Dysbiosis and Associated Stool Features Improve Prediction of Response to Biological Therapy in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Dysbiosis of the gut microbiota is considered a key contributor to inflammatory bowel disease (IBD) etiology. Here, we investigated potential associations between microbiota composition and the outcomes to biological therapies. METHODS: The study prospectively recruited 296 patients with active IBD (203 with Crohn's disease, 93 with ulcerative colitis) initiating biological therapy. Quantitative microbiome profiles of pretreatment and posttreatment fecal samples were obtained combining flow cytometry with 16S amplicon sequencing. Therapeutic response was assessed by endoscopy, patient-reported outcomes, and changes in fecal calprotectin. The effect of therapy on microbiome variation was evaluated using constrained ordination methods. Prediction of therapy outcome was performed using logistic regression with 5-fold cross-validation. RESULTS: At baseline, 65.9% of patients carried the dysbiotic Bacteroides2 (Bact2) enterotype, with a significantly higher prevalence among patients with ileal involvement (76.8%). Microbiome variation was associated with the choice of biological therapy rather than with therapeutic outcome. Only anti-tumor necrosis factor-α treatment resulted in a microbiome shift away from Bact2, concomitant with an increase in microbial load and butyrogen abundances and a decrease in potentially opportunistic Veillonella. Remission rates for patients hosting Bact2 at baseline were significantly higher with anti-tumor necrosis factor-α than with vedolizumab (65.1% vs 35.2%). A prediction model, based on anthropometrics and clinical data, stool features (microbial load, moisture, and calprotectin), and Bact2 detection predicted treatment outcome with 73.9% accuracy for specific biological therapies. CONCLUSION: Fecal characterization based on microbial load, moisture content, calprotectin concentration, and enterotyping may aid in the therapeutic choice of biological therapy in IBD.

Vitamin A deficiency and associated risk factors in children aged 12-59 months living in poorest municipalities in the South Region of Brazil.

OBJECTIVE: To estimate the prevalence of vitamin A deficiency (VAD) in children and associated risk factors. DESIGN: Analysis of data from a cross-sectional multicentre study performed in the primary care units of the municipalities from January to June 2015. The children's legal guardians answered a socio-economic questionnaire, and the children's blood samples were obtained by venipuncture. Plasma retinol was determined by HPLC. Plasma retinol values of <0·70 µmol/l were considered VDA. Poisson multiple regression with robust variance was used. Values of P < 0·05 were considered significant. The data were analysed in the SPSS software, 21.0. SETTING: Forty-eight poorest municipalities in the South Region of Brazil. PARTICIPANTS: Children (n 1503) aged 12-59 months. RESULTS: The prevalence of VAD in the sample was 1·9 % (95 % CI (0·5, 6·8)). The following risk factors were associated with the outcome in the final explanatory model: family received Bolsa Familia program benefits (PR = 3·19; 95 % CI (1·69, 6·02)), child was not being breastfed (PR = 5·22; 95 % CI (1·68, 16·18)) and stunting (PR = 4·75; 95 % CI (2·10, 10·73)). CONCLUSIONS: VAD did not represent a public health problem for children living in socio-economically vulnerable municipalities in the South Region of Brazil, suggesting a new panorama of this nutritional deficiency even in regions of low socio-economic conditions in these three states. Thus, in view of the current nutritional transition scenario, it is necessary to continuously monitor and improve public policies related to vitamin A supplementation in the country.

Impact of a Purified Blueberry Extract on In Vitro Probiotic Mucin-Adhesion and Its Effect on Probiotic/Intestinal Pathogen Systems.

