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Introduction: The gut microbiota has emerged as a key factor on one hand as a mediator of the effects of diet on health and, on the other hand, as a source of intervariability of response to a diet. Moreover, there is a strong bidirectional interaction between our health and the microbiota that inhabit us, with each determining the presence of the other. In this review are named some of the metabolic functions in which the microbiota participates and which have an impact on our health, with particular emphasis on its ability to ferment fiber and produce short-chain fatty acids (SCFA) that provide numerous benefits to our health, but which have also been linked to obesity. Finally, some examples of dietary intervention in which the microbiota has been shown to play a key role in the results obtained are mentioned. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin D is a key nutrient for health. Recent research has shown that it is not only necessary for the maintenance of bone health, but also for the prevention of cardiovascular diseases, insulin resistance, respiratory diseases, infections, and cancer, among others. Solar synthesis of vitamin D is usually insufficient, so it is necessary to provide enough vitamin D through the diet in order to maintain an adequate nutritional status. Studies carried out in Spain and other countries have shown that serum levels of the vitamin were usually insufficient and that average dietary intakes were well below those marked as recommended, while the main food sources of vitamin D were fatty fish, breakfast cereals, eggs, and dairy. Food sources of vitamin D are scarce, and it is naturally located in the fatty part of foods of animal origin, and in the liver and viscera. Fortifying foods that are not natural food sources of vitamin D but are regularly consumed by a significant percentage of the population, is a strategy that could help to increase vitamin D intake. In this regard, dairy products and breakfast cereals are two of the most widely used food matrices for vitamin D fortification, and their incorporation into the usual diet has proven to be an effective strategy to improve the nutritional situation of the population in vitamin D. [ABSTRACT FROM AUTHOR]

Exercising is one of the greatest benefits for the health. However, at a systemic level it can be harmful depending on the intensity degree with which the athletes practice. The high-resistance training involves exhaustive training that can result in gastrointestinal symptoms and systemic manifestations occur such as the triggering of the inflammatory process, progression of oxidative stress and gut microbiota modification. Currently, athletes consume commercial products to counteract these effects. However, there are natural therapeutic alternatives such as the consumption of sources rich in dietary fiber and polyphenols. The use of these sources can improve the symptoms presented by reducing systemic oxidative processes, improving intestinal protection and increasing sports performance. This review it focuses on the systemic mechanisms modifiable by the high-resistance training and the consumption of natural sources as fiber and polyphenolic compounds a therapeutic alternative to reduce intestinal symptoms and negative systemic processes in the athlete and favor naturally their gut health. [ABSTRACT FROM AUTHOR]

Purpose: The impact of ingesting carbohydrates alone or combined with proteins to support exercise immune adaptation in endurance athletes is scarcely investigated. The present study compares the effect of ingesting a combined protein–carbohydrate supplement vs. a carbohydrate-only supplement post-workout on immune inflammation markers following a 10 week periodized endurance training program in well-trained athletes. Methods: Twenty-five men completed the study after being randomly assigned to one of the following intervention groups: combined protein–carbohydrate (PRO-CHO n = 12, 31 ± 9 years, V ˙ O2peak 61.0 ± 5.6 ml.kg−1.min−1) or non-protein isoenergetic carbohydrate (CHO, n = 13, 33 ± 8 years, V ˙ O2peak 60.6 ± 6.9 ml.kg−1.min−1). Treatment consisted of ingesting 24 g of assigned supplement, mixed with 250 ml of orange juice, once a day for 10 weeks immediately post-workout (or before breakfast on non-training days). Measurements were conducted pre- and post-intervention on total leukocytes, leukocyte subsets (i.e., neutrophils, eosinophils, basophils, monocytes, and lymphocytes), and platelets. The inflammatory status was assessed by the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the systemic-immune inflammation index (SII). Results: Post-intervention, significant increases were observed for CHO group only for the three inflammatory markers: NLR (p = 0.050, d = 0.58), PLR (p = 0.041, d = 0.60), and SII (p = 0.004, d = 0.81) but not for PRO-CHO (p > 0.05). Conclusion: Ingesting a post-workout protein–carbohydrate combined beverage promoted a more favourable immune status than carbohydrate-only ingestion by attenuating cellular inflammation over a 10 week training period in endurance male athletes. Trial Registration: The study was registered in ClinicalTrials.gov with the following ID: NCT02954367. The study was registered by 3 November 2016. [ABSTRACT FROM AUTHOR]

Traditionally, plant food extracts and phytochemical compounds have been used as remedies against microbial infections with the added benefit that most of them are safe for human consumption. These compounds have been also highlighted as Quorum Sensing Inhibitors (QSI). Quorum Sensing (QS) is a regulatory mechanism that enables bacteria to make collective decisions with respect to the expression of a specific set of genes which can be related to virulence factors. Among all the available studies, most of them use biosensor to demonstrate the role of plant foods and phytochemicals as QSI and only few of these studies focus on their mechanisms of action. This review summarizes the published scientific work on the use of plant food extracts and phytochemicals as QSI, highlighting the techniques used to identify their biological activity and their mechanisms of action. [ABSTRACT FROM AUTHOR]

The impact of animal protein blend supplements in endurance athletes is scarcely researched. The authors investigated the effect of ingesting an admixture providing orange juice and protein (PRO) from beef and whey versus carbohydrate alone on body composition and performance over a 10-week training period in male endurance athletes. Participants were randomly assigned to a protein (CHO + PRO, n = 15) or a nonprotein isoenergetic carbohydrate (CHO, n = 15) group. Twenty grams of supplement mixed with orange juice was ingested postworkout or before breakfast on nontraining days. Measurements were performed pre- and postintervention on body composition (by dual-energy X-ray absorptiometry), peak oxygen consumption (...O2peak), and maximal aerobic speed. Twenty-five participants (CHO + PRO, n = 12; CHO, n = 13) completed the study. Only the CHO + PRO group significantly (p < .05) reduced whole-body fat (mean ± SD) (-1.02 ± 0.6 kg), total trunk fat (-0.81 ± 0.9 kg), and increased total lower body lean mass (+0.52 ± 0.7 kg), showing close to statistically significant increases of whole-body lean mass (+0.57 ± 0.8 kg, p = .055). Both groups reduced (p < .05) visceral fat (CHO + PRO, -0.03 ± 0.1 kg; CHO, -0.03 ± 0.5 kg) and improved the speed at maximal aerobic speed (CHO + PRO, +0.56 ± 0.5 km/hr; CHO, +0.35 ± 0.5 km/hr). Although consuming animal protein blend mixed with orange juice over 10 weeks helped to reduce fat mass and to increase lean mass, no additional performance benefits in endurance runners were observed. [ABSTRACT FROM AUTHOR]

