This study evaluated the impact of gastrointestinal digestion and colonic fermentation on mango (poly)phenols and their influence on gut microbiota using the dynamic gastrointestinal simulator simgi®. The system was fed with 10 g/day of mango purée for five days, providing 89.5 μmol of phenolic compounds, and inoculated with fecal microbiota from three healthy donors. Samples from the stomach, small intestine, and colon (ascending, transverse and descending) were analysed by UHPLC-HRMS to identify parent compounds and metabolites. Microbial communities were profiled by 16S rRNA gene sequencing, while metabolic activity was assessed through short-chain fatty acid (SCFA) and ammonium (NH₄+) determination. Mango (poly)phenols underwent extensive microbial metabolism, primarily in the colon, generating benzoic, phenylpropanoic, cinnamic acids and hydroxybenzenes, along with a reduction in galloyl derivatives. A progressive and significant increase in the total (poly)phenol content was observed during the feeding period, specifically in the colonic fermentation phase, rising from 66 μmol at the stabilization stage to 174 μmol after 96 h of feeding. Short-term mango feeding modulated microbiota composition, increasing the relative abundance of beneficial taxa such as Bifidobacterium spp., across colonic compartments. Regarding metabolic activity, a marked increase in butyric acid production was observed in the ascending colon, rising from 6 mM to 47 mM. In parallel, a significant reduction in ammonium concentration was detected across all colonic compartments during the feeding period, decreasing from 275 to 51 mg/L by the end of the experiment. Overall, these findings confirm that mango (poly)phenols promoted bioactive metabolites and supported a healthier gut environment.

One of the key limitations of current dietary assessment methodologies is to adjust the food portion size. In this study, we propose a Deep Learning (DL) approach to estimate the weight of individual pieces of commonly consumed fruits (apple, pear, orange and banana) from single-view RGB (Red, Green and Blue) photographs. The DL models developed in this study were based on convolutional neural networks trained on an ad-hoc dataset of 48,960 photographs including a wide and representative range of fruit piece weights, reflecting typical market variability and reducing the likelihood of encountering out-of-range samples. The photographs of apples (n=12,960), pears (n=17,208), oranges (n=8,712) and bananas (n=10,080) were taken under different conditions. The DL models were evaluated in terms of saliency maps and regression metrics. Mean Absolute Error (MAE) values indicated that the measurements in the DL models developed would be out —as a mean— by no more than 20.57 g (apple), 19.25 g (pear), 28.31 g (orange) and 21.93 g (bananas) between the predicted and the observed values, quite acceptable considering the variability in fruit weights and photographic conditions. The four DL models developed in this study predict fruit weight from a simple photograph, requiring only a visible €1 coin as a reference, without considering the background. This approach is feasible because our DL models were trained on diverse images across different angles, distances, lighting conditions, tablecloths and dish types, allowing the models to generalise well in real-world contexts.

Nutritional supplementation is emerging as a promising strategy to support clinical management of early Alzheimer's disease (AD), partly through modulation of the intestinal microbiome via the microbiota-gut-brain axis. This study investigated the impact of Fortasyn Connect (Souvenaid®), a multinutrient formulation, on gut microbiota using a dual approach: i) a dynamic gastrointestinal simulator (simgi®) inoculated with feces from AD patients, and ii) an observational study involving early-stage AD patients (n = 22) receiving or not the supplement. The in vitro model provided a direct, host-independent assessment of microbiota responses, showing increased Bifidobacterium and Lactobacillus levels, alongside enhanced short-chain fatty acid (SCFA) production. In patients, supplementation was associated with higher fecal abundance of Bifidobacterium and Christensenellaceae, reduced inflammatory markers (calprotectin and myeloperoxidase), and increased butyrate levels. Fecal lipidomic and proteomic analyses indicated improved lipid digestion, increased secretory IgA, and modulation of host proteins linked to gut-brain homeostasis. Systemically, elevated levels of iron, folate, and vitamin B12 were also observed. For the first time, this study shows that supplements such as Fortasyn Connect can beneficially modulate the gut ecosystem and related immune-metabolic pathways in early AD, thereby targeting disease-relevant mechanisms through the gut-brain axis, in the context of aging.

