Plant-based food interventions are promising therapeutic approaches for non-alcoholic fatty liver disease (NAFLD) treatment, and microRNAs (miRNAs) have emerged as functional bioactive components of dietary plants involved in cross-kingdom communication. Deeper investigations are needed to determine the potential impact of plant miRNAs in NAFLD. This study aimed to identify plant miRNAs that could eventually modulate the expression of human metabolic genes and protect against the progression of hepatic steatosis. Plant miRNAs from the miRBase were used to predict human target genes, and miR8126-3p and miR8126-5p were selected as candidates for their potential role in inhibiting glucose and lipid metabolism-related genes. Human HepG2 cells were transfected with plant miRNA mimics and then exposed to a mixture of oleic and palmitic acids to mimic steatosis. miR8126-3p and miR8126-5p transfections inhibited the expression of the putative target genes QKI and MAPKAPK2, respectively, and had an impact on the expression profile of key metabolic genes, including PPARA and SREBF1. Quantification of intrahepatic triglycerides revealed that miR8126-3p and miR8126-5p attenuated lipid accumulation. These findings suggest that plant miR8126-3p and miR8126-5p would induce metabolic changes in human hepatocytes eventually protecting against lipid accumulation, and thus, they could be potential therapeutic tools for preventing and alleviating lipid accumulation.

This study aims to provide a thorough characterization of Brij O2-stabilized gliadin nanoparticles to be used for the potential oral administration of various compounds. Different techniques were used in order to evaluate their physico-chemical features and then in vivo studies in rats were performed for the investigation of their biodistribution and gastrointestinal transit profiles. The results showed that the gliadin nanoparticles accumulated in the mucus layer of the bowel mucosa and evidenced their ability to move along the digestive systems of the animals. The incubation of the nanosystems with Caenorhabditis elegans, used as an additional in vivo model, confirmed the intake of the particles and evidenced their presence along the entire gastrointestinal tract of these nematodes. The gliadin nanoparticles influenced neither the egg-laying activity of the worms nor their metabolism of lipids up to 10 & mu;g/mL of nanoformulation. The systems decreased the content of the age-related lipofuscin pigment in the nematodes in a dose-dependent manner, demonstrating a certain antioxidant activity. Lastly, dihydroethidium staining showed the absence of oxidative stress upon incubation of the worms together with the formulations, confirming their safe profile. This data paves the way for the future application of the proposed nanosystems regarding the oral delivery of various bioactives.