Abstract: In the last decades nutraceuticals have entered the health market as an easy and attractive means of preventing diseases. These products are of interest for an increasingly health-concerned society and may be especially relevant for preventing or delaying a number of age-related diseases, i.e. arthritis, cancer, metabolic and cardiovascular diseases, osteoporosis, cataracts, brain disorders, etc. Nutraceuticals are marketed in a variety of forms, composition and potential applications which have made their definition ambiguous and their use uncontrolled and poorly funded. Although epidemiological, animal and in vitro studies have given evidence of the potential benefits of some of these nutraceuticals or of their components, definitive proof of their effects in appropriate human clinical trials is still lacking in most cases, more critically among people above 65 years of age. We cover the well-established nutraceuticals (polyvitamins, omega-3 fatty acids, etc.) and will focus on many other ‘novel’ commercial nutraceuticals where the scientific evidence is more limited (food extracts, polyphenols, carotenoids, etc.). Solid scientific evidence has been reported only for a few nutraceuticals, which have some health claims approved by the European Food Safety Authority (EFSA). Further well-designed trials are needed to improve the current knowledge on the health benefits of nutraceuticals in the elderly. Overall, there are some facts, a lot of fiction and many gaps in the knowledge of nutraceutical benefits. [Copyright &y& Elsevier]

Abstract: Numerous studies have shown that resveratrol (RES) exerts anti-inflammatory effects but human trials evidencing these effects in vivo are limited. Furthermore, the molecular mechanisms triggered in humans following the oral intake of RES are not yet understood. Therefore, the purpose of this study was to investigate the molecular changes in peripheral blood mononuclear cells (PBMCs) associated to the one-year daily intake of a RES enriched (8mg) grape extract (GE-RES) in hypertensive male patients with type 2 diabetes mellitus (T2DM). We used microarrays and RT-PCR to analyze expression changes in genes and microRNAs (miRs) involved in the inflammatory response modulated by the consumption of GE-RES in comparison to a placebo and GE lacking RES. We also examined the changes in several serobiochemical variables, inflammatory and fibrinolytic markers. Our results showed that supplementation with GE or GE-RES did not affect body weight, blood pressure, glucose, HbA1c or lipids, beyond the values regulated by gold standard medication in these patients. We did not find either any significant change on serum inflammatory markers except for a significant reduction of ALP and IL-6 levels. The expression of the pro-inflammatory cytokines CCL3, IL-1β and TNF-α was significantly reduced and that of the transcriptional repressor LRRFIP-1 increased in PBMCs from patients taking the GE-RES extract. Also, a group of miRs involved in the regulation of the inflammatory response: miR-21, miR-181b, miR-663, miR-30c2, miR-155 and miR-34a were found to be highly correlated and altered in the group consuming the GE-RES for 12 months. Our results provide preliminary evidence that long-term supplementation with a grape extract containing RES downregulates the expression of key pro-inflammatory cytokines with the involvement of inflammation-related miRs in circulating immune cells of T2DM hypertensive medicated patients and support a beneficial immunomodulatory effect in these patients. [Copyright &y& Elsevier]

The health benefits attributed to pomegranate have been associated with its high content in polyphenols, particularly ellagitannins. This is also the case for other ellagitannin-containing fruits and nuts including strawberry, raspberry, blackberry, walnuts, and muscadine grapes. The bioavailability of ellagitannins and ellagic acid is however very low. These molecules suffer extensive metabolism by the gut microbiota to produce urolithins that are much better absorbed. Urolithins circulate in plasma as glucuronide and sulfate conjugates at concentrations in the range of 0.2-20 ΜM. It is therefore conceivable that the health effects of ellagitannin-containing products can be associated with these gut-produced urolithins, and thus the evaluation of the biological effects of these metabolites is essential. Recent research, mostly based on in vitro testing, has shown preliminary evidence of the anti-inflammatory, anticarcinogenic, antiglycative, antioxidant, and antimicrobial effects of urolithins, supporting their potential contribution to the health effects attributed to pomegranate and ellagitannin-rich foods. The number of in vivo studies is still limited, but they show preventive effects of urolithins on gut and systemic inflammation that encourage further research. Both in vivo and mechanistic studies are necessary to clarify the health effects of these metabolites. Attention should be paid when designing these mechanistic studies in order to use the physiologically relevant metabolites (urolithins in gut models and their conjugated derivatives in systemic models) at concentrations that can be reached in vivo. [ABSTRACT FROM AUTHOR]

Abstract: Pseudomonas aeruginosa is an aerobic Gram-negative bacterium characterized by a natural resistance to several antibiotics. It is a major cause of nosocomial infections in patients with compromised host defence mechanisms mainly related to the respiratory tract. P. aeruginosa infection first step is the adhesion of the bacteria to the host cells and thus, the development of techniques that can easily assess adhesion of bacteria strains and of bacteria isolated from biological samples is fundamental. The aim of our work was to develop a fast and effective method to evaluate the adhesion of P. aeruginosa to bronchial epithelial cells. To meet our goal we optimized a staining protocol using the vital dye SYTO 9 and P. aeruginosa PAO1. We established the appropriate dying conditions as well as the stability of the stained bacteria. Adhesion was first measured using the traditional plate counting method and then, adhesion values were compared to those obtained using a fluorescence microplate reader and epifluorescence microscopy. Our results show that the use of SYTO 9 does not interfere with the bacteria viability, bacteria cell growth, and adhesion of P. aeruginosa to A549 epithelial cells. Both the fluorescence microplate reader and the epifluorescence microscopy gave similar results to those attained with the plate counting method, however, the epifluorescence microscopy also allowed for simultaneous discrimination of damaging effects on the human cells. Overall, our data indicate that the use of SYTO 9 combined with a fluorescence microplate reader or an epifluorescence microscope provides a rapid method to evaluate the adhesion of P. aeruginosa to human epithelial cells. However, to show unequivocally that a specific drug or compound has a truly inhibitory effect on the bacterial adhesion without affecting the number of human cells, the epifluorescence microscopy is recommended. [Copyright &y& Elsevier]