Several arguments have been made to substantiate the need for natural antimicrobials for the food industry. With blueberry extracts, the most compelling are both their healthy connotation and the possibility of obtaining a multipurpose solution that can be an antioxidant, colorant, and antimicrobial. From an antimicrobial perspective, as blueberry/anthocyanin-rich extracts have been associated with a capacity to inhibit harmful bacteria while causing little to no inhibition on potential probiotic microorganisms, the study of potential benefits that come from synergies between the extract and probiotics may be of particular interest. Therefore, the present work aimed to evaluate the effect of an anthocyanin-rich extract on the adhesion of five different probiotics as well as their effect on the probiotics' capacity to compete with or block pathogen adhesion to a mucin/BSA-treated surface. The results showed that, despite some loss of probiotic adhesion, the combined presence of extract and probiotic is more effective in reducing the overall amount of adhered viable pathogen cells than the PROBIOTIC alone, regardless of the probiotic/pathogen system considered. Furthermore, in some instances, the combination of the extract with Bifidobacterium animalis Bo allowed for almost complete inhibition of pathogen adhesion.

Pomegranate Oil's Potential as an Anti-Obesity Ingredient.

In recent years, pomegranate oil has obtained more attention due to its content of conjugated linolenic acids and possible application in the prevention of many diseases. The purpose of this work was to evaluate the potential ability of pomegranate oil to modulate obesity-related metabolism and immune response using in vitro models. In this regard, pomegranate oil was characterized in terms of fatty acids profile, tocopherols and phytosterols, and antioxidant capacity. After evaluation of the safety profile, pomegranate oil's capacity to modulate obesity-related metabolism was evaluated through adipolysis and adipokines secretion quantification in 3T3-L1 differentiated adipocytes and hepatic lipid accumulation assay in Hep G2 hepatocytes. The immunomodulatory activity was evaluated in Caco-2 cells by quantification of pro-inflammatory cytokines IL-6, IL-8, and TNF-α. This oil showed high antioxidant capacity and was mainly composed of conjugated fatty acid, namely punicic acid. Its chemical composition was responsible for its capacity to reduce the lipid accumulation in Hep G2 cells and 3T3-L1 differentiated adipocytes. In short, pomegranate oil shows great potential for the development of functional foods and nutraceuticals targeting obesity.

Lippia grata essential oil complexed with ß-cyclodextrin ameliorates biochemical and behavioral deficits in an animal model of progressive parkinsonism.

Parkinson's disease (PD) is identified by the loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc), and is correlated to aggregates of proteins such as α-synuclein, Lewy's bodies. Although the PD etiology remains poorly understood, evidence suggests a main role of oxidative stress on this process. Lippia grata Schauer, known as "alecrim-do-mato", "alecrim-de-vaqueiro", "alecrim-da-chapada", is a native bush from tropical areas mainly distributed throughout the Central and South America. This plant species is commonly used in traditional medicine for relief of pain and inflammation conditions, and that has proven antioxidant effects. We evaluated the effects of essential oil of the L. grata after its complexed with ß-cyclodextrin (LIP) on PD animal model induced by reserpine (RES). Behavioral assessments were performed across the treatment. Upon completion the treatment, the animals were euthanized, afterwards their brains were isolated and processed for immunohistochemical and oxidative stress analysis. The LIP treatment delayed the onset of the behavior of catalepsy, decreased the number of oral movements and prevented the memory impairment on the novel object recognition task. In addition, the treatment with LIP protected against dopaminergic depletion in the SNpc and dorsal striatum (STRd), and decreased the α-syn immunoreactivity in the SNpc and hippocampus (HIP). Moreover, there was reduction of the oxidative stability index. These findings demonstrated that the LIP treatment has neuroprotective effect in a progressive parkinsonism model, suggesting that LIP could be an important source for novel treatment approaches in PD.

Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism.

OBJECTIVES: Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome's functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation. DESIGN: We performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice. RESULTS: Severe obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration. CONCLUSION: Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity. TRIAL REGISTRATION NUMBER: NCT02059538.

The bee venom active compound melittin protects against bicuculline-induced seizures and hippocampal astrocyte activation in rats.

