Colon-available mango (poly)phenols exhibit mitigating effects on the intestinal barrier function in human intestinal cell monolayers under inflammatory conditions.

This study investigated the impact of in vivo available colon-mango (poly)phenols on stress-induced impairment of intestinal barrier function. Caco-2/HT29-MTX cells were incubated with six extracts of ileal fluid collected pre- and 4-8 h post-mango consumption before being subjected to inflammatory stress. (Poly)phenols in ileal fluids were analysed by UHPLC-HR-MS. Epithelial barrier function was monitored by measurement of trans-epithelial electrical resistance (TEER) and the production of selected inflammatory markers (interleukin-8 (IL-8) and nitric oxide (NO)) and the major mucin of the mucosal layer (MUC2). Post-mango intake ileal fluids contained principally benzoic acids, hydroxybenzenes and galloyl derivatives. There was a high interindividual variability in the levels of these compounds, which was reflected by the degree of variability in the protective effects of individual ileal extracts on inflammatory changes in the treated cell cultures. The 24 h treatment with non-cytotoxic doses of extracts of 4-8 h post-mango intake ileal fluid significantly reduced the TEER decrease in monolayers treated with the inflammatory cytomix. This effect was not associated with changes in IL-8 expression and secretion or claudine-7 expression. The mango derived-ileal fluid extract (IFE) also mitigated cytomix-dependent nitrite secretion, as a proxy of NO production, and the MUC2 reduction observed upon the inflammatory challenge. These insights shed light on the potential protective effect of mango (poly)phenols on the intestinal barrier exposed to inflammatory conditions.

Exploring and disentangling the production of potentially bioactive phenolic catabolites from dietary (poly)phenols, phenylalanine, tyrosine and catecholamines.

Following ingestion of fruits, vegetables and derived products, (poly)phenols that are not absorbed in the upper gastrointestinal tract pass to the colon, where they undergo microbiota-mediated ring fission resulting in the production of a diversity of low molecular weight phenolic catabolites, which appear in the circulatory system and are excreted in urine along with their phase II metabolites. There is increasing interest in these catabolites because of their potential bioactivity and their use as biomarkers of (poly)phenol intake. Investigating the fate of dietary (poly)phenolics in the colon has become confounded as a result of the recent realisation that many of the phenolics appearing in biofluids can also be derived from the aromatic amino acids, l-phenylalanine and l-tyrosine, and to a lesser extent catecholamines, in reactions that can be catalysed by both colonic microbiota and endogenous mammalian enzymes. The available evidence, albeit currently rather limited, indicates that substantial amounts of phenolic catabolites originate from phenylalanine and tyrosine, while somewhat smaller quantities are produced from dietary (poly)phenols. This review outlines information on this topic and assesses procedures that can be used to help distinguish between phenolics originating from dietary (poly)phenols, the two aromatic amino acids and catecholamines.

Existing and Future Strategies to Manipulate the Gut Microbiota With Diet as a Potential Adjuvant Treatment for Psychiatric Disorders.

Nutrition and diet quality play key roles in preventing and slowing cognitive decline and have been linked to multiple brain disorders. This review compiles available evidence from preclinical studies and clinical trials on the impact of nutrition and interventions regarding major psychiatric conditions and some neurological disorders. We emphasize the potential role of diet-related microbiome alterations in these effects and highlight commonalities between various brain disorders related to the microbiome. Despite numerous studies shedding light on these findings, there are still gaps in our understanding due to the limited availability of definitive human trial data firmly establishing a causal link between a specific diet and microbially mediated brain functions and symptoms. The positive impact of certain diets on the microbiome and cognitive function is frequently ascribed with the anti-inflammatory effects of certain microbial metabolites or a reduction of proinflammatory microbial products. We also critically review recent research on pro- and prebiotics and nondietary interventions, particularly fecal microbiota transplantation. The recent focus on diet in relation to brain disorders could lead to improved treatment outcomes with combined dietary, pharmacological, and behavioral interventions.

Moving towards in pouch diagnostics for ostomy patients: exploiting the versatility of laser induced graphene sensors.

