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

Recently, increased attention has been paid to the link between gut microbial composition and obesity. Gut microbiota is a source of endotoxins whose increase in plasma is related to obesity and insulin resistance through increased intestinal permeability in animal models; however, this relationship still needs to be confirmed in humans. That intestinal permeability is subject to change and that it might be the interface between gut microbiota and endotoxins in the core of metabolic dysfunctions reinforce the need to understand the mechanisms involved in these aspects to direct more efficient therapeutic approaches. Therefore, in this review, we focus on the emerging link between obesity and increased intestinal permeability, including the possible factors that contribute to increased intestinal permeability in obese subjects. We address the concept of intestinal permeability, how it is measured, and the intestinal segments that may be affected. We then describe 3 factors that may have an influence on intestinal permeability in obesity: microbial dysbiosis, dietary pattern (high-fructose and high-fat diet), and nutritional deficiencies. Gaps in the current knowledge of the role of Toll-like receptors ligands to induce insulin resistance, the routes for lipopolysaccharide circulation, and the impact of altered intestinal microbiota in obesity, as well as the limitations of current permeability tests and other potential useful markers, are discussed. More studies are needed to reveal how changes occur in the microbiota. The factors such as changes in the dietary pattern and the improvement of nutritional deficiencies appear to influence intestinal permeability, and impact metabolism must be examined. Also, additional studies are necessary to better understand how probiotic supplements, prebiotics, and micronutrients can improve stress-induced gastrointestinal barrier dysfunction and the influence these factors have on host defense. Hence, the topics presented in this review may be beneficial in directing future studies that assess gut barrier function in obesity.

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

BACKGROUND & AIMS Altered intestinal permeability has been shown to be associated with metabolic alterations in animal models of obesity, but not in humans. The aim of this study was to assess intestinal permeability in obese women and verify if there is any association with anthropometric measurements, body composition or biochemical variables. METHODS Twenty lean and twenty obese females participated in the study. Anthropometric measurements, body composition and blood pressure were assessed and biochemical analyses were performed. Administration of lactulose and mannitol followed by their quantification in urine was used to assess the intestinal permeability of volunteers. RESULTS The obese group showed lower HDL (p < 0.05), higher fasting glucose, insulin, HOMA index and lactulose excretion than the lean group (p < 0.05), suggesting increased paracellular permeability. Lactulose excretion showed positive correlation (p < 0.05) with waist and abdominal circumference. Blood insulin and the HOMA index also increased with the increase in mannitol and lactulose excretion and in the L/M ratio (p < 0.05). L/M ratio presented a negative correlation with HDL concentration (p < 0.05). CONCLUSIONS We demonstrated that intestinal permeability parameters in obese women are positively correlated with anthropometric measurements and metabolic variables. Therapeutic interventions focused on intestine health and the modulation of intestinal permeability should be explored in the context of obesity.

Higher level of faecal SCFA in women correlates 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.

Faecal levels of Bifidobacterium and Clostridium coccoides but not plasma lipopolysaccharide are inversely related to insulin and HOMA index in women

BACKGROUND & AIMS The abundance of specific microbes might be associated with plasma lipopolysaccharide and insulin levels. The aims were to quantify the abundance of specific microbes and plasma LPS in females and assess their association with anthropometric, body composition and biochemical measurements. METHODS Seventeen lean (BMI 19-24.99 kg/m(2)) and fifteen obese females (BMI > 30 kg/m(2)) participated. Anthropometry, body composition, food intake and biochemical analyses were assessed. Bacterial groups in faeces were analysed by qPCR method. RESULTS Lactobacillus plantarum prevalence was higher (p = 0.005) and its counts tended to be higher in lean vs. obese group (p = 0.06). Bifidobacterium genus, Bifidobacterium longum, Clostridium coccoides and Clostridium leptum counts were higher in lean women (p < 0.05); prevalence and counts of Akkermansia muciniphila tended to be higher in lean group (p = 0.09, p = 0.06, respectively). Plasma LPS levels were similar between the study groups (p > 0.05). No association was found between LPS and bacterial levels or insulin. Bifidobacteria and C. coccoides counts were inversely associated with insulin and HOMA index. CONCLUSIONS Abundance of specific microbes is distinct between obese and lean women, but is not associated with LPS level. Bifidobacterial and C. coccoides levels are associated with insulin sensitivity. These bacterial groups may be capable of modulating insulin action.