Epilepsy is a chronic neuropathology characterized by an abnormal hyperactivity of neurons that generate recurrent, spontaneous, paradoxical and synchronized nerve impulses, leading or not to seizures. This neurological disorder affects around 70 million individuals worldwide. Pharmacoresistance is observed in about 30% of the patients and long-term use of antiepileptics may induce serious side effects. Thus, there is an interest in the study of the therapeutic potential of bioactive substances isolated from natural products in the treatment of epilepsy. Arthropod venoms contain neurotoxins that have high affinity for molecular structures in the neural tissue such as receptors, transporters and ion channels both in glial and neuronal membranes. This study evaluated the potential neuroprotective effect of melittin (MEL), an active compound of bee venom, in the bicuculline-induced seizure model (BIC) in rats. Male Wistar rats (3 months, 250-300 g) were submitted to surgery for the implantation of a unilateral cannula in the lateral ventricle. After the recovery period, rats received a microinjection of saline solution or MEL (0.1 mg per animal). Firstly, rats were evaluated in the open field (20 min) and in the elevated plus maze (5 min) tests after received microinjection of saline or MEL. After, 30 min later animals received BIC (100 mg/ml) or saline, and their behaviors were analyzed for 20 min in the open field according to a seizure scale. At the end, rats were euthanized, brains collected and processed to glial fibrillary acidic protein (GFAP) immunohistochemistry evaluation. No changes were observed in MEL-treated rats in the open field and elevated plus maze. However, 90% of MEL-treated animals were protected against seizures induced by BIC. There was an increase in the latency for the onset of seizures, accompanied by a reduction of GFAP-immunoreactivity cells in the dentate gyrus and CA1. Thus, our study suggests that MEL has an anticonvulsant potential, and further studies are needed to elucidate the mechanisms involved in this action.

Blueberry Counteracts Prediabetes in a Hypercaloric Diet-Induced Rat Model and Rescues Hepatic Mitochondrial Bioenergetics.

The paramount importance of a healthy diet in the prevention of type 2 diabetes is now well recognized. Blueberries (BBs) have been described as attractive functional fruits for this purpose. This study aimed to elucidate the cellular and molecular mechanisms pertaining to the protective impact of blueberry juice (BJ) on prediabetes. Using a hypercaloric diet-induced prediabetic rat model, we evaluated the effects of BJ on glucose, insulin, and lipid profiles; gut microbiota composition; intestinal barrier integrity; and metabolic endotoxemia, as well as on hepatic metabolic surrogates, including several related to mitochondria bioenergetics. BJ supplementation for 14 weeks counteracted diet-evoked metabolic deregulation, improving glucose tolerance, insulin sensitivity, and hypertriglyceridemia, along with systemic and hepatic antioxidant properties, without a significant impact on the gut microbiota composition and related mechanisms. In addition, BJ treatment effectively alleviated hepatic steatosis and mitochondrial dysfunction observed in the prediabetic animals, as suggested by the amelioration of bioenergetics parameters and key targets of inflammation, insulin signaling, ketogenesis, and fatty acids oxidation. In conclusion, the beneficial metabolic impact of BJ in prediabetes may be mainly explained by the rescue of hepatic mitochondrial bioenergetics. These findings pave the way to support the use of BJ in prediabetes to prevent diabetes and its complications.

Are olive pomace powders a safe source of bioactives and nutrients?