Abstract: Hydrolysable tannins are phenolic phytochemicals that show high antioxidant and free-radical scavenging activities. For this reason their potential effects preventing oxidative related diseases, such as cardiovascular diseases, have been largely studied. In vitro studies show that ellagitannins, at concentrations in the range 10–100μM, show some relevant anti-atherogenic, anti-thrombotic, anti-inflammatory and anti-angiogenic effects, supporting the molecular mechanisms for the vascular health benefits. While there is good evidence supporting the vascular effects in vitro, the evidence on animal models or humans is much scarcer. The in vitro results often do not match the findings in the in vivo studies. This could be explained by the low bioavailability of the antioxidant ellagitannins and ellagic acid. The main ellagitannin metabolites circulating in plasma are ellagic acid microbiota metabolites known as urolithins, and they have lost their free-radical scavenging activity. They are present in plasma as glucuronide or sulphate conjugates, at concentrations in the nM range. Future studies should focus in the bioavailable metabolites, urolithins, and in the form (conjugated with glucuronic acid or sulphate) and concentrations (nM range) in which they are found in plasma. In this review we critically discuss the role of ellagitannins and ellagic acid on vascular health. [ABSTRACT FROM AUTHOR]

Whether the beneficial effects of pomegranate are due to the ellagitannins or to their microbiota-derived urolithins is not known. Our objectives were to evaluate the effects of pomegranate intake and its main microbiota-derived metabolite urolithin-A (UROA) on colon inflammation and to assess whether UROA is the main anti-inflammatory compound. In addition, the effect of the inflammation on the phenolic metabolism was also explored. Male Fisher rats were fed with 250 mg kg−1 day−1 pomegranate extract (PE) or 15 mg kg−1 day−1 UROA for 25 days. Dextran sodium sulfate (5%) (DSS) was administered for the five last days and then rats were euthanized. DSS is a well-known model of inflammatory bowel disease. Colon tissue damage, microbiota changes, antioxidant status, prostaglandin E2 (PGE2), nitric oxide production, inducible nitric oxide synthase (iNOS), prostaglandin E synthase (PTGES), gene expression (microarrays and RT-PCR) and polyphenol metabolism (LC-MS-MS) were evaluated. Both PE and UROA decreased inflammation markers (iNOS, cycloxygenase-2, PTGES and PGE2 in colonic mucosa) and modulated favorably the gut microbiota. The G1 to S cell cycle pathway was up-regulated in both groups. UROA group showed various down-regulated pathways, including that of the inflammatory response. PE, but not UROA, decreased oxidative stress in plasma and colon mucosa. Only UROA preserved colonic architecture. The normal formation of urolithins in PE-fed rats was prevented during inflammation. Our results suggest that UROA could be the most active anti-inflammatory compound derived from pomegranate ingestion in healthy subjects, whereas in colon inflammation, the effects could be due to the nonmetabolized ellagitannin-related fraction. [Copyright &y& Elsevier]

This paper studied the effect on UV-B ocular damage of 10µm hydrocaffeic acid (HCAF) alone and as a mixture (MIX) (5µm HCAF+5µm p-coumaric acid). Since ocular UV-B damage is mediated by reactive oxygen species, the aim was to test if HCAF and MIX could reduce oxidation damage in human conjunctival cells (WKD) in vitro and in cornea and sclera of rabbits in vivo. After UVB irradiation (44 J/m2) of WKD cells, 8-oxodG levels in DNA were markedly increased and this effect was attenuated by HCAF and MIX. Rabbit eyes were treated by application of HCAF and MIX drops before UV-B exposure (79 J/m2). Corneal and scleral DNA oxidation damage, xanthine-oxidase (XO) activity and malondialdehyde levels (MDA) in corneal tissue and prostaglandin E2 (PGE2) in the aqueous humour were reduced by HCAF alone and in combination with p-coumaric acid, showing their potential as a topical treatment against UV-B damage. [ABSTRACT FROM AUTHOR]

Abstract: Consumption of berries and red fruits rich in polyphenols may contribute to the reduction of colon cancer through mechanisms not yet understood. In this study, we investigated the response of subconfluent Caco-2 cells (a human colon carcinoma model) to repetitive exposure (2 h a day for a 4-day period) of a subtoxic dose of a chokeberry (Aronia melanocarpa) juice containing mixed polyphenols. To mimic physiological conditions, we subjected the chokeberry juice to in vitro gastric and pancreatic digestion. The effects on viability, proliferation and cell cycle were determined, and changes in the expression of genes in response to the chokeberry treatment were screened using Affymetrix oligonucleotide microarrays. Exposure to the chokeberry juice inhibited Caco-2 cell proliferation by causing G2/M cell cycle arrest. We detected changes in the expression of a group of genes involved in cell growth and proliferation and cell cycle regulation, as well as those associated to colorectal cancer. A selection of these genes was further confirmed by quantitative RT-PCR. Among these, the tumor suppressor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), whose expression is known to be reduced in the majority of early adenomas and carcinomas, was up-regulated by the treatment both at the mRNA and protein levels (as shown by flow cytometry analysis). CEACAM1, with a significant regulatory role on cell proliferation of particular interest at early stages of cancer development, may be a potential target for chemoprevention by food components such as those present in polyphenol-rich fruits. [Copyright &y& Elsevier]

