Dietary polyphenols are garnering attention in the scientific community due to their potential health-beneficial properties and preventative effects against chronic diseases, viz. cardiovascular diseases, diabetes, obesity, and neurodegenerative diseases. Polyphenols are antioxidants that change microbial composition by suppressing pathogenic bacteria and stimulating beneficial bacteria. The interaction of polyphenols with dietary fibers affects their bioaccessibility in the upper and lower parts of the digestive tract. Dietary fibers, polyphenols, their conjugates, and their metabolites modulate microbiome population and diversity. Consuming polyphenol-rich dietary fibers such as pomegranate, cranberry, berries, and tea improves gut health. A complex relationship exists between polyphenol-rich diets and gut microbiota for functioning in human health. In this review, we provide an overview of the interactions of dietary polyphenols, fibers, and gut microbiota, improving the understanding of the functional properties of dietary polyphenols.

The extensive community of gut microbiota significantly influences various biological functions throughout the body, making its characterization a focal point in biomedicine research. Over the past few decades, studies have revealed a potential link between specific gut bacteria, their associated metabolic pathways, and influenza. Bacterial metabolites can communicate directly or indirectly with organs beyond the gut via the intestinal barrier, thereby impacting the physiological functions of the host. As the microbiota increasingly emerges as a 'gut signature' in influenza, gaining a deeper understanding of its role may offer new insights into its pathophysiological relevance and open avenues for novel therapeutic targets. In this Review, we explore the differences in gut microbiota between healthy individuals and those with influenza, the relationship between gut microbiota metabolites and influenza, and potential strategies for preventing and treating influenza through the regulation of gut microbiota and its metabolites, including fecal microbiota transplantation and microecological preparations.

We utilized PubMed and Web of Science as our search databases, employing keywords such as "influenza," "gut microbiota," "traditional Chinese medicine," "metabolites," "prebiotics," "probiotics," and "machine learning" to retrieve studies examining the potential therapeutic connections between the modulation of gut microbiota and its metabolites in the treatment of influenza. The search encompassed literature from the inception of the databases up to December 2023.

Fecal microbiota transplantation (FMT), microbial preparations (probiotics and prebiotics), and traditional Chinese medicine have unique advantages in regulating intestinal microbiota and its metabolites to improve influenza outcomes. The primary mechanism involves increasing beneficial intestinal bacteria such as Bacteroidetes and Bifidobacterium while reducing harmful bacteria such as Proteobacteria. These interventions act directly or indirectly on metabolites such as short-chain fatty acids (SCFAs), amino acids (AAs), bile acids, and monoamines to alleviate lung inflammation, reduce viral load, and exert anti-influenza virus effects.

The gut microbiota and its metabolites have direct or indirect therapeutic effects on influenza, presenting broad research potential for providing new directions in influenza research and offering references for clinical prevention and treatment. Future research should focus on identifying key strains, specific metabolites, and immune regulation mechanisms within the gut microbiota to accurately target microbiota interventions and prevent respiratory viral infections such as influenza.

Intestinal microbiota contributes to host defense against pathogens while avoiding the induction of inflammation in homeostatic conditions, but the mechanism is not fully understood. To investigate the potential role of the bacterial metabolite desaminotyrosine (DAT) in regulating host defense and inflammation, we pretreated mouse bone marrow-derived macrophages (BMDMs) with DAT for 12 hours and then challenged with bacterial lipopolysaccharide (LPS). We found that DAT priming-enhanced type I interferon response while selectively inhibiting proinflammatory interleukin (IL)-6 production after exposure to LPS. This is related to the fact that DAT is a natural antioxidant determined by radical scavenging assay in a cell-free system. DAT-primed cells had increased levels of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) upon LPS stimulation. Countering the increased NADPH by supplementing extra oxidized NADP+ to cells reversed DAT's effect on LPS-induced Il-6 and interferon-stimulated gene expressions. DAT-primed cells also were more resistant to oxidative stress-induced generation of reactive oxygen species and cell death. DAT promoted the production of antimicrobial effector nitric oxide in a cellular redox-dependent manner, leading to enhanced macrophage antimicrobial activity during Salmonella enterica infection. Our data suggest that DAT acts as a host-microbiota crosstalk signal in shaping host immune defense and inflammatory response.

