The dietary consumption of grape and its products is associated with a lower incidence of degenerative diseases such as cardiovascular disease and certain types of cancers. Most recent interest has focused on the bioactive phenolic compounds in grape. Anthocyanins, flavanols, flavonols and resveratrol are the most important grape polyphenols because they possess many biological activities, such as antioxidant, cardioprotective, anticancer, anti-inflammation, antiaging and antimicrobial properties. This review summarizes current knowledge on the bioactivities of grape phenolics. The extraction, isolation and identification methods of polyphenols from grape as well as their bioavailability and potential toxicity also are included.

https://www.mdpi.com/1422-0067/11/2/622/pdf

Biological Activities of Polyphenols from Grapes

The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiology of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a critical node within the brain-gut axis. Mounting preclinical evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a "leaky gut" may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low-grade inflammation observed in disorders such as depression and the gut microbiome plays a critical role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clinical and preclinical evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function.

/pdf/breaking-down-the-barriers-the-gut-microbiome-intestinal-42wtsbv3fq.pdf

Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders

Evidence is accumulating that the gut microbiome is involved in the aetiology of obesity and obesity-related complications such as nonalcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes mellitus (T2DM). The gut microbiota is able to ferment indigestible carbohydrates (for example, dietary fibre), thereby yielding important metabolites such as short-chain fatty acids and succinate. Numerous animal studies and a handful of human studies suggest a beneficial role of these metabolites in the prevention and treatment of obesity and its comorbidities. Interestingly, the more distal colonic microbiota primarily ferments peptides and proteins, as availability of fermentable fibre, the major energy source for the microbiota, is limited here. This proteolytic fermentation yields mainly harmful products such as ammonia, phenols and branched-chain fatty acids, which might be detrimental for host gut and metabolic health. Therefore, a switch from proteolytic to saccharolytic fermentation could be of major interest for the prevention and/or treatment of metabolic diseases. This Review focuses on the role of products derived from microbial carbohydrate and protein fermentation in relation to obesity and obesity-associated insulin resistance, T2DM and NAFLD, and discusses the mechanisms involved.

Gut microbial metabolites in obesity, NAFLD and T2DM.

Disruptions in gut microbiota composition and function are increasingly implicated in the pathogenesis of obesity, insulin resistance, and type 2 diabetes mellitus. The functional output of the gut microbiota, including short-chain fatty acids and amino acids, are thought to be important modulators underlying the development of these disorders. Gut bacteria can alter the bioavailability of amino acids by utilization of several amino acids originating from both alimentary and endogenous proteins. In turn, gut bacteria also provide amino acids to the host. This could have significant implications in the context of insulin resistance and type 2 diabetes mellitus, conditions associated with elevated systemic concentrations of certain amino acids, in particular the aromatic and branched-chain amino acids. Moreover, several amino acids released by gut bacteria can serve as precursors for the synthesis of short-chain fatty acids, which also play a role in the development of obesity. In this review, we aim to compile the available evidence on the contribution of microbial amino acids to host amino acid homeostasis, and to assess the role of the gut microbiota as a determinant of amino acid and short-chain fatty acid perturbations in human obesity and type 2 diabetes mellitus.

https://www.mdpi.com/2072-6643/7/4/2930/pdf

The role of microbial amino acid metabolism in host metabolism.

https://www.gastrojournal.org/article/S0016-5085(13)01279-1/pdf

Therapeutic Potential of Fecal Microbiota Transplantation

Potential mechanisms for the emerging link between obesity and increased intestinal permeability

Intestinal permeability parameters in obese patients are correlated with metabolic syndrome risk factors

SCFA provide energy to the host and influence lipid and glucose metabolism, suggesting that they may have an impact on the occurrence of metabolic risk factors. The aim of the present study was to determine the concentration of SCFA in faeces of lean and obese individuals and to analyse whether associations between faecal SCFA and metabolic syndrome parameters are present. Lean (n 20) and obese (n 20) women of similar age (28·5 (sd 7·6) v. 30·7 (sd 6·5) years, P= 0·33) participated in the study. Anthropometric measurements, body composition, blood pressure and biochemical parameters were assessed. SCFA were extracted from faeces and quantified by GC. Blood pressure and blood glucose, although within the normal limits, were higher in the obese group compared to lean subjects (P< 0·05). Lower HDL concentration and higher insulin and homeostasis model assessment (HOMA) index were observed in the obese than in the lean group (P< 0·05). The median values of SCFA (% w/w) from the lean and obese groups were butyric (0·021 v. 0·044, P= 0·024), propionic (0·021 v. 0·051, P= 0·007) and acetic (0·03 v. 0·061, P= 0·01). SCFA correlated positively with metabolic syndrome risk factors such as adiposity, waist circumference and HOMA index (P< 0·05), and inversely with HDL (P< 0·05). Our results suggest that the higher faecal concentration of SCFA is associated with metabolic risk factors and thus may influence metabolic homeostasis.

/pdf/higher-level-of-faecal-scfa-in-women-correlates-with-4sa78c8aly.pdf

Higher level of faecal SCFA in women correlates with metabolic syndrome risk factors.

In this review, the influence of fat depots on insulin resistance and the main characteristics of metabolically obese normal-weight and metabolically healthy obese phenotypes are discussed. Medline/PubMed and Science Direct were searched for articles related to the terms metabolically healthy obesity, metabolically obese normal weight, adipose tissue, and insulin resistance. Normal weight and obesity might be heterogeneous in regard to their effects. Fat distribution and lower insulin sensitivity are the main factors defining phenotypes within the same body mass index. Although these terms are interesting, controversies about them remain. Future studies exploring these phenotypes will help elucidate the roles of adiposity and/or insulin resistance in the development of metabolic alterations.

Main characteristics of metabolically obese normal weight and metabolically healthy obese phenotypes

Introduction: Disturbances of the gut barrier function have been related to a variety of diseases, including intestinal and extra-intestinal diseases. The intestinal permeability tests are considered useful tools for evaluating disease severity and to follow-up patients after a therapeutic intervention and indirectly assess barrier function. Objective: The aims of this review were to highlight the possible factors underlying higher intestinal permeability and the clinical conditions that have been associated with this in different age range; and also provide some insight into methodological aspects. Results and discussion: Abnormal regulation of tight junction function is the main cause of altered intestinal barrier. The impaired barrier function results in higher permeation rates of administered probes through the intestinal mucosa. Lactulose and mannitol are one of the most commonly used probes. The innocuousness and easiness of intestinal permeability tests can be explored to expand the knowledge about the clinical situations in which intestinal barrier dysfunction can be an important feature. Many factors may influence the results of the test. Researchers and healthcare professionals should try to circumvent the possible pitfalls of the intestinal permeability tests to produce consistent evidences. The use of others markers of intestinal physiology may also contribute to understand the role of barrier function in different diseases.

/pdf/intestinal-permeability-measurements-general-aspects-and-38ebbqrp6b.pdf

Tatiana Fiche Salles Teixeira

Papers

Potential mechanisms for the emerging link between obesity and increased intestinal permeability

Intestinal permeability parameters in obese patients are correlated with metabolic syndrome risk factors

Higher level of faecal SCFA in women correlates with metabolic syndrome risk factors.

Main characteristics of metabolically obese normal weight and metabolically healthy obese phenotypes

Intestinal permeability measurements: general aspects and possible pitfalls