty acid ...content, more specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to have numerous health benefits for consumers. Improved nutrient value of the offal may also attract new market opportunities for the aquaculture industry. Tilapia were cultured on different experimental feeds that contained various levels of n-3 fatty acids from either fish oil (FO) or algae meal (AM) that were used to replace corn oil. The experimental diets included a control (corn oil 6.3%), FO1%, FO3%, FO5%, AM1.75%, AM5.26%, and AM8.77%. All diets were formulated to be isocaloric, isonitrogenous, and isolipid. Three hundred and fifty tilapia with an initial mean weight of 158±2 g were cultured in a recirculating aquaculture system (seven diets replicated at the tank level, 14 tanks, 25 fish per tank). For all of the production performance data, no differences (P>0.05) were observed between the experimental groups which included survival (overall mean ± standard error, 99.4±0.3%), growth per week (45.4±1.0 g/wk), food conversion ratio (1.32±0.03), fillet yield (44.4±0.2%), hepatosomatic index (1.61±0.02), viscerosomatic index (2.86±0.06), and mesenteric fat index (0.97±0.04). Fillet and rib meat tissues were collected at weeks four and eight, and liver and mesenteric fat tissues were collected at week eight. Fatty acids were extracted, methylated and identified with gas chromatography-mass spectrometry. All tissues had improved fatty acid profiles (higher n-3, lower n-6, n-6:n-3) with increasing levels of FO and AM in the diet. For example, the best diet for significantly (P<0.05) improving the lipid profile in tilapia fillets at week eight was diet AM8.77%. In the fillet, total n-3 was increased (control versus AM8.77%) from 151.2±19.0 to 438.7±14.2 mg per 4 ounce (113 g) serving and n-6:n-3 ratio was improved from 5.19±0.76 to 1.29±0.03.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Key points
Age‐related arterial dysfunction, characterized by oxidative stress‐ and inflammation‐mediated endothelial dysfunction and arterial stiffening, is the primary risk factor for ...cardiovascular diseases.
To investigate whether age‐related changes in the gut microbiome may mediate arterial dysfunction, we suppressed gut microbiota in young and old mice with a cocktail of broad‐spectrum, poorly‐absorbed antibiotics in drinking water for 3–4 weeks.
In old mice, antibiotic treatment reversed endothelial dysfunction and arterial stiffening and attenuated vascular oxidative stress and inflammation.
To provide insight into age‐related changes in gut microbiota that may underlie these observations, we show that ageing altered the abundance of microbial taxa associated with gut dysbiosis and increased plasma levels of the adverse gut‐derived metabolite trimethylamine N‐oxide.
The results of the present study provide the first proof‐of‐concept evidence that the gut microbiome is an important mediator of age‐related arterial dysfunction and therefore may be a promising therapeutic target for preserving arterial function with ageing, thereby reducing the risk of cardiovascular diseases.
Oxidative stress‐mediated arterial dysfunction (e.g. endothelial dysfunction and large elastic artery stiffening) is the primary mechanism driving age‐related cardiovascular diseases. Accumulating evidence suggests the gut microbiome modulates host physiology because dysregulation (‘gut dysbiosis’) has systemic consequences, including promotion of oxidative stress. The present study aimed to determine whether the gut microbiome modulates arterial function with ageing. We measured arterial function in young and older mice after 3–4 weeks of treatment with broad‐spectrum, poorly‐absorbed antibiotics to suppress the gut microbiome. To identify potential mechanistic links between the gut microbiome and age‐related arterial dysfunction, we sequenced microbiota from young and older mice and measured plasma levels of the adverse gut‐derived metabolite trimethylamine N‐oxide (TMAO). In old mice, antibiotics reversed endothelial dysfunction area‐under‐the‐curve carotid artery dilatation to acetylcholine in young: 345 ± 16 AU vs. old control (OC): 220 ± 34 AU, P < 0.01; vs. old antibiotic‐treated (OA): 334 ± 15 AU; P < 0.01 vs. OC and arterial stiffening (aortic pulse wave velocity in young: 3.62 ± 0.15 m s−1 vs. OC: 4.43 ± 0.38 m s−1; vs. OA: 3.52 ± 0.35 m s−1; P = 0.03). These improvements were accompanied by lower oxidative stress and greater antioxidant enzyme expression. Ageing altered the abundance of gut microbial taxa associated with gut dysbiosis. Lastly, plasma TMAO was higher with ageing (young: 2.6 ± 0.4 μmol L−1 vs. OC: 7.2 ± 2.0 μmol L−1; P < 0.0001) and suppressed by antibiotic treatment (OA: 1.2 ± 0.2 μmol L−1; P < 0.0001 vs. OC). The results of the present study provide the first evidence for the gut microbiome being an important mediator of age‐related arterial dysfunction and oxidative stress and suggest that therapeutic strategies targeting gut microbiome health may hold promise for preserving arterial function and reducing cardiovascular risk with ageing in humans.
