Plasma Bacterial DNA Load as a Potential Biomarker for the Early Detection of Colorectal Cancer: A Case-Control Study.

The gut microbiota has gained increasing attention in recent years due to its significant impact on colorectal cancer (CRC) development and progression. The recent detection of bacterial DNA load in plasma holds promise as a potential non-invasive approach for early cancer detection. The aim of this study was to examine the quantity of bacterial DNA present in the plasma of 50 patients who have CRC in comparison to 40 neoplastic disease-free patients, as well as to determine if there is a correlation between the amount of plasma bacterial DNA and various clinical parameters. Plasma bacterial DNA levels were found to be elevated in the CRC group compared to the control group. As it emerged from the logistic analysis (adjusted for age and gender), these levels were strongly associated with the risk of CRC (OR = 1.02, p < 0.001, 95% C.I.: 1.01-1.03). Moreover, an association was identified between a reduction in tumor mass and the highest tertile of plasma bacterial DNA. Our findings indicate that individuals with CRC displayed a higher plasma bacterial DNA load compared to healthy controls. This observation lends support to the theory of heightened bacterial migration from the gastrointestinal tract to the bloodstream in CRC. Furthermore, our results establish a link between this phenomenon and the size of the tumor mass.

Bioaccessibility and Bioavailability of Diet Polyphenols and Their Modulation of Gut Microbiota.

It is generally accepted that diet-derived polyphenols are bioactive compounds with several potentially beneficial effects on human health. In general, polyphenols have several chemical structures, and the most representative are flavonoids, phenolic acids, and stilbenes. It should be noted that the beneficial effects of polyphenols are closely related to their bioavailability and bioaccessibility, as many of them are rapidly metabolized after administration. Polyphenols-with a protective effect on the gastrointestinal tract-promote the maintenance of the eubiosis of the intestinal microbiota with protective effects against gastric and colon cancers. Thus, the benefits obtained from dietary supplementation of polyphenols would seem to be mediated by the gut microbiota. Taken at certain concentrations, polyphenols have been shown to positively modulate the bacterial component, increasing Lactiplantibacillus spp. and Bifidobacterium spp. involved in the protection of the intestinal barrier and decreasing Clostridium and Fusobacterium, which are negatively associated with human well-being. Based on the diet-microbiota-health axis, this review aims to describe the latest knowledge on the action of dietary polyphenols on human health through the activity of the gut microbiota and discusses micro-encapsulation of polyphenols as a strategy to improve the microbiota.

Plasma-Derived Exosomes from NAFLD Patients Modulate the Cannabinoid Receptors' Expression in Cultured HepaRG Cells.

Exosomes produced by hepatocytes upon lipotoxic insult play a relevant role in pathogenesis of nonalcoholic fatty liver disease (NAFLD), suggesting an inflammatory response by the activation of monocytes and macrophages and accelerating the disease progression. In the pathogenesis of NAFLD and liver fibrosis, the endogenous cannabinoids and their major receptors CB1 and CB2 appear to be highly involved. This study aimed at evaluating the expression of cannabinoids receptors (CB1R and CB2R) in plasma-derived exosomes extracted from patients with NAFLD, as well as investigating the in vitro effects of the circulating exosomes in cultured human HepaRG cells following their introduction into the culture medium. The results demonstrated that plasma-derived exosomes from NAFLD patients are vehicles for the transport of CB1R and are able to modulate CB receptors' expression in HepaRG cells. In particular, circulating exosomes from NAFLD patients are inflammatory drivers for HepaRG cells, acting through CB1R activation and the downregulation of CB2R. Moreover, CB1R upregulation was associated with increased expression levels of PPAR-γ, a well-known mediator of liver tissue injury. In conclusion, this study provides evidence for CB1R transport by exosomes and suggests that the in vitro effects of circulating exosomes from NAFLD patients are mediated by the expression of cannabinoid receptors.

Extension of the shelf-life of fresh pasta using modified atmosphere packaging and bioprotective cultures.