Abstract: Polyphenol-rich dietary foodstuffs have attracted attention due to their cancer chemopreventive and chemotherapeutic properties. Ellagitannins (ETs) belong to the so-called hydrolysable tannins found in strawberries, raspberries, walnuts, pomegranate, oak-aged red wine, etc. Both ETs and their hydrolysis product, ellagic acid (EA), have been reported to induce apoptosis in tumour cells. Ellagitannins are not absorbed in vivo but reach the colon and release EA that is metabolised by the human microflora. Our aim was to investigate the effect of a dietary ET [pomegranate punicalagin (PUNI)] and EA on human colon cancer Caco-2 and colon normal CCD-112CoN cells. Both PUNI and EA provoked the same effects on Caco-2 cells: down-regulation of cyclins A and B1 and upregulation of cyclin E, cell-cycle arrest in S phase, induction of apoptosis via intrinsic pathway (FAS-independent, caspase 8-independent) through bcl-XL down-regulation with mitochondrial release of cytochrome c into the cytosol, activation of initiator caspase 9 and effector caspase 3. Neither EA nor PUNI induced apoptosis in normal colon CCD-112CoN cells (no chromatin condensation and no activation of caspases 3 and 9 were detected). In the case of Caco-2 cells, no specific effect can be attributed to PUNI since it was hydrolysed in the medium to yield EA, which entered into the cells and was metabolised to produce dimethyl-EA derivatives. Our study suggests that the anticarcinogenic effect of dietary ETs could be mainly due to their hydrolysis product, EA, which induced apoptosis via mitochondrial pathway in colon cancer Caco-2 cells but not in normal colon cells. [Copyright &y& Elsevier]

The article presents a discussion on antimelanoma effect of Piceatannol on human melanoma cells. Piceatannol is a polyphenol present in grapes and wine. Piceatannol has been reported to be a protein-tyrosine kinase inhibitor with immuno-suppressive activity, which could be important for preventing graft rejection. In a study presented in the article, human SK-Mel-28 melanoma cells were incubated with piceatannol for 72 hours. Cell cycle and viability were examined using flow cytometry analysis. The antimelanoma properties of dietary piceatannol cannot be ruled out taking into account its fast and potent pro-apoptotic capacity at low concentration.

Phenolic-enriched extracts from blanched artichoke (BA), artichoke blanching waters (ABW), cauliflower (CA), carrot (CR), celery (CE) and onion (ON) byproducts were used to ‘functionalise’ tomato juice. The antioxidant activity of functional tomato juice significantly increased over control juice according to a set of in vitro antioxidant assays (i.e. inhibition of lipid peroxidation determined by the ferric thiocyanate method and scavenging of both ABTS•+ and DPPH• free radicals). A trained sensory evaluation panel determined the maximal allowed byproduct extract concentration in the functionalisation of tomato juice without modifying its natural sensory properties (mg extract/mL tomato juice): 2.5, 5, 10, 10, 10 and 20 for CA, ON, BA, ABW, CE and CR, respectively. The maximum antioxidant activity (within consumers'' acceptance limits and measured by the ABTS•+ method) was increased 5.4-, 3.4-, 2.5-, 1.7-, 1.5- and 0.6-fold over the control when functional tomato juice was assayed after modification with ABW, BA, CR, ON, CE and CA, respectively. A serving of functional tomato juice (250 mL) containing vegetable extracts (within consumers'' acceptance limits) provides an additional intake of phenolic compounds which can range from 22 mg (when functionalised with CA extract) to 300 mg (with BA extract). In the light of the above investigations, the use of vegetable byproducts could be useful for developing a functional tomato juice with potentially increased health-promoting properties. [Copyright &y& Elsevier]

• Azithromycin preserves adult hippocampal neurogenesis in LPS-treated mice. • Azithromycin reduces time spent immobile by LPS-treated mice during the Porsolt test. • Azithromycin reverses the hippocampal pro-inflammatory phenotype caused by LPS. • Azithromycin promotes synaptic integration. The mammalian hippocampus can generate new neurons throughout life. Known as adult hippocampal neurogenesis (AHN), this process participates in learning, memory, mood regulation, and forgetting. The continuous incorporation of new neurons enhances the plasticity of the hippocampus and contributes to the cognitive reserve in aged individuals. However, the integrity of AHN is targeted by numerous pathological conditions, including neurodegenerative diseases and sustained inflammation. In this regard, the latter causes cognitive decline, mood alterations, and multiple AHN impairments. In fact, the systemic administration of Lipopolysaccharide (LPS) from E. coli to mice (a model of sepsis) triggers depression-like behavior, impairs pattern separation, and decreases the survival, maturation, and synaptic integration of adult-born hippocampal dentate granule cells. Here we tested the capacity of the macrolide antibiotic azithromycin to neutralize the deleterious consequences of LPS administration in female C57BL6J mice. This antibiotic exerted potent neuroprotective effects. It reversed the increased immobility time during the Porsolt test, hippocampal secretion of pro-inflammatory cytokines, and AHN impairments. Moreover, azithromycin promoted the synaptic integration of adult-born neurons and functionally remodeled the gut microbiome. Therefore, our data point to azithromycin as a clinically relevant drug with the putative capacity to ameliorate the negative consequences of chronic inflammation by modulating AHN and hippocampal-related behaviors. [ABSTRACT FROM AUTHOR]

This study examined the association between genetic variations in the Vitamin D Receptor (VDR) gene and the composition of gut microbiota in a Spanish population. The VDR gene plays a role in mediating the effects of vitamin D on gut microbiota composition. We analyzed 87 healthy participants from the Spanish Caucasian population and found that the genetic variations were in Hardy–Weinberg equilibrium. Through metataxonomic sequencing, we identified that the GG genotype from the VDR polymorphism rs731236 seems to be associated with the opportunistic genus Solobacterium, indicating that genetic variations may influence the composition of gut microbiota. [ABSTRACT FROM AUTHOR]