BACKGROUND: The olive oil industry generates significant amounts of semi-solid wastes, namely olive pomace. Olive pomace is a by-product rich in high-value compounds (e.g. dietary fibre, unsaturated fatty acids, polyphenols) widely explored to obtain new food ingredients. However, conventional extraction methods frequently use organic solvents, while novel eco-friendly techniques have high operational costs. The development of powdered products without any extraction step has been proposed as a more feasible and sustainable approach. RESULTS: The present study fractionated and valorized the liquid and pulp fraction of olive pomace obtaining two stable and safe powdered ingredients, namely a liquid-enriched powder (LOPP) and a pulp-enriched powder (POPP). These powders were characterized chemically, and their bioactivity was assessed. LOPP exhibited a significant amount of mannitol (141 g kg-1 ), potassium (54 g kg-1 ) and hydroxytyrosol derivatives (5 mg g-1 ). POPP exhibited a high amount of dietary fibre (620 g kg-1 ) associated with a significant amount of bound phenolics (7.41 mg GAE g-1 fibre DW) with substantial antioxidant activity. POPP also contained an unsaturated fatty acid composition similar to that of olive oil (76% of total fatty acids) and showed potential as a reasonable source of protein (12%). Their functional properties (solubility, water-holding and oil-holding capacity), antioxidant capacity and antimicrobial activity were also assessed, and their biological safety was verified. CONCLUSIONS: The development of olive pomace powders for application in the food industry could be a suitable strategy to add value to olive pomace and obtain safe multifunctional ingredients with higher health-promoting effects than dietary fibre and polyphenols. © 2020 Society of Chemical Industry.

Bioactive extracts from brewer's spent grain.

In this study, antioxidant-rich extracts from brewer's spent grain (BSG) extracted by solid-to-liquid extraction using different solvents water and ethanol and their mixtures at two ratios (80% ethanol : water (v/v) and 60% ethanol : water (v/v)) were characterized. Nutritional composition was evaluated for the extracts and for the solid residues obtained after extraction. Additionally, the extracts were analyzed for the total phenolic content and individual phenolic compounds and related biological properties including antioxidant capacity (ABTS; ORAC and DNA protection), antihypertensive capacity, antibacterial activity and antibiofilm capacity. Safety was also demonstrated through genotoxicity and cytotoxicity tests. The results obtained showed that while all the extracts exhibited high antioxidant capacity (except ethanolic extract), the highest values were obtained for the 60% ethanol : water extract. The identification of phenolic compounds using HPLC showed that catechin and vanillin were the main compounds identified with the highest concentration being obtained for 60% ethanol : water extraction. In the biological activity assays, water and hydroethanolic extracts were multifunctional (antioxidant and antihypertensive capacity, antibacterial and antibiofilm activity), and the 80% ethanol : water presented better results in some assays. All were non-genotoxic, but the cytotoxicity was dependent on the extract concentration, with complete safe application for all up to 1 mg mL-1. Therefore, this study shows the potential of a viable green solvent based and low cost extraction recovery method of bioactive compounds from brewer's spent grain.

Study of viability of high pressure extract from pomegranate peel to improve carrot juice characteristics.

Extracts from fruit processing by-products usually present high amounts of bioactive compounds with several important activities such as antioxidant and antimicrobial capacities. In this work we studied (i) the cytotoxicity profile of pomegranate peel extract and (ii) safety and quality aspects after incorporating this extract in carrot juice - a beverage with low antioxidant potential and highly prone to microbial growth. The extract was obtained by high-pressure extraction and was non-cytotoxic towards the Caco-2 cell line after in vitro digestion. The non-cytotoxic pomegranate peel extract was added to carrot juice in a concentration of 5 mg mL-1. Fortified juices were processed by high-pressure and conventional heat and stored under refrigeration. On the 28th day of storage, microbial counts in PPE-fortified juices were reduced by 1.0 log10 CFU mL-1 and the pressurized juices showed significantly fewer counts than the thermal-treated ones. Just after processing, phenolic and flavonoid contents, as well as ABTS and FRAP antioxidant capacities, increased 3.6, 3.5, 8.2, and 9.4-fold, respectively in the fortified juices. The extract addition did not affect any colour parameter and all studied physicochemical parameters i.e. total soluble solids, pH, colour, total phenolics, flavonoids, hydrolysable tannins, and antioxidant capacity remained constant throughout storage. These findings could pave the way towards the development of safe beverages with improved bioactive properties.