The development of a 3D printed sensor for direct incorporation within stoma pouches is described. Laser induced graphene scribed on either side of polyimide film served as the basis of a 2 electrode configuration that could be integrated within a disposable pouch sensor for the periodic monitoring of ileostomy fluid pH. The graphene sensors were characterised using electron microscopy, Raman spectroscopy, DekTak profilometry with the electrochemical properties investigated using both cyclic and square wave voltammetry. Adsorbed riboflavin was employed as a biocompatible redox probe for the voltammetric measurement of pH. The variation in peak position with pH was found to be linear over pH 3-8 with a sub Nernstian response (43 mV/pH). The adsorbed probe was found to be reversible and exhibited minimal leaching through repeated scanning. The performance of the system was assessed in a heterogeneous bacterial fermentation mixture simulating ileostomy fluid with the pH recorded before and after 96 h incubation. The peak profile in the bacterial medium provided an unambiguous signal free from interference with the calculated pH before and after incubation (pH 5.3 to 3.66) in good agreement with that obtained with commercial pH probes. Supplementary Information: The online version contains supplementary material available at 10.1007/s10853-023-08881-x.

Excretion by subjects on a low (poly)phenol diet of phenolic gut microbiota catabolites sequestered in tissues or associated with catecholamines and surplus amino acids.

Phenolic catabolites excreted by fasting subjects with a functioning colon and ileostomists on a low (poly)phenol diet have been investigated. Urine was collected over a 12 h fasting period after adherence to a low (poly)phenol diet for 36 h. UHPLC-HR-MS quantified 77 phenolics. Some were present in the urine of both groups in similar trace amounts and others were excreted in higher amounts by participants with a colon indicating the involvement of the microbiota. Most were present in sub- or low-µmol amounts, but hippuric acid dominated accounting on average for 60% of the total for both volunteer categories indicating significant production from sources other than non-nutrient dietary (poly)phenols. The potential origins of the phenolics associated with the low (poly)phenol diet, include endogenous catecholamines, surplus tyrosine and phenylalanine, and washout of catabolites derived from pre-study intakes of non-nutrient dietary (poly)phenols.

Flavan-3-ol-methylxanthine interactions: Modulation of flavan-3-ol bioavailability in volunteers with a functional colon and an ileostomy.

Flavan-3-ols, including the flavan-3-ol monomer (-)-epicatechin, are dietary bioactives known to mediate beneficial cardiovascular effects in humans. Recent studies showed that flavan-3-ols could interact with methylxanthines, evidenced by an increase in flavan-3-ol bioavailability with a concomitant increase in flavan-3-ol intake-mediated vascular effects. This study aimed at elucidating flavan-3-ol-methylxanthine interactions in humans in vivo by evaluating the specific contributions of theobromine and caffeine on flavan-3-ol bioavailability. In ileostomists, the effect of methylxanthines on the efflux of flavan-3-ol metabolites in the small intestine was assessed, a parameter important to an understanding of the pharmacokinetics of flavan-3-ols in humans. In a randomized, controlled, triple cross-over study in volunteers with a functional colon (n = 10), co-ingestion of flavan-3-ols and cocoa methylxanthines, mainly represented by theobromine, increased peak circulatory levels (Cmax) of flavan-3-ols metabolites (+21 ± 8%; p < 0.05). Conversely, caffeine did not mediate a statistically significant effect on flavan-3-ol bioavailability (Cmax = +10 ± 8%, p = n.s.). In a subsequent randomized, controlled, double cross-over study in ileostomists (n = 10), cocoa methylxanthines did not affect circulatory levels of flavan-3-ol metabolites, suggesting potential differences in flavan-3-ol bioavailability compared to volunteers with a functional colon. The main metabolite in ileal fluid was (-)-epicatechin-3'-sulfate, however, no differences in flavan-3-ol metabolites in ileal fluid were observed after flavan-3-ol intake with and without cocoa methylxanthines. Taken together, these results demonstrate a differential effect of caffeine and theobromine in modulating flavan-3-ol bioavailability when these bioactives are co-ingested. These findings should be considered when comparing the effects mediated by the intake of flavan-3-ol-containing foods and beverages and the amount and type of methylxanthines present in the ingested matrixes. Ultimately, these insights will be of value to further optimize current dietary recommendations for flavan-3-ol intake. CLINICAL TRIAL REGISTRATION NUMBER: This work was registered at clinicaltrials.gov as NCT03526107 (study part 1, volunteers with functional colon) and NCT03765606 (study part 2, volunteers with an ileostomy).

Long-term supplementation with anthocyanin-rich or -poor Rubus idaeus berries does not influence microvascular architecture nor cognitive outcome in the APP/PS-1 mouse model of Alzheimer's disease.