Mango (Mangifera indica L.) comprises a rich source of (poly)phenolic compounds, predominantly galloyl-derived (poly)phenols. While a portion of these bioactive compounds are metabolised and absorbed in the upper gastrointestinal tract, the remainder reach the colon, where they are subjected to microbial catabolism. This study investigated the colonic transformation of mango (poly)phenols and their impact on gut microbiota. Ileal fluids (IFs), collected from six ileostomists before and for an 8 h period after mango consumption, were subjected to ex vivo fecal fermentation to simulate colonic conditions. Pre-fermentation (0 h) and post-fermentation (2, 6 and 24 h) samples were analysed by UHPLC-HRMS for changes in (poly)phenol composition, by GC-FID for microbial metabolism (short-chain fatty acids (SCFAs)), and 16S rRNA gene sequencing to assess changes in gut microbiota. A total of 48 phenolics were identified in the fermented IF samples, before and after mango consumption. The main compounds included benzoic acids, hydroxybenzenes and galloyl derivatives, with high interindividual variability. Among the microbial catabolites, 3,4,5-trihydroxybenzoic acid, 3,5-dihydroxy-4-methoxybenzoic acid and 1,3,5-trihydroxybenzene emerged as possible discriminants of fermented mango IFs. The IF matrix, rather than mango (poly)phenols, significantly influenced gut bacterial diversity (p < 0.05, alpha-diversity) and increased microbial SCFAs production (mainly acetic, butyric and propionic acids). A significant positive correlation (p < 0.05) was found between characteristic catabolites in fermented mango IF samples and some commensal and healthy-related bacteria such as Bifidobacterium spp. Overall, despite high interindividual variability, the results suggest that IF-enriched with mango (poly)phenols undergo substantial microbial catabolism and positively impact on the gut microbial environment. The study was registered at clinicaltrials.gov as NCT06182540.

Sulfites are widely used in the wine industry, but their human health effects remain debated. This study is the first to investigate the interaction between wine sulfites and gut microbiota under simulated gastrointestinal conditions. Using the simgi model, red and synthetic wines─with and without SO2 (200 mg/L)─underwent gastrointestinal digestion and colonic fermentation with fecal microbiota from three healthy donors (n = 3). SO2-treated wines slightly modified gut microbiota composition, decreasing beneficial bacteria like Bacteroides and Ruminococcus, while increasing Coprococcus and pro-inflammatory Escherichia/Shigella, although the overall microbiome of each individual seems to condition its resilience toward SO2. These effects were partially mitigated in red wine, suggesting a protective role of wine polyphenols. Additionally, SO2 treatment in red wines enhanced phenolic metabolism at the gut level, increasing low-molecular-weight phenolic compounds, such as valerolactones, bioavailable in the small intestine and colon. For instance, 5-(3',4'-dihydroxyphenyl)-γ-valerolactone concentrations were consistently higher in SO2-treated red wine (0.86-1.28 mg/L) than in the untreated wine (<0.78 mg/L) after 6 h of fermentation. This pioneering study reveals a complex interplay between sulfites, wine components, and gut microbiota, with potential health implications, especially for sulfite-sensitive individuals.