A new MAP-Rasagiline conjugate reduces α-synuclein inclusion formation in a cell model.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease of the elderly. Current therapies are only symptomatic, and have no disease-modifying effect. Therefore, disease progresses continuously over time, presenting with both motor and non-motor features. The precise molecular basis for PD is still elusive, but the aggregation of the protein alpha-synuclein (α-syn) is a key pathological hallmark of the disease and is, therefore, a major focus of current research. Considering the intrinsic properties of cell-penetrating peptides (CPPs) for mediating drug delivery of neurotherapeutics across the blood brain barrier (BBB), these might open novel opportunities for the development of new solutions for the treatment of brain-related aspects of PD and other neurodegenerative disorders. METHODS: Here, we synthesized solid-phase CPPs using an amphipathic model peptide (MAP) conjugated with the drug Rasagiline (RAS), which we named RAS-MAP, and evaluated its effect on α-syn inclusion formation in a human cell-based model of synucleinopathy. RESULTS: We found that treatment with RAS-MAP at low concentrations (1-3 µM) reduced α-syn aggregation in cells. CONCLUSIONS: For the first time, we report that conjugation of a current drug used in the therapy of PD with CPP reduces α-syn aggregation, which might prove beneficial in PD and other synucleinopathies.

Effect of high hydrostatic pressure extraction on biological activities of stinging nettle extracts.

Stinging nettle is traditionally used as a therapeutic herb. In the present work, the biological properties and toxicity of novel nettle leaf extracts obtained by high pressure assisted extraction (HPE) were studied and compared with similar extracts obtained with the same solvent under atmospheric pressure conditions. The studied extracts were obtained at pressure levels of 200 and 500 MPa, ≈10 min, 0 to 70% ethanol : water (v/v). Each extract was characterized for its individual compound profile and different biological properties, such as antioxidant activity, pro-oxidant activity (DNA degradation capacity) and antihypertensive activity, as well as cytotoxicity against Caco-2 and HaCat cell cultures. The main results indicate that in addition to the antioxidant and antihypertensive activities observed for the control extracts, a clear improvement of all the biological activities of the extracts obtained by HPE was observed. The extracts obtained at 200 MPa, 10 min, 35 and 70% ethanol were the ones presenting higher concentrations of phenolic acids and flavonoids, such as chlorogenic acid, isoferulic acid, and rutin; besides, they showed better results concerning all the studied biological activities. Those extracts also showed potential for DNA protection, since they were able not only to cause less damage in the DNA molecule than the controls, but also showed no pro-oxidant activity. Concerning cytotoxicity, it was observed that HPE extracts, at a concentration up to 1.0 mg mL-1, presented a metabolism inhibition below 10 and 15% for Caco-2 and HaCat cell lines, respectively.

Impact of plant extracts upon human health: A review.

With the increase in evidences directly linking diet and health, several foodstuffs, such as phenolic rich fruits and vegetables, have emerged as possessing potential health benefits. Plants, given their fiber and phenolic content (and their intrinsic biological potential), have long been considered as contributing to health promotion. Therefore, the present work aimed to review the existing evidences regarding the various potential benefits of plant extracts' and plant extract-based products' consumption, with emphasis on in vivo works and epidemiological studies whenever available. Overall, the information available supports that, while there are indications of the potential benefits of plant extracts' consumption, further human-based studies are still needed to establish a true cause-effect.

The Health-Promoting Potential of Salix spp. Bark Polar Extracts: Key Insights on Phenolic Composition and In Vitro Bioactivity and Biocompatibility.