Disruption of microvascular architecture is a common pathogenic mechanism in the progression of Alzheimer's disease (AD). Given the anti-angiogenic activity of berry (poly)phenols, we investigated whether long-term feeding of Rubus idaeus (raspberries) could ameliorate cerebral microvascular pathology and improve cognition in the APP/PS-1 mouse model of AD. Male C57Bl/6J mice (50 wild type, 50 APP/PS-1) aged 4-months were fed for 24-weeks, with a normal diet enriched with either 100 mg/day glucose (control diet) or supplemented with glucose and freeze-dried anthocyanin-rich (red) or -poor (yellow) raspberries (100 mg/day) and assessed/sampled post intervention. Cerebral microvascular architecture of wild-type mice was characterised by regularly spaced capillaries with uniform diameters, unlike APP/PS-1 transgenic mice which showed dysregulated microvascular architecture. Long-term feeding of raspberries demonstrated limited modulation of microbiota and no substantive effect on microvascular architecture or cognition in either mice model although changes were evident in endogenous cerebral and plasmatic metabolites.

The future is bright: Biofortification of common foods can improve vitamin D status.

Vitamin D deficiency is a global concern, linked to suboptimal musculoskeletal health and immune function, with status inadequacies owing to variations in UV dependent cutaneous synthesis and limited natural dietary sources. Endogenous biofortification, alongside traditional fortification and supplement usage is urgently needed to address this deficit. Evidence reviewed in the current article clearly demonstrates that feed modification and UV radiation, either independently or used in combination, effectively increases vitamin D content of primary produce or ingredients, albeit in the limited range of food vehicles tested to date (beef/pork/chicken/eggs/fish/bread/mushrooms). Fewer human trials have confirmed that consumption of these biofortified foods can increase circulating 25-hydroxyvitamin D [25(OH)D] concentrations (n = 10), which is of particular importance to avoid vitamin D status declining to nadir during wintertime. Meat is an unexplored yet plausible food vehicle for vitamin D biofortification, owing, at least in part, to its ubiquitous consumption pattern. Consumption of PUFA-enriched meat in human trials demonstrates efficacy (n = 4), lighting the way for exploration of vitamin D-biofortified meats to enhance consumer vitamin D status. Response to vitamin D-biofortified foods varies by food matrix, with vitamin D3-enriched animal-based foods observing the greatest effect in maintaining or elevating 25(OH)D concentrations. Generally, the efficacy of biofortification appears to vary dependent upon vitamer selected for animal feed supplementation (vitamin D2 or D3, or 25(OH)D), baseline participant status and the bioaccessibility from the food matrix. Further research in the form of robust human clinical trials are required to explore the contribution of biofortified foods to vitamin D status.

Lasered Graphene Microheaters Modified with Phase-Change Composites: New Approach to Smart Patch Drug Delivery.

The combination of paraffin wax and O,O'-bis(2-aminopropyl) polypropylene glycol-block-polyethylene glycol-block-polypropylene glycol was used as a phase-change material (PCM) for the controlled delivery of curcumin. The PCM was combined with a graphene-based heater derived from the laser scribing of polyimide film. This assembly provides a new approach to a smart patch through which release can be electronically controlled, allowing repetitive dosing. Rather than relying on passive diffusion, delivery is induced and terminated through the controlled heating of the PCM with transfer only occurring when the PCM transitions from solid to liquid. The material properties of the device and release characteristics of the strategy under repetitive dosing are critically assessed. The delivery yield of curcumin was found to be 3.5 µg (4.5 µg/cm2) per 3 min thermal cycle.

Ex Vivo Fecal Fermentation of Human Ileal Fluid Collected After Wild Strawberry Consumption Modulates Human Microbiome Community Structure and Metabolic Output and Protects Against DNA Damage in Colonic Epithelial Cells.