Aims/hypothesis Modulation of gut microbiota has emerged as a promising strategy to treat or prevent the development of different metabolic diseases, including type 2 diabetes and obesity. Previous data from our group suggest that the strain Pediococcus acidilactici CECT9879 (pA1c) could be an effective probiotic for regulating glucose metabolism. Hence, the objectives of this study were to verify the effectiveness of pA1c on glycaemic regulation in diet-induced obese mice and to evaluate whether the combination of pA1c with other normoglycaemic ingredients, such as chromium picolinate (PC) and oat beta-glucans (BGC), could increase the efficacy of this probiotic on the regulation of glucose and lipid metabolism. Methods Caenorhabditis elegans was used as a screening model to describe the potential synbiotic activities, together with the underlying mechanisms of action. In addition, 4-week-old male C57BL/6J mice were fed with a high-fat/high-sucrose diet (HFS) for 6 weeks to induce hyperglycaemia and obesity. Mice were then divided into eight groups (n=12 mice/group) according to dietary supplementation: control-diet group; HFS group; pA1c group (10(10) colony-forming units/day); PC; BGC; pA1c+PC+BGC; pA1c+PC; and pA1c+BGC. Supplementations were maintained for 10 weeks. Fasting blood glucose was determined and an IPGTT was performed prior to euthanasia. Fat depots, liver and other organs were weighed, and serum biochemical variables were analysed. Gene expression analyses were conducted by real-time quantitative PCR. Sequencing of the V3-V4 region of the 16S rRNA gene from faecal samples of each group was performed, and differential abundance for family, genera and species was analysed by ALDEx2R package. Results Supplementation with the synbiotic (pA1c+PC+BGC) counteracted the effect of the high glucose by modulating the insulin-IGF-1 signalling pathway in C. elegans, through the reversal of the glucose nuclear localisation of daf-16. In diet-induced obese mice, all groups supplemented with the probiotic significantly ameliorated glucose tolerance after an IPGTT, demonstrating the glycaemia-regulating effect of pA1c. Further, mice supplemented with pA1c+PC+BGC exhibited lower fasting blood glucose, a reduced proportion of visceral adiposity and a higher proportion of muscle tissue, together with an improvement in the brown adipose tissue in comparison with the HFS group. Besides, the effect of the HFS diet on steatosis and liver damage was normalised by the synbiotic. Gene expression analyses demonstrated that the synbiotic activity was mediated not only by modulation of the insulin-IGF-1 signalling pathway, through the overexpression of GLUT-1 and GLUT-4 mediators, but also by a decreased expression of proinflammatory cytokines such as monocyte chemotactic protein-1. 16S metagenomics demonstrated that the synbiotic combinations allowed an increase in the concentration of P. acidilactici, together with improvements in the intestinal microbiota such as a reduction in Prevotella and an increase in Akkermansia muciniphila. Conclusions/interpretation Our data suggest that the combination of pA1c with PC and BGC could be a potential synbiotic for blood glucose regulation and may help to fight insulin resistance, diabetes and obesity.

Due to the importance of the gut microbiota in the regulation of energy homeostasis, probiotics have emerged as an alternative therapy to ameliorate obesity-related disturbances, including cholesterol metabolism dysregulation, dyslipidemia and inflammation. Therefore, the objectives of this study were to evaluate the effect of the probiotic strain Pediococcus acidilactici (pA1c (R)) on the regulation of adiposity, cholesterol and lipid metabolism, inflammatory markers and gut microbiota composition in diet-induced obese rats. Twenty-nine four-week-old male Wistar rats were divided into three groups: rats fed a control diet (CNT group, n = 8), rats fed a high fat/high sucrose diet (HFS group, n = 11), and rats fed a HFS diet supplemented with pA1c (R) (pA1c (R) group, n = 10). Organs and fat depots were weighed, and different biochemical parameters were analysed in serum. Gene expression analyses in the adipose tissue were conducted using real-time quantitative-PCR. Faecal microbiota composition was evaluated using 16S metagenomics. Animals supplemented with pA1c (R) exhibited a lower proportion of visceral adiposity, a higher proportion of muscle, an improvement in the total-cholesterol/HDL-cholesterol ratio and a decrease in the total cholesterol, triglyceride and aspartate aminotransaminase (AST) serum levels, together with a decrease in several inflammation-related molecules. The expression of key genes related to adipose (Adipoq, Cebpa and Pparg) and glucose (Slc2a1 and Slc2a4) metabolism in the adipose tissue was normalized by pA1c (R). Moreover, it was demonstrated that pA1c (R) supplementation activated fatty acid beta-oxidation in the adipose tissue and the liver. Metagenomics demonstrated the presence of pA1c (R) in the faecal samples, an increase in alpha diversity, an increase in the abundance of beneficial bacteria, and a decrease in the abundance of harmful micro-organisms, including the Streptococcus genus. Thus, our data suggest the potential of pA1c (R) in the prevention of obesity-related disturbances including hypercholesterolemia, hypertriglyceridemia, inflammation and gut microbiota dysbiosis.