Salix spp. have been exploited for energy generation, along with folk medicine use of bark extracts for antipyretic and analgesic benefits. Bark phenolic components, rather than salicin, have demonstrated interesting bioactivities, which may ensure the sustainable bioprospection of Salix bark. Therefore, this study highlights the detailed phenolic characterization, as well as the in vitro antioxidant, anti-hypertensive, Staphylococcus aureus growth inhibitory effects, and biocompatibility of Salix atrocinerea Brot., Salix fragilis L., and Salix viminalis L. bark polar extracts. Fifteen phenolic compounds were characterized by ultra-high-performance liquid chromatography-ultraviolet detection-mass spectrometry analysis, from which two flavan-3-ols, an acetophenone, five flavanones, and a flavonol were detected, for the first time, as their bark components. Salix bark extracts demonstrated strong free radical scavenging activity (5.58-23.62 µg mL-1 IC50 range), effective inhibition on angiotensin-I converting enzyme (58-84%), and S. aureus bactericidal action at 1250-2500 µg mL-1 (6-8 log CFU mL-1 reduction range). All tested Salix bark extracts did not show cytotoxic potential against Caco-2 cells, as well as S. atrocinerea Brot. and S. fragilis L. extracts at 625 and 1250 µg mL-1 against HaCaT and L929 cells. These valuable findings can pave innovative and safer food, nutraceutical, and/or cosmetic applications of Salix bark phenolic-containing fractions.

Dimethylaminoparthenolide reduces the incidence of dysplasia and ameliorates a wasting syndrome in HPV16-transgenic mice.

The nuclear factor kappa light chain enhancer of activated B cells (NF-κB) has been implicated in the progression of cancers induced by high-risk human papillomaviruses (HPV). In cancer patients, NF-κB is also thought to drive a chronic systemic inflammatory status, leading to cachexia. This study addressed the ability of dimethylaminoparthenolide (DMAPT), a water-soluble NF-κB inhibitor, to block the development of HPV-induced lesions and wasting syndrome in HPV16-transgenic mice. Mice received DMAPT orally (100 mg/kg/day), once a day, for 6 consecutive weeks. Body weight was monitored weekly along with food and water intake. After 6 weeks the animals were submitted to a grip strength test and sacrificed for specimen collection. Skin samples were analyzed histologically and for expression of NF-κB-regulated genes Bcl2 and Bcl2l1. Gastrocnemius muscles were weighted and analyzed for expression of NF-κB subunits p50, p52, p65, and Rel-B. DMAPT reduced the incidence of epidermal dysplasia (18.2% versus 33.3% in HPV16+/- untreated mice). This was associated with reduced expression of Bcl2 and Bcl2l1 (p = .0003 and p = .0014, respectively) and reduced neutrophilic infiltration (p = .0339). Treated mice also showed partially preserved bodyweight and strength, which were independent of the expression levels of NF-κB subunits in skeletal muscle.These results suggest that NF-κB inhibition may be a valid strategy against HPV-induced lesions in vivo and warrant further preclinical tests particularly in the set of combination therapies. In addition, the data may support the use of DMAPT to prevent wasting syndrome.

Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study.

Metabolic syndrome is characterized by a constellation of comorbidities that predispose individuals to an increased risk of developing cardiovascular pathologies as well as type 2 diabetes mellitus1. The gut microbiota is a new key contributor involved in the onset of obesity-related disorders2. In humans, studies have provided evidence for a negative correlation between Akkermansia muciniphila abundance and overweight, obesity, untreated type 2 diabetes mellitus or hypertension3-8. Since the administration of A. muciniphila has never been investigated in humans, we conducted a randomized, double-blind, placebo-controlled pilot study in overweight/obese insulin-resistant volunteers; 40 were enrolled and 32 completed the trial. The primary end points were safety, tolerability and metabolic parameters (that is, insulin resistance, circulating lipids, visceral adiposity and body mass). Secondary outcomes were gut barrier function (that is, plasma lipopolysaccharides) and gut microbiota composition. In this single-center study, we demonstrated that daily oral supplementation of 1010 A. muciniphila bacteria either live or pasteurized for three months was safe and well tolerated. Compared to placebo, pasteurized A. muciniphila improved insulin sensitivity (+28.62 ± 7.02%, P = 0.002), and reduced insulinemia (-34.08 ± 7.12%, P = 0.006) and plasma total cholesterol (-8.68 ± 2.38%, P = 0.02). Pasteurized A. muciniphila supplementation slightly decreased body weight (-2.27 ± 0.92 kg, P = 0.091) compared to the placebo group, and fat mass (-1.37 ± 0.82 kg, P = 0.092) and hip circumference (-2.63 ± 1.14 cm, P = 0.091) compared to baseline. After three months of supplementation, A. muciniphila reduced the levels of the relevant blood markers for liver dysfunction and inflammation while the overall gut microbiome structure was unaffected. In conclusion, this proof-of-concept study (clinical trial no. NCT02637115 ) shows that the intervention was safe and well tolerated and that supplementation with A. muciniphila improves several metabolic parameters.

