Diet-induced obesity is associated with low-grade inflammation, which, in most cases, leads to the development of metabolic disorders, primarily insulin resistance and type 2 diabetes. Although prior studies have implicated the adipose tissue as being primarily responsible for obesity-associated inflammation, the latest discoveries have correlated impairments in intestinal immune homeostasis and the mucosal barrier with increased activation of the inflammatory pathways and the development of insulin resistance. Therefore, it is essential to define the mechanisms underlying the obesity-associated gut alterations to develop therapies to prevent and treat obesity and its associated diseases. Flavonoids appear to be promising candidates among the natural preventive treatments that have been identified to date. They have been shown to protect against several diseases, including CVD and various cancers. Furthermore, they have clear anti-inflammatory properties, which have primarily been evaluated in non-intestinal models. At present, a growing body of evidence suggests that flavonoids could exert a protective role against obesity-associated pathologies by modulating inflammatory-related cellular events in the intestine and/or the composition of the microbiota populations. The present paper will review the literature to date that has described the protective effects of flavonoids on intestinal inflammation, barrier integrity and gut microbiota in studies conducted using in vivo and in vitro models.

The gastrointestinal alterations associated with the consumption of an obesogenic diet, such as inflammation, permeability impairment and oxidative stress, have been poorly explored in both diet-induced obesity (DIO) and genetic obesity. The aim of the present study was to examine the impact of an obesogenic diet on the gut health status of DIO rats in comparison with the Zucker (fa/fa) rat leptin receptor-deficient model of genetic obesity over time. For this purpose, female Wistar rats (n 48) were administered a standard or a cafeteria diet (CAF diet) for 12, 14·5 or 17 weeks and were compared with fa/fa Zucker rats fed a standard diet for 10 weeks. Morphometric variables, plasma biochemical parameters, myeloperoxidase (MPO) activity and reactive oxygen species (ROS) levels in the ileum were assessed, as well as the expressions of proinflammatory genes (TNF-α and inducible nitric oxide synthase (iNOS)) and intestinal permeability genes (zonula occludens-1, claudin-1 and occludin). Both the nutritional model and the genetic obesity model showed increased body weight and metabolic alterations at the final time point. An increase in intestinal ROS production and MPO activity was observed in the gastrointestinal tracts of rats fed a CAF diet but not in the genetic obesity model. TNF-α was overexpressed in the ileum of both CAF diet and fa/fa groups, and ileal inflammation was associated with the degree of obesity and metabolic alterations. Interestingly, the 17-week CAF group and the fa/fa rats exhibited alterations in the expressions of permeability genes. Relevantly, in the hyperlipidic refined sugar diet model of obesity, the responses to chronic energy overload led to time-dependent increases in gut inflammation and oxidative stress.

This study provides evidence for the ameliorative effect of a proanthocyanidin extract on high-fat/high-carbohydrate diet-induced intestinal alterations, specifically reducing intestinal inflammation and oxidative stress and suggesting a protection against a barrier defect.

Obesity is highly associated with the pathologies included in the concept of the Metabolic Syndrome. Grape-seed proanthocyanins (GSPE) have showed very positive effects against all these metabolic disruptions; however, there is, as yet, no consensus about their effectiveness against an obesogenic challenge, such as a cafeteria diet. We determined the effectiveness of a dose of 500 mg GSPE/kg b.w. (body weight) against the obesogenic effects of a 17-week cafeteria diet, administered as a sub-chronic treatment, 10–15 days before, intermittently and at the end of the diet, in Wistar rats. Body weight, adiposity, indirect calorimetry and plasma parameters were analyzed. GSPE pre-treatment showed a long-lasting effect on body weight and adiposity that was maintained for seven weeks after the last dose. A corrective treatment was administered for the last two weeks of the cafeteria diet intervention; however, it did not effectively correct any of the parameters assessed. The most effective treatment was an intermittent GSPE dosage, administered every second week during the cafeteria diet. This limited body weight gain, adiposity and most lipotoxic effects. Our results support the administration of this GSPE dose, keeping an intermittent interval between dosages longer than every second week, to improve obesogenic disruptions produced by a cafeteria diet.

Scope Intestinal dysfunction consists of a defective barrier function, which allows the influx of luminal endotoxins, thus causing intestinal inflammation. Proanthocyanidins are natural bioactive compounds that could modulate intestinal dysfunction. This study analyzes the protective effects of proanthocyanidins in a rat model of intestinal dysfunction. Methods and results To investigate the preventive effects of both high dietary (75 mg kg–1 body weight) and pharmacological (375 mg kg–1 body weight) oral doses of proanthocyanidins (GSPE), rat intestinal dysfunction is induced with LPS (i.p.). In vivo intestinal permeability (ovalbumin [OVA] assay) and systemic inflammation and endotoxemia (TNF‐α and LPS plasma levels) are assessed. Intestinal inflammation and oxidative stress are determined using myeloperoxidase (MPO), cyclooxygenase‐2 (COX‐2) activities, and reactive oxygen species (ROS) levels, respectively. Ileal gene expression of permeability/inflammatory genes is analyzed. LPS administration induces intestinal permeability, inflammation, and oxidative stress. GSPE normalizes in vivo OVA levels. In the small intestine, the GSPE treatment decreases MPO and COX‐2 activities; modulates the ileum inflammatory and permeability proteins gene expression; and in the large intestine, prevents increase of ROS levels. Conclusions Proanthocyanidins, at nutritional and pharmacological doses, prevents endotoxin‐induced‐intestinal inflammation, permeability, and oxidative stress in rats differentially in each intestinal section. Proanthocyanidins are nutritional‐therapeutic novel candidates for preventing intestinal dysfunction.