Microbial stability of fresh pasta depends on heat treatment, storage temperature, proper preservatives, and atmosphere packaging. This study aimed at improving the microbial quality, safety, and shelf life of fresh pasta using modified atmosphere composition and packaging with or without the addition of bioprotective cultures (Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium spp., and Bacillus coagulans) into semolina. Three fresh pasta variants were made using (i) the traditional protocol (control), MAP (20:80 CO2:N2), and barrier packaging, (ii) the experimental MAP (40:60 CO2:N2) and barrier packaging, and (iii) the experimental MAP, barrier packaging, and bioprotective cultures. Their effects on physicochemical properties (i.e., content on macro elements, water activity, headspace O2, CO2 concentrations, and mycotoxins), microbiological patterns, protein, and volatile organic compounds (VOC) were investigated at the beginning and the end of the actual or extended shelf-life through traditional and multi-omics approaches. We showed that the gas composition and properties of the packaging material tested in the experimental MAP system, with or without bioprotective cultures, positively affect features of fresh pasta avoiding changes in their main chemical properties, allowing for a storage longer than 120 days under refrigerated conditions. These results support that, although bioprotective cultures were not all able to grow in tested conditions, they can control the spoilage and the associated food-borne microbiota in fresh pasta during storage by their antimicrobials and/or fermentation products synergically. The VOC profiling, based on gas-chromatography mass-spectrometry (GC-MS), highlighted significant differences affected by the different manufacturing and packaging of samples. Therefore, the use of the proposed MAP system and the addition of bioprotective cultures can be considered an industrial helpful strategy to reduce the quality loss during refrigerated storage and to increase the shelf life of fresh pasta for additional 30 days by allowing the economic and environmental benefits spurring innovation in existing production models.

Evaluation of the Effects of the Tritordeum-Based Diet Compared to the Low-FODMAPs Diet on the Fecal Metabolome of IBS-D Patients: A Preliminary Investigation.

Since irritable bowel syndrome (IBS)-a common gastrointestinal (GI) disorder-still lacks effective therapy, a nutritional approach may represent a practical alternative. Different reports demonstrated that a low-fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) diet (LFD) reduces symptoms in IBS with diarrhea (IBS-D) patients, also inducing beneficial pathophysiological and biochemical modifications. More recently, diets with alternative cereals having a different gluten composition, such as tritordeum, have also been considered (TBD). We investigated the impact of TBD and LFD on the fecal metabolome composition in 38 IBS-D patients randomly allocated to the two diets for 12 weeks. Summarily, at baseline, the profile of fecal volatile organic compounds (VOCs) of IBS-D patients was not significantly different in the two groups. After treatment, significant changes were observed in the two groups regarding the VOCs content since some of them increased in the TBD group (namely, decanoic acid), whereas others (i.e., nonanal and ethanol) increased in the LFD one. Further, at baseline, short-chain fatty acids were positively related to inflammation and showed a significant decreasing trend after both diets compared to baseline values (namely, acetic and propanoic acid). Preliminary results from this pilot study suggest a potential positive intervention of TBD and LFD affecting the fecal metabolome composition in IBS-D patients.

Anti-Proliferative and Pro-Apoptotic Effects of Digested Aglianico Grape Pomace Extract in Human Colorectal Cancer Cells.

Grape pomace (GP)-the major by-product of winemaking processes-still contains bioactive molecules with known beneficial properties for human health, such as an antiradical scavenging activity or an antiproliferative activity of tumors. In vitro studies have demonstrated that GP polyphenols specifically influence colon cancer cell proliferation. In addition to previously published work, we tested the phenolic compounds of Aglianico GP following an in vitro simulated gastrointestinal digestion on colorectal cancer cell lines at different degrees of differentiation. Our experiments, using HT29 and SW480 cells, confirmed the anti-proliferative effect of GP gastrointestinal digested extract and provided intriguing insights on the way it influences the cancer cell features (i.e., viability, proliferation, and apoptosis). We observed that Aglianico GP extract showed a great ability to affect cell proliferation and apoptosis. Interestingly, both HT29 and SW480 cells produced a significant increase in Bax, and a significant increase in the Bax/Bcl-2 ratio and caspase-3. The gastrointestinal digested GP extract was previously characterized both for antioxidant activity and phenolic composition. As a result, the TPC and the antioxidant activity reached high values in the Aglianico GP digested extract, and the main compounds assessed by UHPLC-DAD were anthocyanins, phenolic acids, and flavonoids. This work shed light on the use of digested GP extract as a dietary ingredient, a very sustainable source of nutritional compounds with potential health benefits for colon cancer cell proliferation.

Inulin from Globe Artichoke Roots: A Promising Ingredient for the Production of Functional Fresh Pasta.

Globe artichoke roots represent an alternative and sustainable source for inulin extraction and are well-noted for their technological and functional properties. Therefore, the aim of our study was to exploit inulin with high degree of polymerization as a replacement of durum wheat semolina for the production of functional fresh pasta. The effect of increased level of substitution (5, 10, 15%) on cooking, structural, sensory, and nutritional properties were evaluated and compared with a control sample consisting exclusively of durum wheat semolina. Inulin addition caused changes to internal structure as evaluated by scanning electron microscopy. The enriched samples showed a lower swelling index, an increasing cooking time, and values of cooking loss (2.37-3.62%), mainly due to the leaching of inulin into the cooking water. Cooked and raw enriched pasta was significantly darker and firmer than the control, but the sensory attributes were not negatively affected, especially at 5 and 10% of substitution levels. The increase of dietary fiber content in enriched pasta (3.44-12.41 g/100 g) resulted in a significant reduction of glycaemic index (pGI) and starch hydrolysis (HI). After gastrointestinal digestion, inulin-enriched pasta increased prebiotic growth able to significantly reduce E. coli cell density.