Key points
Age‐related arterial dysfunction, characterized by oxidative stress‐ and inflammation‐mediated endothelial dysfunction and arterial stiffening, is the primary risk factor for cardiovascular diseases.
To investigate whether age‐related changes in the gut microbiome may mediate arterial dysfunction, we suppressed gut microbiota in young and old mice with a cocktail of broad‐spectrum, poorly‐absorbed antibiotics in drinking water for 3–4 weeks.
In old mice, antibiotic treatment reversed endothelial dysfunction and arterial stiffening and attenuated vascular oxidative stress and inflammation.
To provide insight into age‐related changes in gut microbiota that may underlie these observations, we show that ageing altered the abundance of microbial taxa associated with gut dysbiosis and increased plasma levels of the adverse gut‐derived metabolite trimethylamine N‐oxide.
The results of the present study provide the first proof‐of‐concept evidence that the gut microbiome is an important mediator of age‐related arterial dysfunction and therefore may be a promising therapeutic target for preserving arterial function with ageing, thereby reducing the risk of cardiovascular diseases.
Dietary administration of cocoa flavanols may be an effective complementary strategy for alleviation or prevention of metabolic syndrome, particularly glucose intolerance. The complex flavanol ...composition of cocoa provides the ability to interact with a variety of molecules, thus allowing numerous opportunities to ameliorate metabolic diseases. These interactions likely occur primarily in the gastrointestinal tract, where native cocoa flavanol concentration is high. Flavanols may antagonize digestive enzymes and glucose transporters, causing a reduction in glucose excursion, which helps patients with metabolic disorders maintain glucose homeostasis. Unabsorbed flavanols, and ones that undergo enterohepatic recycling, will proceed to the colon where they can exert prebiotic effects on the gut microbiota. Interactions with the gut microbiota may improve gut barrier function, resulting in attenuated endotoxin absorption. Cocoa may also positively influence insulin signaling, possibly by relieving insulin-signaling pathways from oxidative stress and inflammation and/or via a heightened incretin response. The purpose of this review is to explore the mechanisms that underlie these outcomes, critically review the current body of literature related to those mechanisms, explore the implications of these mechanisms for therapeutic utility, and identify emerging or needed areas of research that could advance our understanding of the mechanisms of action and therapeutic potential of cocoa flavanols.
Age-related cognitive changes can be the first indication of the progression to dementias, such as Alzheimer's disease. These changes may be driven by a complex interaction of factors including diet, ...activity levels, genetics, and environment. Here we review the evidence supporting relationships between flavonoids, physical activity, and brain function. Recent
experiments and human clinical trials have shown that flavonoid-rich foods can inhibit neuroinflammation and enhance cognitive performance. Improved cognition has also been correlated with a physically active lifestyle, and with the functionality and diversity of the gut microbiome. The great majority (+ 90%) of dietary flavonoids are biotransformed into phytoactive phenolic metabolites at the gut microbiome level prior to absorption, and these prebiotic flavonoids modulate microbiota profiles and diversity. Health-relevant outcomes from flavonoid ingestion may
be realized in the presence of a robust microbiome. Moderate-to-vigorous physical activity (MVPA) accelerates the catabolism and uptake of these gut-derived anti-inflammatory and immunomodulatory metabolites into circulation. The gut microbiome exerts a profound influence on cognitive function; moderate exercise and flavonoid intake influence cognitive benefits; and exercise and flavonoid intake influence the microbiome. We conclude that there is a potential for
impacts of flavonoid intake and physical exertion on cognitive function, as modulated by the gut microbiome, and that the combination of a flavonoid-rich diet and routine aerobic exercise may
cognitive benefits and reduce cognitive decline in an aging population, via mechanisms mediated by the gut microbiome. Mechanistic animal studies and human clinical interventions are needed to further explore this hypothesis.