Internal training load refers to the degree of disturbance in psychophysiological homeostasis provoked by a training session and has been traditionally measured through session-RPE, which is the product of the session Rate of Perceived Exertion (RPE) and the duration. External training load refers to the actual physical work completed, and depends on session volume, intensity, frequency and density. Drafting, which is achieved by running closely behind another runner has been demonstrated to reduce the energy cost of running at a fixed speed and to improve performance. Therefore, it is hypothesised that psychophysiological responses might reflect different levels of internal load if training is performed individually or collectively. 16 elite middle-distance runners performed two high-intensity training sessions consisting of 4 repetitions of 500 m separated by 3 min of passive recovery. Sessions were performed individually and collectively. Times for each repetition, RPE, core affect (valence and felt arousal) and blood lactate concentrations [BLa] were measured after each repetition. Main time effect was significant and increased across repetitions for [BLa] and RPE (p < 0.001), and decreased for valence (p = 0.001). Main group effect was significant and values were higher when training individually for [BLa] (p = 0.003) and RPE (p = 0.001), and lower for valence (p = 0.001). No differential responses were found between conditions in terms of repeat time or felt arousal. Findings demonstrate that elite middle-distance athletes running collectively display lower levels of internal training load compared to running alone, despite external training load being similar. [ABSTRACT FROM AUTHOR]

Plant-derived nanovesicles (PDNVs) have recently emerged as natural delivery systems of biofunctional compounds toward mammalian cells. Considering their already described composition, anti-inflammatory properties, stability, and low toxicity, PDNVs offer a promising path for developing new preventive strategies for several inflammatory diseases, among which the inflammatory bowel disease (IBD). In this study, we explore the protective effects of industrially produced lemon vesicles (iLNVs) in a rat model of IBD. Characterization of iLNVs reveals the presence of small particles less than 200 nm in size and a profile of bioactive compounds enriched in flavonoids and organic acids with known beneficial properties. In vitro studies on human macrophages confirm the safety and anti-inflammatory effects of iLNVs, as evidenced by the reduced expression of pro-inflammatory cytokines and increased levels of anti-inflammatory markers. As evidenced by in vivo experiments, pre-treatment with iLNVs significantly alleviates symptoms and histological features in 2,4 dinitrobenzensulfuric acid (DNBS)-induced colitis in rats. Molecular pathway analysis reveals modulation of NF-κB and Nrf2, indicating anti-inflammatory and antioxidant effects. Finally, iLNVs affects gut microbiota composition, improving the consistent colitis-related alterations. Overall, we demonstrated the protective role of industrially produced lemon nanovesicles against colitis and emphasized their potential in managing IBD through multifaceted mechanisms. [Display omitted] • Lemon nanovesicles (iLNVs) play a protective role against DNBS-induced colitis in rat. • iLNVs decrease colitis-associated inflammatory damages. • iLNVs restore the rat intestinal permeability acting on tight junctions. • iLNVs shape the gut microbiota. [ABSTRACT FROM AUTHOR]

Background: Carnosic acid (CA) and rosemary extracts (RE) show body-weight, energy metabolism and inflammation regulatory properties in animal models but the mechanisms are not yet understood. Gut microbiota plays an important role in the host metabolism and inflammatory status and is modulated by the diet. The aim of this research was to investigate whether a RE enriched in CA affected caecum microbiota composition and activity in a rat model of genetic obesity. Methods and Principal Findings: A RE (40% CA) was administered with the diet (0.5% w/w) to lean (fa/+) and obese (fa/fa) female Zucker rats for 64 days. Changes in the microbiota composition and β-glucosidase activity in the caecum and in the levels of macronutrients and short chain fatty acids (SCFA) in feces were examined. The RE increased the Blautia coccoides and Bacteroides/Prevotella groups and reduced the Lactobacillus/Leuconostoc/Pediococccus group in both types of animals. Clostridium leptum was significantly decreased and Bifidobacterium increased only in the lean rats. β-Glucosidase activity was significantly reduced and fecal fiber excretion increased in the two genotypes. The RE also increased the main SCFA excreted in the feces of the obese rats but decreased them in the lean rats reflecting important differences in the uptake and metabolism of these molecules between the two genotypes. Conclusions: Our results indicate that the consumption of a RE enriched in CA modifies microbiota composition and decreases β-glucosidase activity in the caecum of female Zucker rats while it increases fiber fecal elimination. These results may contribute to explain the body weight gain reducing effects of the RE. The mutated leptin receptor of the obese animals significantly affects the microbiota composition, the SCFA fecal excretion and the host response to the RE intake. [ABSTRACT FROM AUTHOR]

Post-exercise microcurrent based treatments have shown to optimise exercise-induced adaptations in athletes. We compared the effects of endurance training in combination with either, a microcurrent or a sham treatment, on endurance performance. Additionally, changes in body composition, post-exercise lactate kinetics and perceived delayed onset of muscle soreness (DOMS) were determined. Eighteen males (32.8 ± 6.3 years) completed an 8-week endurance training programme involving 5 to 6 workouts per week wearing a microcurrent (MIC, n=9) or a sham (SH, n=9) device for 3-h post-workout or in the morning during non-training days. Measurements were conducted at pre- and post-intervention. Compared to baseline, both groups increased (P < 0.01) maximal aerobic speed (MIC, pre = 17.6 ± 1.3 to post=18.3 ± 1.0; SH, pre=17.8 ± 1.5 to post = 18.3 ± 1.3 km.h−1) with no changes in V ˙ O2peak. No interaction effect per group and time was observed (P=0.193). Although both groups increased (P < 0.05) trunk lean mass (MIC, pre=23.2 ± 2.7 to post=24.2 ± 2.0; SH, pre=23.4 ± 1.7 to post=24.3 ± 1.6 kg) only MIC decreased (pre=4.8 ± 1.5 to post=4.5 ± 1.5, p=0.029) lower body fat. At post-intervention, no main differences between groups were observed for lactate kinetics over the 5 min recovery period. Only MIC decreased (P<0.05) DOMS at 24-h and 48-h, showing a significant average lower DOMS score over 72-h after the completion of the exercise-induced muscle soreness protocol. In conclusion, a 3-h daily application of microcurrent over an 8-week endurance training programme produced no further benefits on performance in endurance-trained males. Nonetheless, the post-workout microcurrent application promoted more desirable changes in body composition and attenuated the perception of DOMS over 72-h post-exercise. [ABSTRACT FROM AUTHOR]