Enzymatic pea protein hydrolysates offer potential health benefits because of their content of bioactive peptides, which have been released from the protein by the action of proteases. This study examined how the degree of hydrolysis (DH) of pea protein with trypsin influences physicochemical parameters and antioxidant capacity of the resulting hydrolysates. The molecular weight (MW) distribution of a pea protein isolate and its hydrolysates at the DHs of 2%, 5%, 8%, and 12% was determined using size-exclusion chromatography. Surface hydrophobicity was evaluated by two fluorescent probe assays, namely 8-anilino-1-naphthalenesulfonic acid (ANS) and cis -parinaric acid (CPA). Antioxidant potential was assessed as ABTS •+ scavenging capacity, oxygen radical absorbance capacity (ORAC FL ), antioxidant capacity of water-soluble and lipid-soluble compounds in the photochemiluminescence assay (PCL-ACW and PCL-ACL, respectively), and the ability to inhibit the oxidation of β-carotene-linoleic acid emulsion. With increasing DH, the contribution of fractions with MWs of 2–4 kDa and 4–7 kDa in the hydrolysates increased. However, the relative content of peptides with MWs less than 2 kDa remained below 10% in all of them. The ABTS •+ scavenging capacity and ORAC FL also increased with DH, and the highest values, 0.111 and 0.320 mmol Trolox equivalent/g, respectively, were obtained for the hydrolysate at a DH 12%. Surface hydrophobicity increased only to DH 5%. Hydrolysates at DHs of 8% and 12% were characterized by gradually lower values. The trend of surface hydrophobicity changes was consistent with that of PCL-ACL. Additionally, principal component analysis showed an association between surface hydrophobicity and antioxidant capacity in the model emulsion. Overall, tryptic pea protein hydrolysates had improved antioxidant properties compared to the isolate, and the degree of hydrolysis was a parameter that allowed optimizing these properties under different conditions of antioxidant action.

Estimation of wine components' intake (polyphenols, alcohol, etc.) through Food Frequency Questionnaires (FFQs) may be particularly inaccurate. This paper reports the development of a deep learning (DL) method to determine red wine volume from single-view images, along with its application in a consumer study developed via a web service. The DL model demonstrated satisfactory performance not only in a daily lifelike images dataset (mean absolute error = 10 mL), but also in a real images dataset that was generated through the consumer study (mean absolute error = 26 mL). Based on the data reported by the participants in the consumer study (n = 38), average red wine volume in a glass was 114 +/- 33 mL, which represents an intake of 137-342 mg of total polyphenols, 11.2 g of alcohol, 0.342 g of sugars, among other components. Therefore, the proposed method constitutes a diet-monitoring tool of substantial utility in the accurate assessment of wine components' intake.

This work seeks to generate new knowledge about the mechanisms underlying the protective effects of cranberry against urinary tract infections (UTI). Using Caco-2 cells grown in Transwell inserts as an intestinal barrier model, we found that a cranberry-derived digestive fluid (containing 135 +/- 5 mg of phenolic compounds/L) increased transepithelial electrical resistance with respect to control (Delta TEER = 54.5 Omega cm2) and decreased FITC-dextran paracellular transport by about 30%, which was related to the upregulation of the gene expression of tight junction (TJ) proteins (i.e., occludin, zonula occludens-1 [ZO-1], and claudin-2) (similar to 3-4-fold change with respect to control for claudin-2 and similar to 2-3-fold for occludin and ZO-1). Similar protective effects, albeit to a lesser extent, were observed when Caco-2 cells were previously infected with uropathogenic Escherichia coli (UPEC). In a urinary barrier model comprising T24 cells grown in Transwell inserts and either noninfected or UPEC-infected, treatments with the cranberry-derived phenolic metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and phenylacetic acid (PAA) (250 mu M) also promoted favorable changes in barrier integrity and permeability. In this line, incubation of noninfected T24 cells with these metabolites induced positive regulatory effects on claudin-2 and ZO-1 expression (similar to 3.5- and similar to 2-fold change with respect to control for DOPAC and similar to 1.5- and >2-fold change with respect to control for PAA, respectively). Overall, these results suggest that the protective action of cranberry polyphenols against UTI might involve molecular mechanisms related to the integrity and functionality of the urothelium and intestinal epithelium.