Nutraceuticals: Focus on Anti-Inflammatory, Anti-Cancer, Antioxidant Properties in Gastrointestinal Tract.

In recent years, nutraceuticals have gained great popularity, owing to their physiological and potential health effects, such as anti-inflammatory, anti-cancer, antioxidant, and prebiotic effects, and their regulation of lipid metabolism. Since the Mediterranean diet is a nutritionally recommended dietary pattern including high-level consumption of nutraceuticals, this review aimed to summarize the main results obtained by our in vitro and in vivo studies on the effects of the major constituents of the Mediterranean diet (i.e., extra virgin olive oil compounds, polyunsaturated fatty acids, and fruit components). Based on experimental studies, the therapeutic purpose of nutraceuticals depends on their bioavailability, solubility, toxicity, and delivery system. This review provides more in-depth knowledge on the effects linked to nutraceuticals administration on human health, focusing the gastrointestinal tract and suggesting specific dietary components for personalized adjuvant therapies.

A Low Glycemic Index Mediterranean Diet Combined with Aerobic Physical Activity Rearranges the Gut Microbiota Signature in NAFLD Patients.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease, and its prevalence worldwide is increasing. Several studies support the pathophysiological role of the gut-liver axis, where specific signal pathways are finely tuned by intestinal microbiota both in the onset and progression of NAFLD. In the present study, we investigate the impact of different lifestyle interventions on the gut microbiota composition in 109 NAFLD patients randomly allocated to six lifestyle intervention groups: Low Glycemic Index Mediterranean Diet (LGIMD), aerobic activity program (ATFIS_1), combined activity program (ATFIS_2), LGIMD plus ATFIS_1 or ATFIS2 and Control Diet based on CREA-AN (INRAN). The relative abundances of microbial taxa at all taxonomic levels were explored in all the intervention groups and used to cluster samples based on a statistical approach, relying both on the discriminant analysis of principal components (DAPCs) and on a linear regression model. Our analyses reveal important differences when physical activity and the Mediterranean diet are merged as treatment and allow us to identify the most statistically significant taxa linked with liver protection. These findings agree with the decreased 'controlled attenuation parameter' (CAP) detected in the LGIMD-ATFIS_1 group, measured using FibroScan®. In conclusion, our study demonstrates the synergistic effect of lifestyle interventions (diet and/or physical activity programs) on the gut microbiota composition in NAFLD patients.

Effects of Grape Pomace Polyphenols and In Vitro Gastrointestinal Digestion on Antimicrobial Activity: Recovery of Bioactive Compounds.

Grape pomace (GP), a major byproduct obtained from the winemaking process, is characterized by a high amount of phenolic compounds and secondary plant metabolites, with potential beneficial effects on human health. Therefore, GP is a source of bioactive compounds with antioxidant, antimicrobial, and anti-inflammatory activity. As people are paying more attention to sustainability, in this work, we evaluate two different extractions (aqueous and hydroalcoholic) of GP bioactive compounds. In vitro simulated gastrointestinal digestion of the GP extracts was performed to improve the bioavailability and bioaccessibility of polyphenols. The antioxidant activity (ABTS and DPPH assays) and the phenolic characterization of the extracts by UHPLC-DAD were evaluated. The antimicrobial effects of GP antioxidants in combination with a probiotic (Lactiplantibacillus plantarum) on the growth of pathogenic microorganisms (Escherichia coli, Bacillus megaterium, and Listeria monocytogenes) were evaluated. As a result, an increase of antioxidant activity of aqueous GP extracts during the gastrointestinal digestion, and a contextual decrease of hydroalcoholic extracts, were detected. The main compounds assessed by UHPLC-DAD were anthocyanins, phenolic acids, flavonoids, and stilbenes. Despite lower antioxidant activity, due to the presence of antimicrobial active compounds, the aqueous extracts inhibited the growth of pathogens.

Nutritional Improvement of Gluten-Free Breadsticks by Olive Cake Addition and Sourdough Fermentation: How Texture, Sensory, and Aromatic Profile Were Affected?