This study evaluated the effects of acerola and guava fruit processing co-products fermented with probiotic Lactobacillus acidophilus LA-05 and Lacticaseibacillus paracasei L-10 on the abundance of different intestinal bacterial groups and microbial metabolic activity during 48 h of in vitro fecal fermentation. Digested fermented fruit co-products increased the relative abundance of beneficial bacterial groups while overall decreasing or maintaining the relative abundance of non-beneficial bacterial groups, suggesting selective stimulatory effects on beneficial bacterial intestinal populations. The fermented co-products stimulated microbial metabolic activity due to decreased pH, sugar consumption, short-chain fatty acid production, phenolic compound and metabolic profile alteration, and high antioxidant capacity during fecal fermentation. Acerola and guava co-products have high nutritional value and bioactive compounds whose fermentation with probiotics improves their potential functionalities. The results show that fermented fruit co-products could induce beneficial changes in the relative abundance of several bacterial groups as well as in the metabolic activity of the human intestinal microbiota. These results highlight their potential as novel and circular candidates for use as synbiotic ingredients.

Obesity is a current global challenge affecting all ages and is characterized by the up-regulated secretion of bioactive factors/pathways which result in adipose tissue inflammation (ATI). Current obesity therapies are mainly focused on lifestyle (diet/nutrition) changes. This is because many chemosynthetic anti-obesogenic medications cause adverse effects like diarrhoea, dyspepsia, and faecal incontinence, among others. As such, it is necessary to appraise the efficacies and mechanisms of action of safer, natural alternatives like plant-sourced compounds, extracts [extractable phenol (EP) and macromolecular antioxidant (MA) extracts], and anti-inflammatory peptides, among others, with a view to providing a unique approach to obesity care. These natural alternatives may constitute potent therapies for ATI linked to obesity. The potential of MA compounds (analysed for the first time in this review) and extracts in ATI and obesity management is elucidated upon, while also highlighting research gaps and future prospects. Furthermore, immune cells, signalling pathways, genes, and adipocyte cytokines play key roles in ATI responses and are targeted in certain therapies. As a result, this review gives an in-depth appraisal of ATI linked to obesity, its causes, mechanisms, and effects of past, present, and future therapies for reversal and alleviation of ATI. Achieving a significant decrease in morbidity and mortality rates attributed to ATI linked to obesity and related comorbidities is possible as research improves our understanding over time.

The aim of this study was to investigate a more practical method for obtaining non-extractable polyphenols (NEPPs) from blue honeysuckle fruit pomace. Three methods, namely acid, alkaline, and enzymatic hydrolysis, were utilized to extract NEPPs. The findings indicated that alkaline hydrolysis was the most effective method for releasing NEPPs, which demonstrated higher levels of total flavonoid content (TFC) and total phenolic content (TPC) from blue honeysuckle fruit pomace. Additionally, higher TPC and TFC levels were related to a stronger antioxidant capacity. Qualitative and quantitative analysis using HPLC-HR-TOF-MS/MS revealed that acid hydrolysis resulted in a greater concentration of certain phenolic acids, while alkaline hydrolysis yielded a higher concentration of flavonoids, and enzymatic hydrolysis produced a wider range of phenolic compositions. Despite the fact that enzymatic hydrolysis is considered a gentler method, the researchers concluded that alkaline hydrolysis was the most appropriate method for obtaining NEPPs from blue honeysuckle fruit pomace.