Primary prevention of cardiovascular disease (CVD) aims to avoid a first event in subjects that are at risk but have not yet been diagnosed with heart disease. Secondary prevention of CVD aims to avoid new events in patients with established heart disease. Both approaches involve clinical intervention and implementation of healthy lifestyles. The grape and wine polyphenol resveratrol (3,5,4′-trihydroxy- trans-stilbene) has shown cardioprotective benefits in humans. Most of these approaches deal with rather high doses and short follow-ups, and do not address the issue of long-term resveratrol consumption safety, especially in medicated individuals. Here, we review the trials conducted with resveratrol in patients at risk for or with established CVD, focusing on the two longest human clinical trials reported so far (1-year follow-up). We also discuss the expectations for resveratrol from a dietary and clinical perspective in relation to CVD. However, statistically significant changes in CVD-risk markers do not necessarily equal clinical significance in the daily care of patients. [ABSTRACT FROM AUTHOR]

The search for complementary treatments in primary prevention of cardiovascular disease (CVD) is a high-priority challenge. Grape and wine polyphenol resveratrol confers CV benefits, in part by exerting anti-inflammatory effects. However, the evidence in human long-term clinical trials has yet to be established. We aimed to investigate the effects of a dietary resveratrol-rich grape supplement on the inflammatory and fibrinolytic status of subjects at high risk of CVD and treated according to current guidelines for primary prevention of CVD. Seventy-five patients undergoing primary prevention of CVD participated in this triple-blinded, randomized, parallel, dose–response, placebo-controlled, 1-year follow-up trial. Patients, allocated in 3 groups, consumed placebo (maltodextrin), a resveratrol-rich grape supplement (resveratrol 8 mg), or a conventional grape supplement lacking resveratrol, for the first 6 months and a double dose for the next 6 months. In contrast to placebo and conventional grape supplement, the resveratrol-rich grape supplement significantly decreased high-sensitivity C-reactive protein (−26%, p = 0.03), tumor necrosis factor-α (−19.8%, p = 0.01), plasminogen activator inhibitor type 1 (−16.8%, p = 0.03), and interleukin-6/interleukin-10 ratio (−24%, p = 0.04) and increased anti-inflammatory interleukin-10 (19.8%, p = 0.00). Adiponectin (6.5%, p = 0.07) and soluble intercellular adhesion molecule-1 (−5.7%, p = 0.06) tended to increase and decrease, respectively. No adverse effects were observed in any patient. In conclusion, 1-year consumption of a resveratrol-rich grape supplement improved the inflammatory and fibrinolytic status in patients who were on statins for primary prevention of CVD and at high CVD risk (i.e., with diabetes or hypercholesterolemia plus ≥1 other CV risk factor). Our results show for the first time that a dietary intervention with grape resveratrol could complement the gold standard therapy in the primary prevention of CVD. [Copyright &y& Elsevier]

Abstract: Bacteria use Quorum Sensing (QS) systems to monitor their population density and to control a variety of physiological processes. In this study, the capacity of eleven phenolic compounds to inhibit QS signals in a biosensor strain (Chromobacterium violaceum) and two pathogenic bacteria (Yersinia enterocolitica and Erwinia carotovora) was evaluated. All the tested compounds inhibited QS regulated phenotypes in the biosensor strain. The identification and quantification of N-acyl-homoserine lactones (AHLs) by LC–MS/MS spectrometry showed that cinnamaldehyde, ellagic acid, pomegranate extract, resveratrol and rutin, at concentrations below their minimum inhibitory concentration, were able to reduce concentration of AHLs of both Y. enterocolitica and E. carotovora. [Copyright &y& Elsevier]

Physical exercise can produce changes in the microbiota, conferring health benefits through mechanisms that are not fully understood. We sought to determine the changes driven by exercise on the gut microbiota and on the serum and fecal metabolome using 16S rRNA gene analysis and untargeted metabolomics. A total of 85 serum and 12 fecal metabolites and six bacterial taxa (Romboutsia, Escherichia coli TOP498, Ruminococcaceae UCG-005, Blautia, Ruminiclostridium 9 and Clostridium phoceensis) were modified following a controlled acute exercise session. Among the bacterial taxa, Ruminiclostridium 9 was the most influenced by fecal and serum metabolites, as revealed by linear multivariate regression analysis. Exercise significantly increased the fecal ammonia content. Functional analysis revealed that alanine, aspartate and glutamate metabolism and the arginine and aminoacyl-tRNA biosynthesis pathways were the most relevant modified pathways in serum, whereas the phenylalanine, tyrosine and tryptophan biosynthesis pathway was the most relevant pathway modified in feces. Correlation analysis between fecal and serum metabolites suggested an exchange of metabolites between both compartments. Thus, the performance of a single exercise bout in cross-country non-professional athletes produces significant changes in the microbiota and in the serum and fecal metabolome, which may have health implications. [ABSTRACT FROM AUTHOR]

Sequencing the 16S gene rRNA has become a popular method when identifying bacterial communities. However, recent studies address differences in the characterization based on sample preparation, sequencing platforms, and data analysis. In this work, we tested some of the available user-friendly protocols for data analysis with the reads obtained from the sequencing machines Illumina MiSeq and Ion Torrent Personal Genome Machine (PGM). We sought for the advantages and disadvantages of both platforms in terms of accuracy, detected species, and abundance, analyzing a staggered mock community. Four different pipelines were applied: QIIME 1.9.1 with default parameters, QIIME 1.9.1 with modified parameters and chimera removal, VSEARCH 2.3.4, and QIIME 2 v.2018.2. To address the limitations of species level detection we used species-classifier SPINGO. The optimal pipeline for PGM platform, was the use of QIIME 1.9.1 with default parameters (QIIME1), except when a study requires the detection of Bacteroides or other Bacteroidaceae members, in which QIIME1MOD (with chimera removal) seems to be a good alternative. For Illumina Miseq, VSEARCH strategy can be a good option. Our results also confirm that all the tested pipelines can be used for metagenomic analysis at family and genus level. • 16S rRNA short-read sequence data gene presents limitations at species level. • For metagenomic analysis up to genus level, most classifiers perform well. • SPINGO classifier is useful to address the limitations at species level. • For PGM data, the optimal pipeline was QIIME 1.9.1 with default parameters. • All the protocols implemented in QIIME performed well for Illumina data. [ABSTRACT FROM AUTHOR]