SCOPE: Wild strawberries (Fragaria vesca) are richer in (poly)phenols than common commercial strawberry varieties, e.g., Fragaria × ananassa. (Poly)phenols and their microbiota-derived metabolites are hypothesized to exert bioactivity within the human gut mucosa. To address this, the effects of wild strawberries are investigated with respect to their bioactivity and microbiota-modulating capacity using both in vitro and ex vivo approaches. METHODS AND RESULTS: Ileal fluids collected pre- (0h) and post-consumption (8h) of 225 g wild strawberries by ileostomates (n = 5) and also in vitro digested strawberry varieties (Fragaria vesca and Fragaria × ananassa Duchesne) supernatants are collected. Subsequent fermentation of these supernatants using an in vitro batch culture proximal colon model reveals significant treatment-specific changes in microbiome community structure in terms of alpha but not beta diversity at 24 h. Nutri-kinetic analysis reveals a significant increase in the concentration of gut microbiota catabolites, including 3-(4hydroxyphenyl)propionic acid, 3-(3-hydroxyphenyl)propanoic acid, and benzoic acid. Furthermore, post-berry ileal fermentates (24 h) significantly (p < 0.01) decrease DNA damage (% Tail DNA, COMET assay) in both HT29 cells (∼45%) and CCD 841 CoN cells (∼25%) compared to untreated controls. CONCLUSIONS: Post berry consumption fermentates exhibit increased overall levels of (poly)phenolic metabolites, which retains their bioactivity, reducing DNA damage in colonocytes.

Low-Molecular-Weight Seaweed-Derived Polysaccharides Lead to Increased Faecal Bulk but Do Not Alter Human Gut Health Markers.

Seaweeds are potentially sustainable crops and are receiving significant interest because of their rich bioactive compound content; including fatty acids, polyphenols, carotenoids, and complex polysaccharides. However, there is little information on the in vivo effects on gut health of the polysaccharides and their low-molecular-weight derivatives. Herein, we describe the first investigation into the prebiotic potential of low-molecular-weight polysaccharides (LMWPs) derived from alginate and agar in order to validate their in vivo efficacy. We conducted a randomized; placebo-controlled trial testing the impact of alginate and agar LWMPs on faecal weight and other markers of gut health and on composition of gut microbiota. We show that these LMWPs led to significantly increased faecal bulk (20-30%). Analysis of gut microbiome composition by sequencing indicated no significant changes attributable to treatment at the phylum and family level, although FISH analysis showed an increase in Faecalibacterium prausnitzii in subjects consuming agar LMWP. Sequence analysis of gut bacteria corroborated with the FISH data, indicating that alginate and agar LWMPs do not alter human gut microbiome health markers. Crucially, our findings suggest an urgent need for robust and rigorous human in vivo testing-in particular, using refined seaweed extracts.

Vitamin D Biofortification of Pork May Offer a Food-Based Strategy to Increase Vitamin D Intakes in the UK Population.

Hypovitaminosis D is prevalent worldwide, with many populations failing to achieve the recommended nutrient intake (RNI) for vitamin D (10-20 µg/day). Owing to low vitamin D intakes, limited exposure to ultraviolet-B (UVB) induced dermal synthesis, lack of mandatory fortification and poor uptake in supplement advice, additional food-based strategies are warranted to enable the UK population to achieve optimal vitamin D intakes, thus reducing musculoskeletal risks or suboptimal immune functioning. The aims of the current study were to (1) determine any changes to vitamin D intake and status over a 9-year period, and (2) apply dietary modeling to predict the impact of vitamin D biofortification of pork and pork products on population intakes. Data from the UK National Diet and Nutrition Survey (Year 1-9; 2008/09-2016/17) were analyzed to explore nationally representative mean vitamin D intakes and 25-hydroxyvitamin D (25(OH)D) concentrations (n = 13,350). Four theoretical dietary scenarios of vitamin D pork biofortification were computed (vitamin D content +50/100/150/200% vs. standard). Vitamin D intake in the UK population has not changed significantly from 2008 to 2017 and in 2016/17, across all age groups, 13.2% were considered deficient [25(OH)D <25 nmol/L]. Theoretically, increasing vitamin D concentrations in biofortified pork by 50, 100, 150, and 200%, would increase vitamin population D intake by 4.9, 10.1, 15.0, and 19.8% respectively. When specifically considering the impact on gender and age, based on the last scenario, a greater relative change was observed in males (22.6%) vs. females (17.8%). The greatest relative change was observed amongst 11-18 year olds (25.2%). Vitamin D intakes have remained stable in the UK for almost a decade, confirming that strategies are urgently required to help the population achieve the RNI for vitamin D. Biofortification of pork meat provides a proof of concept, demonstrating that animal-based strategies may offer an important contribution to help to improve the vitamin D intakes of the UK population, particularly adolescents.

Ex vivo fecal fermentation of human ileal fluid collected after raspberry consumption modifies (poly)phenolics and modulates genoprotective effects in colonic epithelial cells.