There is a growing need for gluten-free bakery products with an improved nutritional profile. Currently, gluten-free baked goods deliver low protein, fiber, and mineral content and elevated predicted glycaemic index (pGI). Olive cake (OC), a by-product from virgin olive oil extraction, is an excellent natural source of unsaturated fatty acids, dietary fiber and bioactive molecules, including polyphenols and tocopherols. In this framework, this study aimed at using two selected lactic acid bacteria and a yeast for increasing the antioxidant features and the phenol profile of the gluten-free breadsticks fortified with OC with the perspective of producing a functional food. Control (CTR) samples were prepared and compared with fermented ones (fCTR). Samples were added with either non-fermented OC (nfOC) or fermented for 12 and 20 h (fOC-12 and fOC-20). Our results showed that the predicted glycemic index (pGI) was influenced by both OC addition and sourdough fermentation. In fact, the lowest value of pGI was found in fOC-12, and hydrolysis index and pGI values of samples with OC (fOC-12 and nfOC) were statistically lower than fCTR. Both OC addition and fermentation improved the total phenol content and antioxidant activity of breadsticks. The most pronounced increase in hardness values was observed in the samples subjected to sourdough fermentation as evidenced both from texture profile analysis and sensory evaluation. Moreover, in most cases, the concentration of the detected volatile compounds was reduced by fermentation. Our work highlights the potential of OC to be upcycled in combination with fermentation to produce gluten-free breadsticks with improved nutritional profile, although additional trials are required to enhance textural and sensory profile.

Regulation of Cholesterol Metabolism by Bioactive Components of Soy Proteins: Novel Translational Evidence.

Hypercholesterolemia represents one key pathophysiological factor predisposing to increasing risk of developing cardiovascular disease worldwide. Controlling plasma cholesterol levels and other metabolic risk factors is of paramount importance to prevent the overall burden of disease emerging from cardiovascular-disease-related morbidity and mortality. Dietary cholesterol undergoes micellization and absorption in the small intestine, transport via blood, and uptake in the liver. An important amount of cholesterol originates from hepatic synthesis, and is secreted by the liver into bile together with bile acids (BA) and phospholipids, with all forming micelles and vesicles. In clinical medicine, dietary recommendations play a key role together with pharmacological interventions to counteract the adverse effects of chronic hypercholesterolemia. Bioactive compounds may also be part of initial dietary plans. Specifically, soybean contains proteins and peptides with biological activity on plasma cholesterol levels and this property makes soy proteins a functional food. Here, we discuss how soy proteins modulate lipid metabolism and reduce plasma cholesterol concentrations in humans, with potential outcomes in improving metabolic- and dyslipidemia-related conditions.

Chemical Characterization, Gastrointestinal Motility and Sensory Evaluation of Dark Chocolate: A Nutraceutical Boosting Consumers' Health.

We performed a comprehensive study encompassing chemical characterization and sensory evaluation of two types of dark chocolate, i.e., artisanal (Choco-A) and industrial (Choco-I), as well as an evaluation of onset of gastrointestinal symptoms and gastrointestinal motility in healthy subjects fed with dark chocolate. Proteomic, lipid and metabolite analysis were performed by LC-MS/MS analysis and the total phenol content and antioxidant activity were estimated in both types of chocolate. Fifty healthy volunteers joined the study of the sensory characteristics of both types of chocolate; another 16 subjects underwent the study of gallbladder and gastric emptying by functional ultrasonography and orocecal transit time by lactulose H2-breath test after ingestion of dark chocolate. Identification of polyphenols, amino acids and fatty acids was carried out in both types of chocolate analysed, and results confirmed their richness in polyphenols, amino acid derivatives and fatty acids (FAs) either saturated (stearic, myristic, palmitic, ecosanoic) or unsaturated (oleic and linolenic). For agreeability, Choco-A scored higher than Choco-I for smell, texture, and taste and they did not show significant differences in the gastrointestinal motility. In conclusion as for gastrointestinal motility studies, we report that the ingestion of a small amount of chocolate induced a mild gallbladder, gastric contraction and a fast transit time compared to the test meal in healthy subjects.

Chocolate, "Food of the Gods": History, Science, and Human Health.

Chocolate is well known for its fine flavor, and its history began in ancient times, when the Maya considered chocolate (a cocoa drink prepared with hot water) the "Food of the Gods". The food industry produces many different types of chocolate: in recent years, dark chocolate, in particular, has gained great popularity. Interest in chocolate has grown, owing to its physiological and potential health effects, such as regulation of blood pressure, insulin levels, vascular functions, oxidation processes, prebiotic effects, glucose homeostasis, and lipid metabolism. However, further translational and epidemiologic studies are needed to confirm available results and to evaluate other possible effects related to the consumption of cocoa and chocolate, verifying in humans the effects hitherto demonstrated only in vitro, and suggesting how best to consume (in terms of dose, mode, and time) chocolate in the daily diet.