The aim of this study was to investigate whether microbial-derived phenolic acids, 3,4-dihydroxyphenylacetic (DHPA), protocatechuic acid (PCA), and dihydrocaffeic acid (DHCFA) and their conjugated forms (DHCFA 3-O-sulfate and DHCFA 3-O-β-D-glucuronide), exhibit protective effects against neuroinflammation and oxidative stress. Experiments were performed on human neuronal SH-SY5Y cells stimulated with bacterial lipopolysaccharide (LPS) and tert-butyl hydroperoxide (tBHP). Anti-inflammatory activity in terms of pro-inflammatory cytokine production was also evaluated in LPS-stimulated RAW 264.7 macrophages as a reactive microglial model. Treatment of the SH-SY5Y cells with the free phenolic acids, as well as with the conjugated metabolites, at physiologically concentrations (1, 10 and 50 μM), resulted in increased cell viability of LPS- and tBHP-stimulated cells. Phenolic metabolites and, especially, the conjugated derivatives also protected neuronal cells through significant attenuation of inflammation by decreasing ROS levels. Furthermore, the conjugated and microbial-derived phenolic metabolites significantly inhibited the secretion of proinflammatory cytokines (TNF-α, IL-6, and IL-8) in LPS-stimulated macrophages. Among the phenolic metabolites tested, different efficacies were observed, with the glucuronide form standing out. Overall, these results suggest, for the first time, that conjugated derivatives of phenolic acids seem to be more effective at protecting neurons from inflammation damage and oxidative stress. Further in vivo studies are warranted.

Dietary polyphenols and in particular bioavailable metabolites resulting from gut microbiota transformations appear to have beneficial effects in situations of impaired cognition, combatting memory deficits in acute pathological models of neurodegeneration. Modifications to blood flow may underlie the effects of these molecules and although some such metabolites cross the blood-brain barrier, their targets and electrophysiological effects remain unknown. Hence, we explored the systemic and direct effects of protochatechuic acid (PCA) on electrical activity in the hippocampus and cortex of anesthetized female rats, recording evoked and spontaneous high-density field potentials (FPs) to mathematically derive pathway-specific FP generators. We found transient and sustained effects of PCA on evoked activity in the CA1 field, including paradoxical actions on excitatory transmission that depend on the route of administration. Systemic delivery of PCA altered the ongoing activity of some FP generators, albeit with marked inter-animal variation. Interestingly, PCA induced the detachment of infraslow cortico-hippocampal activities over a scale of minutes. These results point to direct actions of polyphenols on cell and network electrical activity, some of which reflect non-specific actions. Thus, dietary-derived polyphenols appear to fulfill neuromodulatory roles, encouraging the search for additional targets to better guide their use in preventing brain pathologies.

This study investigates the effects of moderate red wine consumption on the clinical status and symptomatology of patients with Ulcerative Colitis (UC), including the study of the oral and intestinal microbiome. A case control intervention study in UC patients was designed. Intervention patients (n = 5) consumed red wine (250 mL/day) for four weeks whereas control patients (n = 5) did not. Moderate wine consumption significantly (p < 0.05) improved the parameters related to serum iron, and particularly, faecal calprotectin, considered one of the most used parameters in the diagnosis and remission of IBD. Similarly, the intervention with wine alleviated intestinal symptoms evaluated by the IBDQ-32 questionnaire and, consequently, increased the patient's subjective quality of life appreciation. The metagenomic analysis of the microbial populations present in saliva and faeces indicated a lower bacterial diversity in UC patients compared to healthy individuals. Moderate consumption of red wine seemed to balance the proportions of microbial communities and could promote a microbial profile more similar to that observed in healthy individuals. Finally, analysis of faecal metabolites (i.e., phenolic acids and SCFAs) indicated a non-significant increase (p > 0.05) for the UC patients that consumed wine.