Physical exercise is a tool to prevent and treat some of the chronic diseases affecting the world’s population. A mechanism through which exercise could exert beneficial effects in the body is by provoking alterations to the gut microbiota, an environmental factor that in recent years has been associated with numerous chronic diseases. Here we show that physical exercise performed by women to at least the degree recommended by the World Health Organization can modify the composition of gut microbiota. Using high-throughput sequencing of the 16s rRNA gene, eleven genera were found to be significantly different between active and sedentary women. Quantitative PCR analysis revealed higher abundance of health-promoting bacterial species in active women, including Faecalibacterium prausnitzii, Roseburia hominis and Akkermansia muciniphila. Moreover, body fat percentage, muscular mass and physical activity significantly correlated with several bacterial populations. In summary, we provide the first demonstration of interdependence between some bacterial genera and sedentary behavior parameters, and show that not only does the dose and type of exercise influence the composition of gut microbiota, but also the breaking of sedentary behavior. [ABSTRACT FROM AUTHOR]

Recent studies have revealed the importance of the gut microbiota in the regulation of metabolic phenotypes of highly prevalent metabolic diseases such as obesity, type II diabetes mellitus (T2DM) and cardiovascular disease. Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-activated nuclear receptors that interact with PPAR-γ co-activator-1α (PPARGC1A) to regulate lipid and glucose metabolism. Genetic polymorphisms in PPARD (rs 2267668; A/G) and PPARGC1A (rs 8192678; G/A) are linked to T2DM. We studied the association between the single-nucleotide polymorphisms (SNPs) rs 2267668 and rs 8192678 and microbiota signatures and their relation to predicted metagenome functions, with the aim of determining possible microbial markers in a healthy population. Body composition, physical exercise and diet were characterized as potential confounders. Microbiota analysis of subjects with PPARGC1A (rs 8192678) and PPARD (rs 2267668) SNPs revealed certain taxa associated with the development of insulin resistance and T2DM. Kyoto encyclopedia of gene and genomes analysis of metabolic pathways predicted from metagenomes highlighted an overrepresentation of ABC sugar transporters for the PPARGC1A (rs 8192678) SNP. Our findings suggest an association between sugar metabolism and the PPARGC1A rs 8192678 (G/A) genotype and support the notion of specific microbiota signatures as factors related to the onset of T2DM. [ABSTRACT FROM AUTHOR]

Purpose: Urolithins, gut microbiota metabolites derived from ellagic acid and ellagitannins, reach micromolar concentrations in the colon lumen where can have anti-inflammatory and anticancer effects. The antiproliferative activity of urolithins (Uro-A, Uro-B, Uro-C and Uro-D) and their most relevant in vivo glucuronides were evaluated in three human colon cancer cell lines (Caco-2, SW480 and HT-29). Methods: Cell proliferation was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and Trypan blue exclusion assays. Cell cycle was evaluated by flow cytometry and urolithins metabolism by HPLC-MS/MS. Results: Urolithins inhibited cell proliferation and cell cycle progression in a time- and dose-dependent manner and arrested the cells at S and G2/M phases, depending on the urolithin. Uro-A exerted the highest antiproliferative activity, followed by Uro-C, Uro-D and Uro-B. Unlike Caco-2 and SW480 cells, HT-29 cells partially overcame the effects after 48 h, which was related to the complete glucuronidation of urolithins. Uro-A or Uro-B glucuronides did not affect cell cycle and showed lower antiproliferative activity than their aglycone counterparts. Uro-A or Uro-B plus inhibitors of drug efflux ABC transporters partially prevented the glucuronidation of urolithins in HT-29 cells which became more sensitive. Conclusions: Uro-A, Uro-B, Uro-C and Uro-D exerted different antiproliferative effects depending on the colon cancer cell line. We also report here, for the first time, the role of ABC transporters and Phase-II metabolism in HT-29 cells as a mechanism of cancer resistance against urolithins due to their conversion to glucuronide conjugates that exerted lower antiproliferative activity. [ABSTRACT FROM AUTHOR]

Abstract: Metabolic and cardiovascular diseases (CVDs) have risen to alarming proportions, and there is a need for therapeutic and preventive measures. The polyphenol resveratrol (RES) protects against CVDs, but in vivo molecular mechanisms responsible for protection are not yet understood. Peripheral blood mononuclear cells (PBMNCs) are involved in the development of atherosclerosis and metabolic disorders. The identification of PBMNCs genes responding to dietary compounds might help to understand the mechanisms underlying the effects of polyphenols. We determined gene expression differences between PBMNCs from pigs fed a high-fat diet manifesting a mild increase of cholesterol and pigs fed a high-fat diet containing low doses of RES. Although the consumption of RES did not modify the levels of cholesterol, microarray analyses indicated that some of the differentially expressed genes, collagens (COL1A, COL3A), lipoprotein lipase (LPL) and fatty-acid binding proteins (FABPs) involved in CVDs and lipid metabolism were up-regulated by the high-fat diet and down-regulated by RES. Reverse transcriptase polymerase chain reaction confirmed that RES and RES-containing grape extract prevented the induction of FABP4 in PBMNCs in female pigs fed a high-fat diet. Low micromolar concentrations of RES and its metabolite dihydroresveratrol exerted a minor but significant reducing effect on the induction of FABP4 expression in human macrophages treated with oxidized low-density lipoprotein. Our results show that the consumption of low doses of RES modulates the expression of genes related to lipid metabolism and metabolic disorders that are affected by a high-fat diet and suggest that some of the circulating RES metabolites may contribute to these effects. [Copyright &y& Elsevier]