Grape extract and α-Tocopherol effect in cardiovascular disease model of Apo E -/- Mice

PURPOSE To verify the effect of consumption of grape extract isolated or combined with α-tocopherol supplementation on atherosclerosis model with Apo E -/- mice. METHODS After six weeks of atherogenic diet, Apo E -/- mice were divided into the following groups: Control, Grape, Tocopherol and Grape plus Tocopherol. The treatment progressed for 11 weeks when animals were submitted to euthanasia. RESULTS All the treatments presented hypocholesterolemic effect with reduction of serum and liver cholesterol levels. This effect was parallel to an increase in the fecal excretion of cholesterol. There was also a higher fecal excretion of saturated fatty acids in groups receiving grape extract or α-tocopherol. All the groups treated presented a tendency to show higher levels of vitamin E. The fatty acid profile showed a tendency for monounsaturated fatty acid preservation after grape extract and α-tocopherol consumption. Morphological analysis revealed a lower degree of evolution of the atherosclerotic plaque of the animals that were fed α-tocopherol combined with grape extract, even when no difference was found in the size of the largest lesion. CONCLUSION A synergistic effect between the polyphenols and α-tocopherol was observed, resulting in diminished evolution of atherosclerosis and a greater beneficial effect on atherosclerosis than the isolated consumption of antioxidants.

Intestinal permeability measurements: general aspects and possible pitfalls

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.

Effect of a high-fat meal containing conventional or high-oleic peanuts on post-prandial lipopolysaccharide concentrations in overweight/obese men.

BACKGROUND An increased plasma lipopolysaccharide (LPS) concentration may favour metabolic disorders such as insulin resistance. The meal composition influences plasma LPS concentrations. The present study aimed to investigate the effect of the acute consumption of a high-fat meal (49% of energy from fat) containing conventional or high-oleic peanuts on post-prandial LPS concentrations and its relationship with lipaemia and insulinaemia in overweight and obese men. METHODS The test meal consisted of a shake containing conventional peanuts (CVP; n = 21), high-oleic peanuts (HOP; n = 23) or a control biscuit (CT; n = 21). Blood samples were collected in the fasting state and 1, 2 and 3 h post-prandially. LPS, insulin, lipids and glucose concentrations were assessed. RESULTS LPS concentrations were lower in CVP [mean (SE) 0.7 (0.5) EU mL(-1) ] and HOP [1.0 (0.9) EU mL(-1) ] groups compared to CT [1.6 (1.2) EU mL(-1) ] at 3 h post-prandially. Triacylglycerol and insulin concentrations increased in all groups. Triacylglycerol started to increase only after 2 h in the CVP and HOP groups. LPS correlated positively with triacylglycerol. Insulin returned to basal concentrations at 3 h only in the CVP and HOP groups. CONCLUSIONS The acute consumption of peanuts delayed the increase in serum triacylglycerol and favoured the quicker return of insulin to basal concentrations, especially in the CVP group. Our results suggest that the consumption of conventional or high-oleic peanuts may help to reduce the risk of endotoxaemia and metabolic disorders.

Soybean Oil: How Good or How Bad in Comparison with Other Dietary Oils in the Context of Colon Cancer

Soybeans (Glycine Max) are one of the oldest crops cultivated around the world, and in Asia soyfoods have been consumed for more than 1000 years. The soybean was popularized because of its high content of protein and good percentage of lipids. World consumption of soybeans in 2008 was over 221 million metric tons, with approximately 50% of this supply coming from US production, where over 77 million ha are planted annually. Soybeans are desired in the market as a source of protein and oil. Nowadays, soy has a huge economic importance because the beans are very versatile and can be used not only for human and animal nutrition but also for industrial products (Clemente & Cahoon 2009). Many beneficial effects of soy components such as soy protein, isoflavones, phytosterols, inositol hexaphosphate and saponins have been suggested, including the beneficial role for inhibition of tumor development in animal models (Hawrylewicz, Zapata et al. 1995). This has stimulated, in only the last 30 years, soybean introduction into western cultures and diets as different sub-products (Golbitz 1995). These products are usually fermented (tempeh, miso, soy sauces, natto, fermented tofu) or non-fermented (fresh soybeans, whole dry soybeans, soy nuts, soy sprouts, whole-fat soy flour, soymilk, tofu, soy protein, soy oil). One of the most used nonfermented subproduct is the soybean oil. The oil represents approximately 20% of the grain and is influenced by both genotype and environmental factors, and in some countries this is the main sub-product utilized in the diet (Clemente & Cahoon 2009). Soybean oil is a representative source of lipids in human nutrition. There are proposed mechanisms that explain lipids involvement in cancer development, especially colorectal cancer (CRC). Thus, comparing soybean oil composition with other oils is a discussion that is relevant in the context of CRC, once this is a public health concern.