l-arginine minimizes immunosuppression and prothrombin time and enhances the genotoxicity of 5-fluorouracil in rats.

OBJECTIVE: The aim of this study was to evaluate the effect of low doses of l-arginine supplementation on hemogram, integrity of DNA and spleen, inflammatory infiltrate in the jejunum, and in the coagulogram of rats submitted to 5-fluorouracil (5-FU) chemotherapy. METHODS: Thirty-two Wistar rats were fed commercial feed and water ad libitum and grouped into four (eight rats per group): The control group was given a 0.9% physiologic solution to simulate the application of 5-FU in the other groups; the G5-FU group was given a dose of 5-FU; the GArg50 and GArg100 groups were given a dose of 5-FU and supplemented with 50 and 100 mg l-arginine/d added in the drinking water ad libitum. RESULTS: The rats in the GArg50 group did not lose weight after chemotherapy. GArg50 rats presented polycythemia owing to dehydration caused by diarrhea generated by 5-FU. GArg100 rats had increased total leukocyte count, eosinophils, lymphocytes, and index in the total index of DNA damage, yet showed a reduction in prothrombin time and in the spleen depletion index. Rats in the G5-FU, GArg50, and GArg100 groups had similar moderate inflammatory infiltrate in the jejunum. CONCLUSION: Supplementation with 100 mg/d of l-arginine minimized immunosuppression, spleen depletion, and prothrombin time and contributed to the breakdown of 5-FU-generated DNA in Wistar rats. Supplementation with 50 mg/d of l-arginine decreased the weight loss generated by 5-FU in Wistar rats. Supplements with 50 or 100 mg of l-arginine did not interfere with 5-FU-generated jejunal inflammatory infiltrate.

Antimicrobial activity of pomegranate peel extracts performed by high pressure and enzymatic assisted extraction.

This study aimed to assess the effect of high pressure (300 and 600 MPa) and enzymatic extraction (pectinase and cellulase) on the phenolic compounds profile, antioxidant capacity and antimicrobial activity of extracts from pomegranate by-products. Antimicrobial activity against eight different strains of pathogenic and contaminant bacteria and against five beneficial bacteria including Lactobacillus and Bifidobacterium strains were determined. The maximum level of total phenolic content, as well as antioxidant capacity were observed at 300 MPa, however enzymatic extraction did not improve the extraction yields. Punicalagin isomers and bis-hexahydroxydiphenoyl-glucoside isomer were the most abundant phenolic compounds found in the extracts. All pomegranate peel extracts demonstrated selective antimicrobial activity against all pathogenic bacteria without affecting beneficial ones. Pressurized extracts presented lower minimum inhibitory concentration against Bacillus cereus and Pseudomonas aeruginosa and lower minimum bactericidal concentration against B. cereus, while, enzymatic extracts presented lower minimum bactericidal concentration for Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus and Listeria monocytogenes. Principal component analyses reveled that antioxidant activity and phenolic compounds content were strongly related with antimicrobial activity. Pomegranate peels extracts obtained by high pressure extraction could so be used as a source of high added-value bioactive compounds for antioxidant and antimicrobial applications.