Seaweed is rich in many unique bioactive compounds such as polyphenols and sulfated polysaccharides that are not found in terrestrial plant. The discovery of numerous biological activities from seaweed has made seaweed an attractive functional food source with the potential to be exploited for human health benefits. During food processing and digestion, cell wall polysaccharide and polyphenols commonly interact, and this may influence the nutritional properties of food. Interactions between cell wall polysaccharide and polyphenols in plant-based system has been extensively studied. However, similar interactions in seaweed have received little attention despite the vast disparity between the structural and chemical composition of plant and seaweed cell wall. This poses a challenge in extracting seaweed bioactive compounds with intact biological properties. This review aims to summarize the cell wall polysaccharide and polyphenols present in brown, red and green seaweed, and current knowledge on their potential interactions. Moreover, this review gives an overview of the gut modulation effect of seaweed polysaccharide and polyphenol.

Dietary fiber (DF) and polyphenols (DP) are typical blood sugar-lowering components, and both play distinct yet interconnected roles in exerting their blood sugar-lowering effects. We comprehensively summarized the single and combined effects of DF and DP on blood glucose homeostasis through regulating the relevant factors in the upper gastrointestinal tract (UGT) and lower gastrointestinal tract (LGT). In the UGT, DF slowed down glucose metabolism by enhancing digesta viscosity and hindering enzyme-substrate interaction. DP primarily targeted enzymes and substrates. When combined, DP enhanced the adsorption capacity of DF for glucose. DF weakened DP's inhibitory effect on enzymes. Both DF and DP disrupted glucose intestinal uptake via physical or genomic modulation, but the co-consumption of DF and DP demonstrated a lower inhibitory effect on glucose uptake than DP alone. In the LGT, DF and DP showed synergistic or antagonistic effects on gut microbiota. Remarkably, whole foods exhibited potent prebiotic effects due to their compound-rich matrix, potentially enhancing glucose homeostasis and expanding dietary options for glucose regulation research.

Inter-individual differences in response to immune checkpoint inhibitors (ICI) remain a major challenge in cancer treatment. The composition of the gut microbiome has been associated with differential ICI outcome, but the underlying molecular mechanisms remain unclear, and therapeutic modulation challenging.

We established an in vivo model to treat C57Bl/6j mice with the type-I interferon (IFN-I)-modulating, bacterial-derived metabolite desaminotyrosine (DAT) to improve ICI therapy. Broad spectrum antibiotics were used to mimic gut microbial dysbiosis and associated ICI resistance. We utilized genetic mouse models to address the role of host IFN-I in DAT-modulated antitumour immunity. Changes in gut microbiota were assessed using 16S-rRNA sequencing analyses.

We found that oral supplementation of mice with the microbial metabolite DAT delays tumour growth and promotes ICI immunotherapy with anti-CTLA-4 or anti-PD-1. DAT-enhanced antitumour immunity was associated with more activated T cells and natural killer cells in the tumour microenvironment and was dependent on host IFN-I signalling. Consistent with this, DAT potently enhanced expansion of antigen-specific T cells following vaccination with an IFN-I-inducing adjuvant. DAT supplementation in mice compensated for the negative effects of broad-spectrum antibiotic-induced dysbiosis on anti-CTLA-4-mediated antitumour immunity. Oral administration of DAT altered the gut microbial composition in mice with increased abundance of bacterial taxa that are associated with beneficial response to ICI immunotherapy.

We introduce the therapeutic use of an IFN-I-modulating bacterial-derived metabolite to overcome resistance to ICI. This approach is a promising strategy particularly for patients with a history of broad-spectrum antibiotic use and associated loss of gut microbial diversity.

Melanoma Research Alliance, Deutsche Forschungsgemeinschaft, German Cancer Aid, Wilhelm Sander Foundation, Novartis Foundation.

Polyphenols, as common components with various functional activities in plants, have become a research hotspot. However, researchers have found that the bioavailability and bioactivity of plant polyphenols is generally low because they are usually in the form of tannins, anthocyanins and glycosides. Polyphenol-rich fermented foods (PFFs) are reported to have better bioavailability and bioactivity than polyphenol-rich foods, because polyphenols are used as substrates during food fermentation and are hydrolyzed into smaller phenolic compounds (such as quercetin, kaempferol, gallic acid, ellagic acid, etc.) with higher bioactivity and bioavailability by polyphenol-associated enzymes (PAEs, e.g., tannases, esterases, phenolic acid decarboxylases and glycosidases). Biotransformation pathways of different polyphenols by PAEs secreted by different microorganisms are different. Meanwhile, polyphenols could also promote the growth of beneficial bacteria during the fermentation process while inhibiting the growth of pathogenic bacteria. Therefore, during the fermentation of PFFs, there must be an interactive relationship between polyphenols and microorganisms. The present study is an integration and analysis of the interaction mechanism between PFFs and microorganisms and is systematically elaborated. The present study will provide some new insights to explore the bioavailability and bioactivity of polyphenol-rich foods and greater exploitation of the availability of functional components (such as polyphenols) in plant-derived foods.

