Effect of a carotenoid-producing Bacillus strain on intestinal barrier integrity and systemic delivery of carotenoids : a randomised trial in animals and humans

The aim of the present study was to investigate effects of the carotenoid-producing Bacillus indicus strain PD01 on intestinal barrier function and its ability to survive passage through the gastrointestinal tract and to assess systemic bioavailability of these carotenoids in vivo. As model for impaired barrier function, 16 early weaned piglets were randomly assigned to a control diet or control diet with PD01 for 23 days. In addition, 67 overweight/obese, otherwise healthy individuals were randomly assigned to groups receiving PD01 or placebo for 6 weeks. PD01 survived passage through the gastrointestinal tract in piglets and human subjects and resulted in significant accumulation of PD01 derived carotenoids (methyl-glycosyl-apo-8'-lycopenoate and glycosyl-apo-8'- lycopene) in human plasma after 3- and 6-weeks supplementation versus baseline (0.044 and 0.076 vs 0 mu M, respectively; p = 0.104). In summary, PD01 survived transit through the gastrointestinal tract, resulted in systemic carotenoid accumulation and improved compromised barrier function outcomes

Nutritional interventions focusing on gastrointestinal and metabolic health

This dissertation examined the effects of various nutritional interventions on the gastrointestinal and metabolic health of healthy, overweight and obese individuals. Aspergillus niger prolyl endoprotease (AN-PEP) is capable of processing nutritional gluten and efficiently breaking it down in the stomach of healthy volunteers before the gluten reaches the small intestine. The changing composition of intestinal microbiotics through nutrition is an interesting way to improve the intestinal barrier and to treat or prevent the development and progression of chronic illnesses. Arabinoxylan (AX), non-digestible carbohydrates found in wheat, are capable of changing microbiotic activity, which can have positive effects on both the intestinal barrier and the immune system. Large-scale studies have revealed that flavonoid-rich products have a positive effect on cardiovascular diseases and their associated risks, as well as on gastrointestinal parameters. The studies examined the effects of hesperidin, a flavonoid found in the peels of citrus fruits. They found that hesperidin can improve vascular function and potentially blood pressure as well in individuals with relatively healthy blood vessels. It could also have a positive effect on microbiotic activity

Citrus Extract High in Flavonoids Beneficially Alters Intestinal Metabolic Responses in Subjects with Features of Metabolic Syndrome †

The objective of this study was to investigate the effects of a citrus extract rich in citrus flavonoids on intestinal metabolic responses in subjects with features of metabolic syndrome, in an in vitro colon fermentation system (TIM-2) and fecal samples obtained from human subjects in an in vivo trial. In the TIM-2 system inoculated with fecal samples of volunteers with features of metabolic syndrome, continuous citrus extract supplementation (500 mg/day) resulted in increased cumulative short-chain fatty acid (SCFA) levels compared to the control condition, which was mainly due to increased production of butyrate, acetate, and valerate. In human volunteers, 12 weeks of daily supplementation with 500 mg citrus extract resulted in a significant shift in the SCFA profile towards more butyrate (p = 0.022) compared to the placebo group. Furthermore, there was a trend towards a reduction in fecal calprotectin levels, a marker for intestinal inflammation, compared to the placebo (p = 0.058). Together, these results suggest that citrus extract intake may have a positive effect on intestinal metabolic responses and through this, on host health in subjects with features of metabolic syndrome. Further research is needed to provide more insight into the potential underlying mechanisms and to study effects on clinical parameters

A critical evaluation of in vitro hesperidin 2S bioavailability in a model combining luminal (microbial) digestion and Caco-2 cell absorption in comparison to a randomized controlled human trial

Scope: Bioavailability strongly determines polyphenol bioactivity, and is strongly influenced by food matrix, enzymatic and microbial degradation, and gastrointestinal absorption. To avoid human trials for pre-screening of polyphenol bioavailability, studies have focused on in vitro model development. Nevertheless, their predictive value for bioavailability can be questioned. Method and results: We used the orange flavonoid hesperidin 2S to validate a model combining digestion in the simulator of the human intestinal microbial ecosystem (SHIME) and Caco-2 cell transport, with a human intervention study. In vitro, hesperidin was resistant to degradation in the stomach and small intestine, but was rapidly deconjugated on reaching the proximal colon. Extensive and colon-region-specific degradation to smaller phenolics was observed. Hydrocaffeic and dihydroisoferulic acid accumulated in proximal, and hydroferulic acid in distal colon. Caco-2 transport was the highest for dihydroisoferulic acid. In humans, plasma and urine hesperetin-glucuronide levels increased significantly, whereas the impact on small phenolics was limited. Conclusions: In the combined in vitro model, smaller phenolics strongly accumulated, whereas in humans, hesperetin conjugates were the main bioavailable compounds. Future in vitro model development should focus on simulating faster polyphenol absorption and elimination of smaller phenolics to improve their predictive value of in vivo polyphenol bioavailability

Randomized clinical trial on the efficacy of hesperidin 2S on validated cardiovascular biomarkers in healthy overweight individuals

Background: Endothelial dysfunction (ED) is involved in the development of atherosclerosis. Hesperidin, a citrus flavonoid with antioxidant and other biological properties, potentially exerts beneficial effects on endothelial function (EF). Objective: We investigated the effect of hesperidin 2S supplementation on EF in overweight individuals. Design: This was a randomized, double-blind, placebo-controlled study in which 68 individuals were randomly assigned to receive hesperidin 2S (450 mg/d) or a placebo for 6 wk. At baseline and after 6 wk of intervention, flow-mediated dilation (FMD), soluble vascular adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), soluble P-selectin (sP-selectin), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were assessed. Acute, reversible ED was induced by intake of a high-fat meal (HFM). A second FMD scan was performed 2 h postprandially, and adhesion molecules were assessed 2 and 4 h postprandially. An additional exploratory analysis was performed in subjects with baseline FMD >= 3%. Results: No significant change in fasting or postprandial FMD was observed after 6 wk of hesperidin intake compared with placebo intake. However, there was a trend for a reduction of sVCAM-1, sICAM-1, sP-selectin, SBP, and DBP after 6 wk of hesperidin treatment. In the FMD >= 3% group, hesperidin protected individuals from postprandial ED (P = 0.050) and significantly downregulated sVCAM-1 and sICAM-1 (all P <= 0.030). The results reported in the current article were not adjusted for multiplicity. Conclusions: Six weeks of consumption of hesperidin 2S did not improve basal or postprandial FMD in our total study population. There was a tendency toward a reduction of adhesion molecules and a decrease in SBP and DBP. Further exploratory analyses revealed that, in subjects with baseline FMD >= 3%, hesperidin 2S improved ED after an HFM and reduced adhesion molecules. These results indicate the cardiovascular health benefits of hesperidin 2S in overweight and obese individuals with a relatively healthy endothelium. This trial was registered at clinicaltrials.gov as NCT02228291