Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats

Diet‐induced obesity is associated to an imbalance in the normal gut microbiota composition. Resveratrol and quercetin, widely known for their health beneficial properties, have low bioavailability and, when reach the colon, they are targets of the gut microbial ecosystem. Hence, the use of these molecules in obesity might be considered as a potential strategy to modulate intestinal bacterial composition. The purpose of this study was to determine whether trans‐resveratrol and quercetin administration could counteract gut microbiota dysbiosis produced by high‐fat sucrose diet (HFS) and in turn, improve gut health. Wistar rats were randomized into four groups fed a HFS diet supplemented or not with trans‐resveratrol (15 mg/kg BW/day), quercetin (30 mg/kg BW/day) or a combination of both polyphenols at those doses. Administration of both polyphenols together prevented body‐weight gain and reduced serum insulin levels. Moreover, individual supplementation of trans‐resveratrol and quercetin effectively reduced serum insulin levels and insulin resistance. Quercetin supplementation generated a great impact on gut microbiota composition at different taxonomic levels, attenuating Firmicutes/Bacteroidetes ratio and inhibiting the growth of bacterial species previously associated to diet‐induced obesity (Erysipelotrichaceae, Bacillus, Eubacterium 1 cylindroides). Overall, the administration of quercetin was found to be effective in lessening HFS diet‐induced gut microbiota dysbiosis. In contrast, trans‐resveratrol supplementation alone or in combination with quercetin, scarcely modified the profile of gut bacteria, but acted at intestinal level altering the mRNA expression of tight‐junction proteins (TJPs) and inflammation associated genes

Shifts in microbiota species and fermentation products in a dietary model enriched in fat and sucrose

The gastrointestinal tract harbours a “superorganism” called the gut microbiota, which is known to play a crucial role in the onset and development of diverse diseases. This internal ecosystem, far from being a static environment, could be willingly manipulated by diet and dietary components. Feeding animals with high-fat sucrose diets entails diet-induced obesity, a model which is usually used in research to mimic the obese phenotype of Western societies. The aim of the present study was to identify gut microbiota dysbiosis and associated metabolic changes produced in 5 male Wistar rats fed a high-fat sucrose (HFS) diet for six weeks and to compare it with the basal microbial composition. For this purpose, DNA extracted from faeces at baseline and after the treatment was analysed by amplification of the V4-V6 region of the 16S ribosomal DNA (rDNA) gene using 454 pyrosequencing. Short-chain fatty acids (SCFA), acetate, propionate and butyrate, were also evaluated by gas chromatography-mass spectrometry (GC-MS). At the end of the treatment, gut microbiota composition significantly differed at phylum level (Firmicutes, Bacteroidetes and Proteobacteria) and class level (Erisypelotrichi, Deltaproteobacteria, Bacteroidia and Bacilli). Interestingly, Clostridia class showed a significant decrease after the HFS-diet treatment, which correlated with visceral adipose tissue, and is likely mediated by dietary carbohydrates. Of particular interest, Clostridium cluster XIVa species were significantly reduced and changes were identified in the relative abundance of other specific bacterial species (Mitsuokella jalaludinii, Eubacterium ventriosum, Clostridium sp. FCB90-3, Prevotella nanceiensis, Clostridium fusiformis, Clostridium sp. BNL1100 and Eubacterium cylindroides) that, in some cases, showed opposite trends to their relative families. These results highlight the relevance of characterizing gut microbial population differences at species level and contribute to understand the plausible link between the 1 diet and specific gut bacterial species that are able to influence the inflammatory status, intestinal barrier function and obesity development. Keywords: gut microbiota, pyrosequencing, high-fat sucrose diet, short chain fatty acids, Erysipelotrich

Metabolic faecal fingerprinting of trans-resveratrol and quercetin following a high-fat sucrose dietary model using liquid chromatography coupled to high-resolution mass spectrometry

Faecal non‐targeted metabolomics deciphers metabolic end‐products resulting from the interactions among food, host genetics, and gut microbiota. Faeces from Wistar rats fed a high‐fat sucrose (HFS) diet supplemented with trans‐resveratrol and quercetin (separately or combined) were analysed by liquid chromatography coupled to high‐resolution mass spectrometry (LC‐HRMS). Metabolomics in faeces are categorised into four clusters based on the type of treatment. Tentative identification of significantly differing metabolites highlighted the presence of carbohydrate derivatives or conjugates (3‐phenylpropyl glucosinolate and dTDP‐D‐mycaminose) in quercetin group. The trans‐resveratrol group was differentiated by compounds related to nucleotides (uridine monophosphate and 2,4‐dioxotetrahydropyrimidine D‐ribonucleotide). Marked associations between bacterial species (Clostridium genus) and the amount of some metabolites were identified. Moreover, trans‐resveratrol and resveratrol‐derived microbial metabolites (dihydroresveratrol and lunularin) were also identified. Accordingly, this study confirms the usefulness of omics‐based techniques to discriminate individuals depending on the physiological effect of food constituents and represents an interesting tool to assess the impact of future personalized therapies

Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats

Diet‐induced obesity is associated to an imbalance in the normal gut microbiota composition. Resveratrol and quercetin, widely known for their health beneficial properties, have low bioavailability and, when reach the colon, they are targets of the gut microbial ecosystem. Hence, the use of these molecules in obesity might be considered as a potential strategy to modulate intestinal bacterial composition. The purpose of this study was to determine whether trans‐resveratrol and quercetin administration could counteract gut microbiota dysbiosis produced by high‐fat sucrose diet (HFS) and in turn, improve gut health. Wistar rats were randomized into four groups fed a HFS diet supplemented or not with trans‐resveratrol (15 mg/kg BW/day), quercetin (30 mg/kg BW/day) or a combination of both polyphenols at those doses. Administration of both polyphenols together prevented body‐weight gain and reduced serum insulin levels. Moreover, individual supplementation of trans‐resveratrol and quercetin effectively reduced serum insulin levels and insulin resistance. Quercetin supplementation generated a great impact on gut microbiota composition at different taxonomic levels, attenuating Firmicutes/Bacteroidetes ratio and inhibiting the growth of bacterial species previously associated to diet‐induced obesity (Erysipelotrichaceae, Bacillus, Eubacterium 1 cylindroides). Overall, the administration of quercetin was found to be effective in lessening HFS diet‐induced gut microbiota dysbiosis. In contrast, trans‐resveratrol supplementation alone or in combination with quercetin, scarcely modified the profile of gut bacteria, but acted at intestinal level altering the mRNA expression of tight‐junction proteins (TJPs) and inflammation associated genes

Life history study of the mirid Tupiocoris cucurbitaceus feeding on Tuta absoluta eggs: implications for biological control and its combination with inherited sterility

Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) is a key pest of tomato crops. Tupiocoris cucurbitaceus (Spinola) (Hemiptera: Miridae) is a neotropical predator capable of consuming T. absoluta eggs. We evaluated the life history traits of T. cucurbitaceus on three different diets: T. absoluta eggs from irradiated parental males and untreated parents, and Sitotroga cerealella (Olivier) (Lepidoptera: Gelechiidae) eggs (control). The nymphal development of T. cucurbitaceus was reached in 13 days with a similar survival for all diets (58–65%). Mirid female longevity and oviposition period were statistically similar when the diets consisted of T. absoluta eggs from untreated parents and S. cerealella eggs, although the number of nymphs laid was larger with the second diet. Moreover, mirid females feeding on T. absoluta eggs from untreated parents lived longer and laid double number of nymphs than when fed on T. absoluta eggs from irradiated parental males. The highest intrinsic rate of increase (rm) was observed for the S. cerealella eggs diet, while differences were not observed between the two types of T. absoluta eggs. These results indicate that the mirid could develop and reproduce by feeding exclusively on both types of T. absoluta eggs. As conclusion, the use of more environmentally friendly strategies to control this pest, such as the biological control and inherited sterility, is possible through the release of T. cucurbitaceus and irradiated T. absoluta individuals.Instituto de Microbiología y Zoología AgrícolaFil: Cagnotti, Cynthia Lorena. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Microbiología y Zoología Agrícola; ArgentinaFil: Arias, Ariel E. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Microbiología y Zoología Agrícola; ArgentinaFil: Ermantraut, Erika N. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Microbiología y Zoología Agrícola; ArgentinaFil: Andorno, Andrea Veronica. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Microbiología y Zoología Agrícola; ArgentinaFil: Viscarret, Mariana Mabel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Microbiología y Zoología Agrícola; ArgentinaFil: Lopez, Silvia Noemi. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Microbiología y Zoología Agrícola; Argentin

The combination of resveratrol and CLA does not increase the delipidating effect of each molecule in 3T3-L1 adipocytes

Introduction: Trans-10, cis-12 conjugated linoleic acid (CLA) and resveratrol have been shown to reduce TG content in cultured 3T3-L1 adipocyte acting on different pathways. In recent years, the method of simultaneously targeting several signal transduction pathways with multiple natural products in order to achieve additive or synergistic effects has been tested. However, the combined effect of both molecules on lipid metabolism has not been described before. Objective: The aim of the present work was to analyze the effect of the combination of trans-10, cis-12 CLA and resveratrol on TG accumulation as well as on FAS, HSL and ATGL expression in 3T3-L1 mature adipocytes, in order to assess a potential interaction between both molecules. Methods: For this purpose, 3T3-L1 mature adipocytes were treated with the two molecules, both separately and combined, in 10 and 100 μM for 20 hours. TG content and FAS, ATGL and HSL expression were measured by spectrophotometry and Real Time RT-PCR respectively. Results: Both doses of CLA and 100 M resveratrol decreased TG content in mature adipocytes. The combination of both molecules reduced TG accumulation to the same extent as each one separately. No change in FAS and HSL mRNA levels after CLA and resveratrol treatment was observed. ATGL was not modified by CLA but it was increased by resveratrol and by the combination. This combination did not increase the effect caused by resveratrol on its own. Conclusion: Lipolysis increase via ATGL is involved in the TG reduction induced by resveratrol and the combination of both molecules. The combination of these two molecules does not increase the efficacy of each molecule separately in mature adipocytes and thus it does not represent an advantage for obesity treatment or prevention

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)