Most of the pertinent research which aims at exploring the therapeutic effects of polyphenols usually misapprehends a large fraction of non-extractable polyphenols due to their poor aqueous-organic solvent extractability. These polymeric polyphenols (i.e., proanthocyanins, hydrolysable tannins and phenolic acids) possess a unique property to adhere to the food matrix polysaccharides and protein sowing to their structural complexity with high glycosylation, degree of polymerization, and plenty of hydroxyl groups. Surprisingly resistance to intestinal absorption does not hinder its bioactivity but accelerates its functionality manifolds due to the colonic microbial catabolism in the gastrointestinal tract, thereby protecting the body from local and systemic inflammatory diseases. This review highlights not only the chemistry, digestion, colonic metabolism of non-extractable polyphenols (NEPP) but also summarises the synergistic effect of matrix-bound NEPP exerting local as well as systemic health benefits.

White wine pomace products (wWPP) represent an innovative strategy as a functional food ingredient to be used as a seasoning both for their technological and functional properties. Nevertheless, the bioactive compounds of wWPP used as a seasoning could be modified during storage. The seasoning in the meat, regardless of the storage method used, modified its phenolic profile and in its bioaccessible fractions, while maintaining a high total antioxidant capacity and total polyphenol content. The contact of the seasoning with the meat can be considered safe as it does not show cytotoxicity in the Caco-2 cells. Additionally, the ability to modulate the cell oxidative stress of the bioaccessible fractions and the potential benefits on microbiota by the colonic fermentation fraction, suggest its potential use as a functional ingredient, without being affected by storage. These results are novel and may help to establish the value of this product as a functional ingredient.

Most processing of the human diet occurs in the small intestine. Metabolites in the small intestine originate from host secretions, plus the ingested exposome1 and microbial transformations. Here we probe the spatiotemporal variation of upper intestinal luminal contents during routine daily digestion in 15 healthy male and female participants. For this, we use a non-invasive, ingestible sampling device to collect and analyse 274 intestinal samples and 60 corresponding stool homogenates by combining five mass spectrometry assays2,3 and 16S rRNA sequencing. We identify 1,909 metabolites, including sulfonolipids and fatty acid esters of hydroxy fatty acids (FAHFA) lipids. We observe that stool and intestinal metabolomes differ dramatically. Food metabolites display trends in dietary biomarkers, unexpected increases in dicarboxylic acids along the intestinal tract and a positive association between luminal keto acids and fruit intake. Diet-derived and microbially linked metabolites account for the largest inter-individual differences. Notably, two individuals who had taken antibiotics within 6 months before sampling show large variation in levels of bioactive FAHFAs and sulfonolipids and other microbially related metabolites. From inter-individual variation, we identify Blautia species as a candidate to be involved in FAHFA metabolism. In conclusion, non-invasive, in vivo sampling of the human small intestine and ascending colon under physiological conditions reveals links between diet, host and microbial metabolism.