Diets rich in fruit and vegetables are associated with a decreased incidence of colorectal cancer (CRC) due, in part, to the bioactive (poly)phenolic components and their microbiota-mediated metabolites. This study investigated how such compounds, derived from ingested raspberries in the gastrointestinal tract, may exert protective effects by reducing DNA damage. Ileal fluids collected pre- and post-consumption of 300 g of raspberries by ileostomists (n = 11) were subjected to 24 h ex vivo fermentation with fecal inoculum to simulate interaction with colonic microbiota. The impact of fermentation on (poly)phenolics in ileal fluid was determined and the bioactivity of ileal fluids pre- and post fermentation investigated. (Poly)phenolic compounds including sanguiin H-6, sanguiin H-10 and cyanidin-3-O-sophoroside decreased significantly during fermentation while, in contrast, microbial catabolites, including 3-(3'-hydroxyphenyl)propanoic acid, 3-hydroxybenzoic acid and benzoic acid increased significantly. The post-raspberry ileal fermentate from 9 of the 11 ileostomates significantly decreased DNA damage (~30%) in the CCD 841 CoN normal cell line using an oxidative challenge COMET assay. The raspberry ileal fermentates also modulated gene expression of the nuclear factor 2-antioxidant responsive element (Nrf2-ARE) pathway involved in oxidative stress cytoprotection, namely Nrf2, NAD(P)H dehydrogenase, quinone-1 and heme oxygenase-1. Four of the phenolic catabolites were assessed individually, each significantly reducing DNA damage from an oxidative challenge over a physiologically relevant 10-100 µM range. They also induced a differential pattern of expression of key genes in the Nrf2-ARE pathway in CCD 841 CoN cells. The study indicates that the colon-available raspberry (poly)phenols and their microbial-derived catabolites may play a role in protection against CRC in vivo.

Sulforaphane-enriched extracts from glucoraphanin-rich broccoli exert antimicrobial activity against gut pathogens in vitro and innovative cooking methods increase in vivo intestinal delivery of sulforaphane.

PURPOSE: Studies on broccoli (Brassica oleracea var. italica) indicate beneficial effects against a range of chronic diseases, commonly attributed to their bioactive phytochemicals. Sulforaphane, the bioactive form of glucoraphanin, is formed by the action of the indigenous enzyme myrosinase. This study explored the role that digestion and cooking practices play in bioactivity and bioavailability, especially the rarely considered dose delivered to the colon. METHODS: The antimicrobial activity of sulforaphane extracts from raw, cooked broccoli and cooked broccoli plus mustard seeds (as a source myrosinase) was assessed. The persistence of broccoli phytochemicals in the upper gastrointestinal tract was analysed in the ileal fluid of 11 ileostomates fed, in a cross-over design, broccoli soup prepared with and without mustard seeds. RESULTS: The raw broccoli had no antimicrobial activity, except against Bacillus cereus, but cooked broccoli (with and without mustard seeds) showed considerable antimicrobial activity against various tested pathogens. The recovery of sulforaphane in ileal fluids post soup consumption was < 1% but the addition of mustard seeds increased colon-available sulforaphane sixfold. However, when sulforaphane was extracted from the ileal fluid with the highest sulforaphane content and tested against Escherichia coli K12, no inhibitory effects were observed. Analysis of glucosinolates composition in ileal fluids revealed noticeable inter-individual differences, with six "responding" participants showing increases in glucosinolates after broccoli soup consumption. CONCLUSIONS: Sulforaphane-rich broccoli extracts caused potent antimicrobial effects in vitro, and the consumption of sulforaphane-enriched broccoli soup may inhibit bacterial growth in the stomach and upper small intestine, but not in the terminal ileum or the colon.

Endocannabinoids, endocannabinoid-like molecules and their precursors in human small intestinal lumen and plasma: does diet affect them?