Abstract The gut microbiota plays an obligatory role in the metabolism of nutrients containing trimethylamine moieties, such as l -carnitine and choline, leading to the production of the ...proatherogenic trimethylamine- N -oxide (TMAO). We hypothesized that a short-term, high-fat diet would increase fasting and postprandial plasma concentrations of TMAO in response to a high-fat meal challenge. Following a 2-week eucaloric control diet, 10 nonobese men (18-30 years) consumed a eucaloric, high-fat diet (55% fat) for 5 days. Plasma TMAO was measured after a 12-hour fast and each hour after for 4 hours following a high-fat meal (63% fat) at baseline and after the high-fat diet using ultraperformance liquid chromatography/ tandem mass spectrometry. Fasting plasma TMAO did not increase significantly following the high-fat diet (1.83 ± 0.21 vs 1.6 ± 0.24 μ mol/L). However, plasma TMAO was higher at hour 1 (2.15 ± 0.28 vs 1.7 ± 0.30 μ mol/L), hour 2 (2.3 ± 0.29 vs 1.8 ± 0.32 μ mol/L), hour 3 (2.4 ± 0.34 vs 1.58 ± 0.19 μ mol/L), and hour 4 (2.51 ± 0.33 vs 1.5 ± 0.12 μ mol/L) (all P < .05) following the high-fat diet as compared with the baseline postprandial response. In conclusion, a short-term, high-fat diet does not increase fasting plasma TMAO concentrations but appears to increase postprandial TMAO concentrations in healthy, nonobese, young men. Future studies are needed to determine the mechanisms responsible for these observations.
Scope
Loss of functional β‐cell mass is central for the deterioration of glycemic control in diabetes. The incretin hormone glucagon‐like peptide‐1 (GLP‐1) plays a critical role in maintaining ...glycemic homeostasis via potentiating glucose‐stimulated insulin secretion and promoting β‐cell mass. Agents that can directly promote GLP‐1 secretion, thereby increasing insulin secretion and preserving β‐cell mass, hold great potential for the treatment of T2D.
Methods and results
GluTag L‐cells, INS832/13 cells, and mouse ileum crypts and islets are cultured for examining the effects of flavone hispidulin on GLP‐1 and insulin secretion. Mouse livers and isolated hepatocytes are used for gluconeogenesis. Streptozotocin‐induced diabetic mice are treated with hispidulin (20 mg kg−1 day−1, oral gavage) for 6 weeks to evaluate its anti‐diabetic potential. Hispidulin stimulates GLP‐1 secretion from the L‐cell line, ileum crypts, and in vivo. This hispidulin action is mediated via activation of cyclic adenosine monophosphate/protein kinase A signaling. Hispidulin significantly improves glycemic control in diabetic mice, concomitant with improved insulin release, and β‐cell survival. Additionally, hispidulin decreases hepatic pyruvate carboxylase expression in diabetic mice and suppresses gluconeogenesis in hepatocytes. Furthermore, hispidulin stimulates insulin secretion from β‐cells.
Conclusion
These findings suggest that Hispidulin may be a novel dual‐action anti‐diabetic compound via stimulating GLP‐1 secretion and suppressing hepatic glucose production.
In this study, it is found for the first time that hispidulin, a naturally occurring flavone is an inhibitor of phosphodiesterase in intestinal L‐cells, which results in intracellular cAMP (cyclic adenosine monophosphate) accumulation and subsequent activation of protein kinase A, leading to increased GLP‐1 secretion. In addition, hispidulin suppresses gluconeogenesis in primary mouse hepatocytes. Oral administration of hispidulin significantly improves glycemic control in diabetic mice, concomitant with improved insulin release and cell survival.
Choline is metabolized by the gut microbiota into trimethylamine (TMA), the precursor of pro-atherosclerotic molecule trimethylamine N-oxide (TMAO). A reduction in TMA formation has shown ...cardioprotective effects, and some phytochemicals may reduce TMA formation. This study aimed to develop an optimized, high-throughput anaerobic fermentation methodology to study the inhibition of choline microbial metabolism into TMA by phenolic compounds with healthy human fecal starter. Optimal fermentation conditions were: 20% fecal slurry (1:10 in PBS), 100 µM choline, and 12 h fermentation. Additionally, 10 mM of 3,3-dimethyl-1-butanol (DMB) was defined as a positive TMA production inhibitor, achieving a ~50% reduction in TMA production. Gallic acid and chlorogenic acid reported higher TMA inhibitory potential (maximum of 80-90% TMA production inhibition), with IC
around 5 mM. Neither DMB nor gallic acid or chlorogenic acid reduced TMA production through cytotoxic effects, indicating mechanisms such as altered TMA-lyase activity or expression.
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