Wine pomace (WP) is a major byproduct generated during winemaking, and skin pomace (SKP) comprises one of the most valuable components of WP. Since SKP differs in composition and properties from seed pomace (SDP), precise knowledge of SKP will aid the wine industry in the development of novel, high-value products. The current review summarizes recent advances in research relating to SKP presents a comprehensive description of the generation, composition, and bioactive components, primarily focusing on the biological activities of SKP, including antioxidant, gastrointestinal health promotion, antibacterial, anti-inflammatory, anticancer, and metabolic disease alleviation properties. Currently, the separation and recovery of skins and seeds is an important trend in the wine industry for the disposal of winemaking byproducts. In comparison to SDP, SKP is rich in polyphenols including anthocyanins, flavonols, phenolic acids, stilbenes, and some proanthocyanidins, as well as dietary fiber (DF). These distinctive benefits afford SKP the opportunity for further development and application. Accordingly, the health-promoting mechanism and appropriate application of SKP will be further elucidated in terms of physiological activity, with the progress of biochemical technology and the deepening of related research.

Durum wheat varieties are important sources of nutrients and provide remarkable amounts of phytochemicals. Especially, phenolics, which are mostly located in external layers of grains, have recently gained increased interest due to their high antioxidant power. This study aimed to evaluate the differences in the quality traits and phenolic compounds' concentration (e.g., phenolic acids) of different durum wheat genotypes, namely four Italian durum wheat cultivars and a USA elite variety, in relation to their yield potential and year of release. Phenolic acids were extracted both from wholemeal flour and semolina and analysed through HPLC-DAD analysis. Ferulic acid was the most represented phenolic acid, both in the wholemeal flour (438.3 µg g^-1 dry matter) and in semolina (57.6 µg g^-1 dry matter) across all cultivars, followed by p-coumaric acid, sinapic acid, vanillin, vanillic acid, syringic acid, and p-hydroxybenzoic acid. Among the cultivars, Cappelli showed the highest phenolic acid content, whilst Kronos had the lowest one. Negative correlations occurred between some phenolic acids and morphological and yield-related traits, especially for Nadif and Sfinge varieties. On the contrary, durum wheat genotypes with low yield potential such as Cappelli accumulated higher concentrations of phenolic acids under the same growing conditions, thereby significantly contributing to the health-promoting purposes.

In the past few years, numerous studies have investigated the correlation between polyphenol intake and the prevention of several chronic diseases. Research regarding the global biological fate and bioactivity has been directed to extractable polyphenols that can be found in aqueous-organic extracts, obtained from plant-derived foods. Nevertheless, significant amounts of non-extractable polyphenols, closely associated with the plant cell wall matrix (namely with dietary fibers), are also delivered during digestion, although they are ignored in biological, nutritional, and epidemiological studies. These conjugates have gained the spotlight because they may exert their bioactivities for much longer than extractable polyphenols. Additionally, from a technological food perspective, polyphenols combined with dietary fibers have become increasingly interesting as they could be useful for the food industry to enhance technological functionalities. Non-extractable polyphenols include low molecular weight compounds such as phenolic acids and high molecular weight polymeric compounds such as proanthocyanidins and hydrolysable tannins. Studies concerning these conjugates are scarce, and usually refer to the compositional analysis of individual components rather than to the whole fraction. In this context, the knowledge and exploitation of non-extractable polyphenol-dietary fiber conjugates will be the focus of this review, aiming to access their potential nutritional and biological effect, together with their functional properties.

The health-promoting activities of procyanidin extracts from hawthorn (HPCs) are closely related to their digestive behaviors, absorption, and colonic metabolism, all of which remain unknown for now and thus hinder further exploration. This study aims to explore the dynamic changes of HPCs during in vitro digestion and fermentation, as well as their Caco-2 permeability, focusing mainly on the interaction between gut microbiota and HPCs. The results showed that the digested HPC samples had characteristic absorption peaks at 280 nm, and there were absorption peaks in the stretching vibration zone, including OH and CC on the benzene ring, which suggested that procyanidins were the main components in HPCs after in vitro digestion. Meanwhile, HPCs had the highest stability in the oral phase. However, the total procyanidin content of HPCs decreased during gastrointestinal digestion, and flavan-3-ol dimers and trimers in HPCs are partially degraded into epicatechin. Uptake of epicatechin (4.07 %), procyanidin B2 (2.15 %), and procyanidin B5 (39.44 %) through Caco-2 monolayer was also observed in HPC treatment, while there was still a large portion of procyanidins that was not absorbed. Subsequent fermentation resulted in a decrease in pH along with the production of short-chain fatty acids (SCFAs), mainly due to the degradation and utilization of HPC, as indicated by a reduction of total procyanidins. Furthermore, the HPCs modulated gut microbial populations: down-regulated the abundances of Bacteroides, Fusobacterium, Enterococcus, Parabacteroides, and Bilophila, and up-regulated Escherichia-Shigella, Klebsiella, Turicibacter, Actinobacillus, Roseburia, and Blautia. Ultimately, epicatechin and procyanidin B2, B5 and C1 were converted into phenolic acids through the metabolism of Bacteroides, Sutterella, Butyrobacter and Blautia. 4-ethylbenzoic acid, 4-hydroxyphenylpropionic acid, 3,4-dihydroxyphenyl acetic acid were confirmed as the significant metabolites in the fermentation. These results elucidated the potential mechanisms of HPCs metabolism and their beneficial effects on gut microbiota and colonic phenolic acids production.

The SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2), and the disease it causes (COVID-19), have had a profound impact on global human society and threaten to continue to have such an impact with newly emerging variants. Because of the widespread effects of SARS-CoV-2, understanding how lifestyle choices impact the severity of disease is imperative. This review summarizes evidence for an involvement of chronic, non-resolving inflammation, gut microbiome disruption (dysbiosis with loss of beneficial microorganisms), and impaired viral defenses, all of which are associated with an imbalanced lifestyle, in severe disease manifestations and post-acute sequelae of SARS-CoV-2 (PASC). Humans' physiological propensity for uncontrolled inflammation and severe COVID-19 are briefly contrasted with bats' low propensity for inflammation and their resistance to viral disease. This insight is used to identify positive lifestyle factors with the potential to act in synergy for restoring balance to the immune response and gut microbiome, and thereby protect individuals against severe COVID-19 and PASC. It is proposed that clinicians should consider recommending lifestyle factors, such as stress management, balanced nutrition and physical activity, as preventative measures against severe viral disease and PASC.

Fatigue seriously affects people's work efficiency and quality of life and has become a common health problem in modern societies around the world. The pathophysiology of fatigue is complex and not fully clear. To some degree, interactions between gut microbiota and host may be the cause of fatigue progression. Polyphenols such as tannin, tea polyphenols, curcumin, and soybean isoflavones relieve fatigue significantly. Studies have shown that the gut microbiota is able to convert these active compounds into more active metabolites through intestinal fermentation. However, the mechanism of anti-fatigue polyphenols is currently mainly analyzed from the perspective of antioxidant and anti-inflammatory effects, and changes in gut microbiota are rarely considered. This review focuses on gut microecology and systematically summarizes the latest theoretical and research findings on the interaction of gut microbiota, fatigue, and polyphenols. First, we outline the relationship between gut microbiota and fatigue, including changes in the gut microbiota during fatigue and how they interact with the host. Next, we describe the interactions between the gut microbiota and polyphenols in fatigue treatment (regulation of the gut microbiota by polyphenols and metabolism of polyphenols by the gut microbiota), and how the importance of potential active metabolites (such as urolithin) produced by the decomposition of polyphenols by gut microbiota is emerging. Based on the new perspective of gut microbiota, this review provides interesting insights into the mechanism of polyphenols in fatigue treatment and clarifies the potential of polyphenols as targets for anti-fatigue product development, aiming to provide a useful basis for further research and design.

Flavonoid based proanthocyanidins and cinnamyl alcohol based lignins are chemically complex phenolic oligomers/polymers that are found in food plants. Although structurally very different, these two biopolymers are often not distinguished, for example, in the (quantitative) compositional analysis of cell walls and dietary fiber. Here, we analytically distinguish lignin and proanthocyanidins in dietary fiber samples by using degradative and nondegradative techniques and provide information about their occurrence, abundance, and structural characteristics in seeds of chokeberries, cranberries, raspberries, red currants, and grapes. These data revealed that the seeds of botanically diverse fruits largely differ in terms of their phenolic fiber polymers. The mostly hardened tissue of the seeds is not necessarily based on lignified cell walls. For example, red currant and chokeberry seeds almost exclusively contain proanthocyanidins, and raspberry seeds were clearly lignified (G-H-lignin) but did not contain proanthocyanidins. Our data also allows for estimating the bias of proanthocyanidins on different approaches of lignin analysis.