PURPOSE: To determine the small intestinal concentration of endocannabinoids (ECs), N-acylethanolamines (NAEs) and their precursors N-acylphosphatidylethanolamines (NAPEs) in humans. To identify relationships between those concentrations and habitual diet composition as well as individual inflammatory status. METHODS: An observational study was performed involving 35 participants with an ileostomy (18W/17M, aged 18-70 years, BMI 17-40 kg/m2). Overnight fasting samples of ileal fluid and plasma were collected and ECs, NAEs and NAPEs concentrations were determined by LC-HRMS. Dietary data were estimated from self-reported 4-day food diaries. RESULTS: Regarding ECs, N-arachidonoylethanolamide (AEA) was not detected in ileal fluids while 2-arachidonoylglycerol (2-AG) was identified in samples from two participants with a maximum concentration of 129.3 µg/mL. In contrast, mean plasma concentration of AEA was 2.1 ± 0.06 ng/mL and 2-AG was 4.9 ± 1.05 ng/mL. NAEs concentrations were in the range 0.72-17.6 µg/mL in ileal fluids and 0.014-0.039 µg/mL in plasma. NAPEs concentrations were in the range 0.3-71.5 µg/mL in ileal fluids and 0.19-1.24 µg/mL in plasma being more abundant in participants with obesity than normal weight and overweight. Significant correlations between the concentrations of AEA, OEA and LEA in biological fluids with habitual energy or fat intakes were identified. Plasma PEA positively correlated with serum C-reactive protein. CONCLUSION: We quantified ECs, NAEs and NAPEs in the intestinal lumen. Fat and energy intake may influence plasma and intestinal concentrations of these compounds. The luminal concentrations reported would allow modulation of the homeostatic control of food intake via activation of GPR119 receptors located on the gastro-intestinal mucosa. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: NCT04143139; www.clinicaltrials.gov .

Aryl hydrocarbon Receptor activation during in vitro and in vivo digestion of raw and cooked broccoli (brassica oleracea var. Italica).

Broccoli is rich in glucosinolates, which can be converted upon chewing and processing into Aryl hydrocarbon Receptor (AhR) ligands. Activation of AhR plays an important role in overall gut homeostasis but the role of broccoli processing on the generation of AhR ligands is still largely unknown. In this study, the effects of temperature, cooking method (steaming versus boiling), gastric pH and further digestion of broccoli on AhR activation were investigated in vitro and in ileostomy subjects. For the in vitro study, raw, steamed (t = 3 min and t = 6 min) and boiled (t = 3 min and t = 6 min) broccoli were digested in vitro with different gastric pH. In the in vivo ileostomy study, 8 subjects received a broccoli soup or a broccoli soup plus an exogenous myrosinase source. AhR activation was measured in both in vitro and in vivo samples by using HepG2-Lucia™ AhR reporter cells. Cooking broccoli reduced the AhR activation measured after gastric digestion in vitro, but no effect of gastric pH was found. Indole AhR ligands were not detected or detected at very low levels both after intestinal in vitro digestion and in the ileostomy patient samples, which resulted in no AhR activation. This suggests that the evaluation of the relevance of glucosinolates for AhR modulation in the gut cannot prescind from the way broccoli is processed, and that broccoli consumption does not necessarily produce substantial amounts of AhR ligands in the large intestine.

Modest improvement in CVD risk markers in older adults following quinoa (Chenopodium quinoa Willd.) consumption: a randomized-controlled crossover study with a novel food product.

PURPOSE: To investigate the effect of consuming quinoa biscuits on markers of CVD risk over 4 weeks in free-living older adults. METHODS: A randomized-controlled, double-blind crossover trial was conducted in which consenting healthy adults aged 50-75 years (n = 40) consumed 15 g quinoa biscuits (60 g quinoa flour/100 g) or control iso-energetic biscuits (made using wheat flour) daily for 28 consecutive days (4 weeks), in addition to their normal diet. Following a 6-week washout, participants consumed the alternate biscuit for a final 4 weeks. Anthropometry and fasted blood samples were obtained before and after each intervention period. RESULTS: At the beginning of the trial, mean ± SD total cholesterol concentrations were 6.02 ± 1.22 mmol/L (3.7-9.2 mmol/L); 33 participants (82.5%) had high cholesterol (> 5 mmol/L). No participants were lost to follow-up and there were no changes in habitual dietary intakes or levels of physical activity between each 4-week intervention period. Significantly greater decreases in total and LDL cholesterol concentrations (- 0.30 ± 0.58 and - 0.25 ± 0.38 mmol/L, respectively), TC: HDL ratio (- 0.11 ± 0.30), weight (- 0.61 ± 0.89 kg) and BMI (- 0.22 ± 0.34 kg/m2) were apparent following consumption of the quinoa versus control biscuits (all P < 0.05). Changes in triglycerides, HDL cholesterol, or PUFA or CRP concentrations were not significant between treatment groups. CONCLUSION: Consumption of novel quinoa biscuits produced small, but favorable changes in body weight, BMI, and circulating cholesterol concentrations, all of which may contribute to lowered CVD risk in older adults.