Gut microbiota represents a diverse and dynamic population of microorganisms harbouring the gastrointestinal tract, which influences host health and disease. Bacterial colonization of the gastrointestinal tract begins at birth and changes throughout life, with age being one of the conditioning factors for its vitality. Aging is also a primary risk factor for most neurodegenerative diseases. Among them, Alzheimer ' s disease (AD) is probably the one where its association with a state of dysbiosis of the gut microbiota has been most studied. In particular, intestinal microbial-derived metabolites have been associated with b-amyloid formation and brain amyloid deposition, tau phosphorylation, as well as neuroinflammation in AD patients. Moreover, it has been suggested that some oral bacteria increase the risk of developing AD. However, the causal connections among microbiome, amyloid-tau interaction, and neurodegeneration need to be addressed. This paper summarizes the emerging evidence in the literature regarding the link between the oral and gut microbiome and neurodegeneration with a focus on AD. Taxonomic features of bacteria as well as microbial functional alterations associated with AD biomarkers are the main points reviewed. Data from clinical studies as well as the link between microbiome and clinical determinants of AD are particularly emphasized. Further, relationships between gut microbiota and age-dependent epigenetic changes and other neurological disorders are also described. Together, all this evidence suggests that, in some sense, gut microbiota can be seen as an additional hallmark of human aging and neurodegeneration. This article is part of a Special Issue entitled: SI: The Molecular Bases of Tauopathies. (c) 2023 The Author(s). Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).

Silk fibroin nanoparticles (SFN) are interesting drug delivery systems due to their high load capacity and low toxicity. The aim of this study was to reveal how SFN load red wine polyphenols (RWP), and to assess their protective effect during the early stages of digestion by using the dynamic gastrointestinal simulator (simgi (R)) under physiological conditions. RWP-SFN were prepared by incubation of SFN in red wine and recovered by centrifugation. The obtained nanoparticles (particle size of 194.4 +/- 2.1 nm and a Zeta potential of-22.7 +/- 0.1 mV) showed a significant polyphenol loading content (7386.59 +/- 1018.28 mu g/g) with a high encapsulation efficiency (66.66 +/- 2.58%). They were highly stable during their passage through the digestive tract, being the activity of RWP highly preserved. This data paves the way for future developments of SFN as stabilizers with a wide range of applications in the field of food additives.

Dietary polyphenols have beneficial effects in situations of impaired cognition in acute models of neurodegeneration. The possibility that they may have a direct effect on the electrical activity of neuronal populations has not been tested. We explored the electrophysiological action of protocatechuic acid (PCA) on CA1 pyramidal cells ex vivo and network activity in anesthetized female rats using pathway-specific field potential (FP) generators obtained from laminar FPs in cortex and hippocampus. Whole-cell recordings from CA1 pyramidal cells revealed increased synaptic potentials, particularly in response to basal dendritic excitation, while the associated evoked firing was significantly reduced. This counterintuitive result was attributed to a marked increase of the rheobase and voltage threshold, indicating a decreased ability to generate spikes in response to depolarizing current. Systemic administration of PCA only slightly altered the ongoing activity of some FP generators, although it produced a striking disengagement of infraslow activities between the cortex and hippocampus on a scale of minutes. To our knowledge, this is the first report showing the direct action of a dietary polyphenol on electrical activity, performing neuromodulatory roles at both the cellular and network levels.

This study investigates food matrix effects during the co-digestion of red wine with different nutrients, including glucose and whey proteins, as well as olive oil lipids and cholesterol by using the gastrointestinal dynamic simulator simgi®. Co-digestion with red wine led to a reduction of glucose bioaccessibility and of α-lactalbumin gastric digestibility. In relation to lipids, the co-digestion with red wine tended to increase the percentage of bioaccessible monoglycerides, although significant differences were not found. Interestingly, co-digestion with red wine tended to reduce cholesterol bioaccessibility, which could be related to the decrease in bile salt content observed in the micellar phase. Furthermore, co-digestion with the food models modified wine polyphenols profiles during gastrointestinal digestion, including their bioaccessible and non-bioaccessible fractions. At colonic level, combined intake of wine and each food model affected colonic microbiota composition and functionality. In particular, wine digestion favoured intestinal health-related taxa, and the co-digestion of wine and food models favoured production of total short and medium chain fatty acids, especially butyric and pentanoic acids. Finally, cytotoxicity of the colonic-digested samples towards human colon adenocarcinoma cells was found to be significantly lower for the Wine and Wine+Lipid models than for the Lipid model and the control.