Food bioactive components, particularly phytochemicals with antioxidant capacity, have been extensively studied over the past two decades. However, as new analytical and molecular biological tools advance, antioxidants related research has undergone significant paradigm shifts. This review is a high-level overview of the evolution of phytochemical antioxidants research. Early research used chemical models to assess the antioxidant capacity of different phytochemicals, which provided important information about the health potential, but the results were overused and misinterpreted despite the lack of biological relevance (Antioxidants v1.0). This led to findings in the anti-inflammatory properties and modulatory effects of cell signaling of phytochemicals (Antioxidants v2.0). Recent advances in the role of diet in modulating gut microbiota have suggested a new phase of food bioactives research along the phytochemicals-gut microbiota-intestinal metabolites-low-grade inflammation-metabolic syndrome axis (Antioxidants v3.0). Polyphenols and carotenoids were discussed in-depth, and future research directions were also provided.

Carotenoids, polyphenols, and minerals (CPMs) are representative bioactive compounds and micronutrients in plant-based foods, showing many potentially positive bioactivities. Bioaccessibility is a prerequisite for bioactivities of CPMs. Cell wall polysaccharides (CWPs) are major structural components of plant cell wall, and they have been proven to affect the bioaccessibility of CPMs in different ways. This review summarizes recent literatures about the effects of CWPs on the bioaccessibility of CPMs and discusses the potential mechanisms. Based on the current findings, CWPs can inhibit the bioaccessibility of CPMs in gastrointestinal tract. The effects of CWPs on the bioaccessibility of polyphenols and minerals mainly attributes to bind between them, while CWPs affect the bioaccessibility of carotenoids by changing the digestive environment. Further, this review overviews the factors (environmental conditions, CWPs properties and CPMs characteristics) affecting the interactions between CWPs and CWPs. This review may help to better design healthy and nutritious foods precisely.

Fruits are the seed-bearing product of plants and have considerable nutritional importance in the human diet. The consumption of fruits is among the dietary strategies recommended for constipation due to its potential effects on the gut microbiota and gut motility. Dietary fiber from fruits has been the subject of research on the impact on gut microbiota, gut motility and constipation, however, fruits also contain other components that impact the intestinal luminal environment that may impact these outcomes including sorbitol and (poly)phenols. This review aims to explore the mechanisms of action and effectiveness of fruits and fruit products on the gut microbiota, gut motility and constipation, with a focus on fiber, sorbitol and (poly)phenols. In vitro, animal and human studies investigating the effects of fruits on gut motility and gut microbiota were sought through electronic database searches, hand searching and consulting with experts. Various fruits have been shown to modify the microbiota in human studies including blueberry powder (lactobacilli, bifidobacteria), prunes (bifidobacteria), kiwi fruit (Bacteroides, Faecalibacterium prausnitzii) and raisins (Ruminococcus, F. prausnitzii). Prunes, raisins and apple fiber isolate have been shown to increase fecal weight in humans, whilst kiwifruit to increase small bowel and fecal water content. Apple fiber isolate, kiwifruit, fig paste, and orange extract have been shown to reduce gut transit time, while prunes have not. There is limited evidence on which fruit components play a predominant role in regulating gut motility and constipation, or whether a synergy of multiple components is responsible for such effects.