Antioxidant and antigenotoxic activities of Ginkgo biloba L. leaf extract are retained after in vitro gastrointestinal digestive conditions.

PURPOSE: The recognized biological properties of Ginkgo biloba extracts potentiate their utilization as an ingredient for functional foods. However, the digestive conditions can affect the chemical composition of the extracts and consequently their biological properties, which can lead to food safety problems. Thus, the impact of in vitro-simulated upper gastrointestinal tract digestion on the chemical composition and bioactivity of Ginkgo biloba leaf extract (GBE) was evaluated. METHODS: Physicochemical conditions of human digestion were simulated in vitro, and its impact on the chemical composition of GBE was investigated by electrospray ionization-mass spectrometry. The persistence of bioactivity was investigated by subjecting GBE and the in vitro digested extract (DGBE) to the same methodology. Antioxidant properties were assessed using 2',7'-dichlorofluorescein diacetate to measure the intracellular oxidation of Schizosaccharomyces pombe cells pre-incubated with GBE or DGBE and exposed to H2O2. Antigenotoxicity was tested by comet assay in HT-29 colon cancer cells pre-incubated with GBE or DGBE and challenged with H2O2. RESULTS: The chemical analysis revealed a considerable change in chemical composition upon digestion. Pre-incubation with GBE or DGBE attenuated the H2O2-imposed intracellular oxidation in wild-type S. pombe cells, unlike the oxidative stress response-affected mutants sty1 and pap1, and decreased H2O2-induced DNA damage in HT-29 cells. The extracts did not induce toxicity in these eukaryotic models. CONCLUSION: The chemical composition of GBE was affected by in vitro digestion, but the antioxidant and antigenotoxic activities persisted. Therefore, G. biloba extract may be suitable for use as food additive and contribute to a healthy colon.

Digestion and Colonic Fermentation of Raw and Cooked Opuntia ficus-indica Cladodes Impacts Bioaccessibility and Bioactivity.

The bioactivity of (poly)phenols from a food is an interplay between the cooking methods applied and the interaction of the food with the gastrointestinal tract. The (poly)phenolic profile and biological activity of raw and cooked cactus ( Opuntia ficus-indica Mill.) cladodes following in vitro digestion and colonic fermentation were evaluated. Twenty-seven (poly)phenols were identified and quantified by HPLC-ESI-MS, with piscidic acid being the most abundant. Throughout the colonic fermentation, flavonoids showed more degradation than phenolic acids, and eucomic acid remained the most relevant after 24 h. The catabolite 3-(4-hydroxyphenyl)propionic acid was generated after 24 h of fermentation. Cytotoxicity, genotoxicity, and cell cycle analyses were performed in HT29 cells. Cactus colonic fermentates showed higher cell viability (≥80%) in comparison to the control fermentation with no cactus and significantly ( p < 0.05) reduced H2O2-induced DNA damage in HT29 cells. Results suggest that, although phenolic compounds were degraded during the colonic fermentation, the biological activity is retained in colon cells.

Phenyl-γ-valerolactones and phenylvaleric acids, the main colonic metabolites of flavan-3-ols: synthesis, analysis, bioavailability, and bioactivity.

Covering: 1958 to June 2018 Phenyl-γ-valerolactones (PVLs) and their related phenylvaleric acids (PVAs) are the main metabolites of flavan-3-ols, the major class of flavonoids in the human diet. Despite their presumed importance, these gut microbiota-derived compounds have, to date, in terms of biological activity, been considered subordinate to their parent dietary compounds, the flavan-3-ol monomers and proanthocyanidins. In this review, the role and prospects of PVLs and PVAs as key metabolites in the understanding of the health features of flavan-3-ols have been critically assessed. Among the topics covered, are proposals for a standardised nomenclature for PVLs and PVAs. The formation, bioavailability and pharmacokinetics of PVLs and PVAs from different types of flavan-3-ols are discussed, taking into account in vitro and animal studies, as well as inter-individual differences and the existence of putative flavan-3-ol metabotypes. Synthetic strategies used for the preparation of PVLs are considered and the methodologies for their identification and quantification assessed. Metabolomic approaches unravelling the role of PVLs and PVAs as biomarkers of intake are also described. Finally, the biological activity of these microbial catabolites in different experimental models is summarised. Knowledge gaps and future research are considered in this key area of dietary (poly)phenol research.