Background: Edible plants can exert anti-inflammatory activities in humans, being potentially useful in the treatment of inflammatory diseases. Plant-derived microRNAs have emerged as cross-kingdom gene expression regulators and could act as bioactive molecules involved in the beneficial effects of some edible plants. We investigated the role of edible plant-derived microRNAs in the modulation of pro-inflammatory human genes.Methods: MicroRNAs from plant-derived foods were identified by next-generation sequencing. MicroRNAs with inflammatory putative targets were selected, after performing in silico analyses. The expression of candidate plant-derived miRNAs was analyzed by qPCR in edible plant-derived foods and their effects were evaluated in THP-1 monocytes differentiated to macrophages. The bioavailability of candidate plant miRNAs in humans was evaluated in feces and serum samples by qPCR.Results: miR482f and miR482c-5p are present in several edible plant-derived foods, such as fruits, vegetables, and cooked legumes and cereals, and fats and oils. Transfections with miR482f and miR482c-5p mimics decreased the gene expression of CLEC7A and NFAM1, and TRL6, respectively, in human THP-1 monocytes differentiated to macrophages, which had an impact on gene expression profile of inflammatory biomarkers. Both microRNAs (miR482f and miR482c-5p) resisted degradation during digestion and were detected in human feces, although not in serum.Conclusion: Our findings suggest that miR482f and miR482c-5p can promote an anti-inflammatory gene expression profile in human macrophages in vitro and their bioavailability in humans can be achieved through diet, but eventually restricted at the gut level.

The increasing prevalence of metabolic syndrome-related diseases, including type-2 diabetes and obesity, makes it urgent to develop new alternative therapies, such as probiotics. In this study, we have used Caenorhabditis elegans under a high-glucose condition as a model to examine the potential probiotic activities of Pediococcus acidilactici CECT9879 (pA1c). The supplementation with pA1c reduced C. elegans fat accumulation in a nematode growth medium (NGM) and in a high-glucose (10 mM) NGM medium. Moreover, treatment with pA1c counteracted the effect of the high glucose by reducing reactive oxygen species by 20%, retarding the aging process and extending the nematode median survival (> 2 days in comparison with untreated control worms). Gene expression analyses demonstrated that the probiotic metabolic syndrome-alleviating activities were mediated by modulation of the insulin/IGF-1 signaling pathway (IIS) through the reversion of the glucose-nuclear-localization of daf-16 and the overexpression of ins-6 and daf-16 mediators, increased expression of fatty acid (FA) peroxisomal beta-oxidation genes, and downregulation of FA biosynthesis key genes. Taken together, our data suggest that pA1c could be considered a potential probiotic strain for the prevention of the metabolic syndrome-related disturbances and highlight the use of C. elegans as an appropriate in vivo model for the study of the mechanisms underlying these diseases.

Background and aim Fecal microbiome disturbances are linked to different human diseases. In the case of obesity, gut microbiota seems to play a role in the development of low-grade inflammation. The purpose of the present study was to identify specific bacterial families and genera associated with an increased obesity-related inflammatory status, which would allow to build a regression model for the prediction of the inflammatory status of obese and overweight subjects based on fecal microorganisms. Methods A total of 361 volunteers from the Obekit trial (65 normal-weight, 110 overweight, and 186 obese) were classified according to four variables: waist/hip ratio (>= 0.86 for women and >= 1.00 for men), leptin/adiponectin ratio (LAR, >= 3.0 for women and >= 1.4 for men), and plasma C-reactive protein (>= 2 mg/L) and TNF levels (>= 0.85 pg/mL). An inflammation score was designed to classify individuals in low (those subjects who did exceed the threshold value in 0 or 1 variable) or high inflammatory index (those subjects who did exceed the threshold value in 2 or more variables). Fecal 16 S rRNA sequencing was performed for all participants, and differential abundance analyses for family and genera were performed using the MicrobiomeAnalyst web-based platform. Results Methanobacteriaceae, Christensenellaceae, Coriobacteriaceae, Bifidobacteriaceae, Catabacteriaceae, and Dehalobacteriaceae families, and Methanobrevibacter, Eggerthella, Gemmiger, Anaerostipes, and Collinsella gen