Resumen Este estudio surge de la necesidad de nuevas metodologías que permitan cuantificar el consumo de vino con mayor precisión, para posteriormente utilizar esta información en estudios observacionales de alimentación-salud y estudios de intervención de dieta. Se ha desarrollado un algoritmo basado en un método de “aprendizaje profundo”, que permite determinar el volumen de vino en una copa/vaso a partir de una fotografía, y se ha validado en un estudio de consumidores realizado a través de una aplicación web. La aplicación del modelo a imágenes “cuasi-reales” y a imágenes "reales" (obtenidas a partir del estudio de consumidores), ha mostrado una precisión satisfactoria con un error absoluto medio (MAE) de 10 mL y 26 mL, respectivamente. En relación a las pautas de consumo de vino observadas en el estudio de consumidores (n=38), el volumen medio de vino tinto servido en una copa fue de 114±33 mL, sin estar condicionado por factores como el sexo del consumidor, el momento de consumo, el tipo de vino, o el formato de copa/vaso. En síntesis, el sistema de aprendizaje profundo desarrollado junto con la aplicación web, constituyen una herramienta de gran valor para la estimación precisa del volumen de vino consumido diariamente, así como las pautas de su consumo, de gran utilidad para estudios poblacionales.

Beer is a source of bioactive compounds, mainly polyphenols, which can reach the large intestine and interact with colonic microbiota. However, the effects of beer consumption in the gastrointestinal function have scarcely been studied. This paper reports, for the first time, the in vitro digestion of beer and its impact on intestinal microbiota metabolism. Three commercial beers of different styles were subjected to gastrointestinal digestion using the simgi® model, and the digested fluids were further fermented in triplicate with faecal microbiota from a healthy volunteer. The effect of digested beer on human gut microbiota was evaluated in terms of microbial metabolism (short-chain fatty acids (SCFAs) and ammonium ion), microbial diversity and bacterial populations (plate counting and 16S rRNA gene sequencing). Monitoring beer polyphenols through the different digestion phases showed their extensive metabolism, mainly at the colonic stage. In addition, a higher abundance of taxa related to gut health, especially Bacteroides, Bifidobacterium, Mitsuokella and Succinilasticum at the genus level, and the Ruminococcaceae and Prevotellaceae families were found in the presence of beers. Regarding microbial metabolism, beer feeding significantly increased microbial SCFA production (mainly butyric acid) and decreased ammonium content. Overall, these results evidence the positive actions of moderate beer consumption on the metabolic activity of colonic microbiota, suggesting that the raw materials and brewing methods used may affect the beer gut effects.

Grape pomace (GP) is a winemaking by-product particularly rich in (poly)phenols and dietary fiber, which are the main active compounds responsible for its health-promoting effects. These components and their metabolites generated at the intestinal level have been shown to play an important role in promoting health locally and systemically. This review focuses on the potential bioactivities of GP in the intestinal environment, which is the primary site of interaction for food components and their biological activities. These mechanisms include (i) regulation of nutrient digestion and absorption (GP has been shown to inhibit enzymes such as α-amylase and α-glucosidase, protease, and lipase, which can help to reduce blood glucose and lipid levels, and to modulate the expression of intestinal transporters, which can also help to regulate nutrient absorption); (ii) modulation of gut hormone levels and satiety (GP stimulates GLP-1, PYY, CCK, ghrelin, and GIP release, which can help to regulate appetite and satiety); (iii) reinforcement of gut morphology (including the crypt-villi structures, which can improve nutrient absorption and protect against intestinal damage); (iv) protection of intestinal barrier integrity (through tight junctions and paracellular transport); (v) modulation of inflammation and oxidative stress triggered by NF-kB and Nrf2 signaling pathways; and (vi) impact on gut microbiota composition and functionality (leading to increased production of SCFAs and decreased production of LPS). The overall effect of GP within the gut environment reinforces the intestinal function as the first line of defense against multiple disorders, including those impacting cardiometabolic health. Future research on GP's health-promoting properties should consider connections between the gut and other organs, including the gut-heart axis, gut-brain axis, gut-skin axis, and oral-gut axis. Further exploration of these connections, including more human studies, will solidify GP's role as a cardiometabolic health-promoting ingredient and contribute to the prevention and management of cardiovascular diseases.