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 dietinduced 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.

Gut microbiota plays a key role in host physiology and metabolism. Indeed, the relevance of a well-balanced gut microbiota composition to an individual´s health status is essential for the person's well-being. Currently, investigations are focused on analyzing the effects of pre-and probiotics as new therapeutic tools to counteract the disruption of intestinal bacterial balance occurring in several diseases. Polyphenols exert a wide range of beneficial health effects. However, although specific attention has been paid in recent years to the function of this "biological entity" in the metabolism of polyphenols, less is known about the modulatory capacity of these bioactive compounds on gut microbiota composition. This review provides an overview of the latest investigations carried out with pure polyphenols, extracts rich in polyphenols and polyphenol-rich dietary sources (such as cocoa, tea, wine, soy products and fruits), and critically discusses the consequences to gut microbiota composition which are produced.

Importance of the field: The increasing prevalence of type 2 diabetes mellitus and the negative clinical outcomes observed with the commercially available anti-diabetic drugs have led to the investigation of new therapeutic approaches focused on controlling postprandrial glucose levels. The use of carbohydrate digestive enzyme inhibitors from natural resources could be a possible strategy to block dietary carbohydrate absorption with less adverse effects than synthetic drugs. Areas covered in this review: This review covers the latest evidence regarding in vitro and in vivostudies in relation to pancreatic alpha-amylase inhibitors of plant origin, and presents bioactive compounds of phenolic nature that exhibit anti-amylase activity.What the reader will gain: The state of the art of the search for new pancreatic alpha amylase inhibitors of plant origin for the treatment of type 2 diabetes mellitus.Take home message: Pancreatic alpha-amylase inhibitors from traditional plant extracts are a promising tool for diabetes treatment. Many studies have confirmed the alpha-amylase inhibitory activity of plants and their bioactive compounds in vitro, but few studies corroborate these findings in rodents and very few in humans. Thus, despite some encouraging results, more research is required for developing a valuable anti-diabetic therapy using pancreatic alpha-amylase inhibitors of plant origin.Keywords: alpha-amylase; flavonoids; proanthocyanidins; tannins; type 2 diabetes mellitus 2 IntroductionDiabetes mellitus is one of the world´s major diseases, with an estimation of 347 million adults affected in 2011 (1). Type 2 diabetes mellitus, by far the most common type, is a metabolic disorder of multiple etiology characterized by carbohydrate, lipid and protein metabolic disorders that includes defects in insulin secretion, almost always with a major contribution of insulin resistance (2). These abnormalities could lead to lesions such as retinopathy, nephropathy, neuropathy, and angiopathy (3).In this context, the inhibition of carbohydrate digestive enzymes is considered a therapeutic tool for the treatment of type 2 diabetes (4). The most important digestive enzyme is pancreatic alpha-amylase (EC 3.2.1.1), a calcium metalloenzyme that catalyzes the hydrolysis of the alpha-1,4 glycosidic linkages of the starch, amylose, amylopectin, glycogen, and various maltodextrins and is responsible of most of starch digestion in humans. A second enzyme named alpha-glucosidase or maltase (EC 3.2.1.20) catalyzes the final step of the digestive process of carbohydrates acting upon 1,4-alpha bonds and giving as a result glucose (4).A positive correlation between human pancreatic alpha-amylase (HPA) activity and the increase in postprandial glucose levels has been shown, demonstrating the relevance of suppressing postprandial hyperglycemia (PPHG) in the treatment of type 2 diabetes (5). The ability of the alpha-amylase enzyme inhibitors to avoid dietary starch to be digested and absorbed in the organism has allowed to designat...

These findings suggest that some bacterial genders involved in gut barrier function, are promoted by phytochemicals present in rhubarb extract, and could therefore be involved in the modulation of the susceptibility to hepatic diseases linked to acute alcohol consumption.