In this work, a bioactive persimmon extract was produced from discarded fruits. A central composite design was used to evaluate the effect of different extraction parameters and ripeness stages of persimmon fruits on the total phenolic content and antioxidant activity of the resulting extracts. Significantly greater phenolic contents were obtained from immature persimmon (IP) fruits. The optimum IP extract with the conditions set by the experimental design was industrially up-scaled and its composition and functional properties were evaluated and compared with those obtained under lab-scale conditions. Both extracts contained significant protein (>20%) and phenolic contents (similar to 11-27 mg GA/g dry extract) and displayed significant antiviral activity against murine norovirus and hepatitis A virus. Moreover, the extract showed no toxicity and significantly reduced the fat content and the cellular ageing of Caenorhabditis elegans (C. elegans) without affecting the worm development. These effects were mediated by down-regulation of fat-7, suggesting an anti-lipogenic activity of this extract.

Purpose Obesity has been related to intestinal dysbiosis and the modification of gut microbiota composition by dietary strategies becomes a promising strategy to help manage obesity. The aim of the current study was to evaluate the effect of two weight-loss diets on the composition and functional profile of gut microbiota. Methods 55 men and 124 women with BMI > 25 kg/m(2) were randomly assigned to moderately high-protein (MHP) or low-fat (LF) diet. Differences in fecal bacteria abundance (based on 16 s rRNA sequencing) between before and after 4 months of calorie restriction was analyzed using EdgeR tool in MicrobiomeAnalyst platform. Bacterial functional profile was predicted using Tax4Fun and metagenomeSeq analysis. Significant KEGG Orthology (KO) terms were selected for the metabolomic study using chromatography. Results After the intervention, MHP-men showed a significant decrease in Negativicutes, Selenomonadales, Dielma and Dielma fastidiosa. LF-men showed a significant increase in Bacilli, Lactobacillales, Christensenellaceae, Peptococcaceae, and Streptococcaceae, Peptococcus, Streptococcus and Christensenella, Duncaniella dubosii_CP039396_93.49%, Roseburia sp_AB744234_98.96% and Alistipes inops_KJ572413_99.57%. MHP-women increased Pasteurellales, Phascolarctobacterium succinatutens, Ruthenibacterium lactatiformans_LR215981_99.55% and decreased in Phascolarctobacterium succinatutens_NR112902_99.56%. Finally, LF-women presented a significant decrease in Bacteroides clarus and Erysipelothrix inopinata_CP060715_84.4%. Surprisingly, no matching bacterial changes were found between these four groups. A total of 42 KO, 10 metabolic pathways and 107 related metabolites related were found implicated in these bacterial changes. Seven metabolites were confirmed in plasma. Conclusion Weight-loss-related-changes in gut microbiome composition and the functional profile occur in a sex- and diet-related manner, showing that women and men could differentially benefit from the consumption of MHP and LF diets.

In recent years, food ingredients rich in bioactive compounds have emerged as candidates to prevent excess adiposity and other metabolic complications characteristic of obesity, such as low-grade inflammation and oxidative status. Among them, fungi have gained popularity for their high polysaccharide content and other bioactive components with beneficial activities. Here, we use the C. elegans model to investigate the potential activities of a Grifola frondosa extract (GE), together with the underlying mechanisms of action. Our study revealed that GE represents an important source of polysaccharides and phenolic compounds with in vitro antioxidant activity. Treatment with our GE extract, which was found to be nongenotoxic through a SOS/umu test, significantly reduced the fat content of C. elegans, decreased the production of intracellular ROS and aging-lipofuscin pigment, and increased the lifespan of nematodes. Gene expression and mutant analyses demonstrated that the in vivo anti-obesity and antioxidant activities of GE were mediated through the daf-2/daf-16 and skn-1/nrf-2 signalling pathways, respectively. Taken together, our results suggest that our GE extract could be considered a potential functional ingredient for the prevention of obesity-related disturbances.