Background: Rosemary (Rosmarinus officinalis L.) extracts (REs) exhibit hepatoprotective, anti-obesity and anti-inflammatory properties and are widely used in the food industry. REs are rich in carnosic acid (CA) and carnosol which may be responsible for some of the biological activities of REs. The aim of this study was to investigate whether inhibition of lipase activity in the gut may be a mechanism by which a RE enriched in CA (40%) modulates body weight and lipids levels in a rat model of metabolic disorders and obesity. Methods and Principal Findings: RE was administered for 64 days to lean (fa/+) and obese (fa/fa) female Zucker rats and body weight, food intake, feces weight and blood biochemical parameters were monitored throughout the study. Lipase activity (hydrolysis of p-nitrophenylbutyrate) was measured in the gastrointestinal tract at the end of the study and the contents of CA, carnosol and methyl carnosate were also determined. Sub-chronic administration of RE moderately reduced body weight gain in both lean and obese animals but did not affect food intake. Serum triglycerides, cholesterol and insulin levels were also markedly decreased in the lean animals supplemented with RE. Importantly, lipase activity was significantly inhibited in the stomach of the RE-supplemented animals where the highest content of intact CA and carnosol was detected. Conclusions: Our results confirm that long-term administration of RE enriched in CA moderates weight gain and improves the plasma lipids profile, primarily in the lean animals. Our data also suggest that these effects may be caused, at least in part, by a significant inhibition of gastric lipase and subsequent reduction in fat absorption. [ABSTRACT FROM AUTHOR]

Abstract: The aim of the present work was to verify whether extra-virgin olive oil, a food naturally containing phenolic antioxidants, has the potential to protect from the pro-aging effects of a high-calorie diet. Male rats were fed from age 12 months to senescence a high-calorie diet containing either corn oil (CO), or extra-virgin olive oil with high (H-EVOO) or low (L-EVOO) amounts of phenols. The prolonged high fat intake led to obesity, liver lipid degeneration and insulin resistance, which were not counteracted by high phenol intake. No difference in overall survival was found at the end of the experiment in the animals treated with H-EVOO compared to the other groups. However, we did detect a protective effect of olive oil on some age-related pathologies and on blood pressure, of which the former was associated with the antioxidant content. Concomitantly, a decrease in DNA oxidative damage in blood cells and plasma TBARS and an increase in liver superoxide dismutase were detected following H-EVOO consumption. Thus, although olive oil phenols cannot reverse the detrimental effects of a prolonged intake of high amounts of fat, improving the quality of olive oil in terms of antioxidant content can be beneficial. [Copyright &y& Elsevier]

Abstract: Plant polyphenols, such as flavonoids, comprise many compounds, ranging from simple phenolic molecules (i.e. flavonols, anthocyanins) to polymeric structures with high molecular weight (as proanthocyanidins, PAs). We investigated the effects of flavonoids by feeding Wistar rats Arabidopsis thaliana seeds carrying mutations in key enzymes of the flavonoid biosynthetic pathway (15% w/w seeds for 4 weeks). The seeds used were: Ws-2 wild-type containing flavonols and PAs, tt3-4 mutant containing flavonols only, ban-5 accumulating flavonols and anthocyanins, tt4-8 mutant, deprived of flavonoids. DNA oxidative damage was significantly reduced only in the liver of rats fed tt3-4 mutant seeds. Microarray analysis of the liver revealed down-regulation of genes associated with oxidative stress, Krebs cycle, electron transport and proteasome degradation in all experimental groups compared to the tt4-8-fed reference rats; therefore, these effects were due to the flavonol content and not to high molecular weight compounds. We observed a down-regulation of inflammatory response genes in the colon mucosa in ban-5- fed rats, probably due to anthocyanin content. In conclusion, flavonols exhibited antioxidant effects at systemic level, whereas high molecular weight flavonoids affected only the colon, probably due to their limited absorption. [Copyright &y& Elsevier]

• Chilean Ribes polyphenols were digested and tested in an in vitro model of gut microbiota. • Digested Chilean currants reduced branched chain fatty acids and SCFA throughout fermentation. • Both digested Ribes promoted the growth of Clostridium cluster XIVa. • Ribes punctatum increased Faecalibacterium prausnitzii population. Chilean currants (Ribes magellanicum and Ribes punctatum) are wild polyphenol-rich berries with interesting bioactivities in several in vitro models. The aim of this study was to investigate the effects of the pre-digested PEE (polyphenol-enriched extract) in a simulated colon model. Fruits were extracted, submitted to simulated gastrointestinal digestion and further colonic fermentation with feces from healthy human donors. Samples were taken at 1, 4, 8 and 24 h of incubation, monitoring pH, ammonia, branched-chain fatty acids (BCFA), short-chain fatty acids (SCFA) and bacterial growth. FOS (fructooligosaccharides) and fecal slurry without treatments were positive and negative control, respectively. Both Ribes species reduced (p < 0.05) both BCFA and SCFA at 24 h. R. punctatum promoted the growth (p < 0.05) of beneficial bacteria such as Clostridium cluster XIVa, and Faecalibacterium prausnitzii ; while a trend to increase Akkermansia muciniphila was observed. R. magellanicum increased (p < 0.05) Clostridium cluster XIVa population. Escherichia coli , Lactobacillus spp. and Bifidobacterium spp. remained unaffected. Our results suggest that polyphenols from R. punctatum and R. magellanicum may modulate both bacterial metabolism and some selected gut beneficial bacteria under simulated conditions. Therefore, Chilean currants might be useful as supplements to maintain a healthy colon; however, further in vivo studies are needed to confirm their effect and their mechanisms. [ABSTRACT FROM AUTHOR]

Short‐chain fatty acids are the major end products of bacterial metabolism in the large bowel. They derive mostly from the bacterial breakdown of carbohydrates and are known to have positive health benefits. Due to the biological relevance of these compounds it is important to develop efficient, cheap, fast, and sensitive analytical methods that enable the identification and quantification of the short‐chain fatty acids in a large number of biological samples. In this study, a gas chromatography‐mass spectrometry method was developed and validated for the analysis of short‐chain fatty acids in faecal samples. These volatile compounds were extracted with ethyl acetate and 4‐methyl valeric acid was used as an internal standard. No further cleanup, concentration, and derivatization steps were needed and the extract was directly injected onto the column. Recoveries ranged between 65 and 105%, and no matrix effects were observed. The proposed method has wide linear ranges, good inter‐ and intraday variability values (below 2.6 and 5.6%, respectively) and limits of detection between 0.49 μM (0.29 μg/g) and 4.31 μM (3.8 μg/g). The applicability of this analytical method was successfully tested in faecal samples from rats and humans. [ABSTRACT FROM AUTHOR]