Various phenolic compounds of sorghum are effective in the management of abiotic stress (salt, nutrients) and biotic stress (caused by birds, fungi and aphids). The health and industrial application of phenolics is mainly contributed by inherent antioxidant and nutraceutical potential. In a natural environment, plant growth is affected by various biotic and abiotic stresses. In every ecosystem, the presence of a wide range of harmful biological agents (bacteria, fungi, nematodes, mites, and insects) and undesirable environmental factors (drought, salinity, heat, excessive or low rainfall, etc.) may cause a heavy loss in crop productivity. Being sessile during evolution, plants have evolved multiple defense mechanisms against various types of microbial pathogens and environmental stresses. A plant's natural defense system produces some compounds named secondary metabolites, which include phenolics, terpenes, and nitrogen. The phenolic profile of grain sorghum, the least utilized staple crop, is unique, more diverse, and more abundant than in any other common cereal grain. It mainly contains phenolic acids, 3-deoxyanthocyanidins and condensed tannins. Sorghum polyphenols play a major role in plant defense against biotic and abiotic stresses and have many additional health benefits along with various industrial applications. The objective of this review is to discuss the phenolic compounds derived from grain sorghum and describe their role in plant defense, human health, and industrial applications.

Knowledge of the effect of foods on gut microbiota composition and functionality is expanding. To isolate the effect of single foods and/or single nutrients (i.e., fiber, polyphenols), this protocol describes an in vitro batch fermentation procedure to be carried out after an in vitro gastrointestinal digestion. Therefore, this is an extension of the previous protocol described by Brodkorb et al. (2019) for studying in vitro digestion. The current protocol uses an oligotrophic fermentation medium with peptone and a high concentration of fecal inoculum from human fecal samples both to provide the microbiota and as the main source of nutrients for the bacteria. This protocol is recommended for screening work to be performed when many food samples are to be studied. It has been used successfully to study gut microbiota fermentation of different foodstuffs, giving insights into their functionality, community structure or ability to degrade particular substances, which can contribute to the development of personalized nutrition strategies. The procedure does not require a specific level of expertise. The protocol takes 4-6 h for preparation of fermentation tubes and 20 h for incubation.

The wine pomace is the main winery by-products that suppose an economic and environmental problem and their use as a functional ingredient are being increasingly recognized as a good and inexpensive source of bioactive compounds. In this sense, it is known the potential health properties of wine pomace products in the prevention of disorders associated with oxidative stress and inflammation such as endothelial dysfunction, hypertension, hyperglycemia, diabetes, obesity. Those effects are due to the bioactive compounds of wine pomace and the mechanisms concern especially modulation of antioxidant/prooxidant activity, improvement of nitric oxide bioavailability, reduction of pro-inflammatory cytokines and modulation of antioxidant/inflammatory signal pathways. This review mainly summarizes the mechanisms of wine pomace products as modulators of oxidative status involved in cell pathologies as well as their potential therapeutic use for cardiovascular diseases. For this purpose, the review provides an overview of the findings related to the wine pomace bioactive compounds profile, their bioavailability and the action mechanisms for maintaining the redox cell balance involved in health benefits. The review suggests an important role for wine pomace product in cardiovascular diseases prevention and their regular food intake may attenuate the development and progression of comorbidities associated with cardiovascular diseases.

In this work, the acute and subchronic toxicities of desaminotyrosine (DAT) by oral administration in SD rats and its effects on the intestinal microflora were investigated. The acute toxicity test showed that DAT is a low-toxic substance with a LD50 of 3129 mg/kg. The subchronic toxicity test showed that DAT has no toxicity at a low dose (125 mg/kg/day). However, DAT exhibited obvious toxicities to food intake, liver, kidney, and lung at higher dose (250 mg/kg/day and 500 mg/kg/day). DAT inhibited the food intake of rats in a dose-dependent manner. Serum biochemical analysis showed that DAT can increase the serum glucose level of rats. Fecal microbiota analysis showed that DAT treatment can significantly change the intestinal microflora of rats, the dose of 125 mg/kg/day has the most significant effect on the diversity of intestinal microbiota. In daily application, the side effects caused by DAT might be gastrointestinal irritation, weight loss, liver or kidney injury, and blood sugar elevation. Based on our study, the no-observed-adverse-effect level (NOAEL) of DAT is 125 mg/kg BW/day for rats.

It is considered that intestinal barrier dysfunction and systemic endotoxemia drive obesity and its related complications. However, what causes barrier dysfunction remains to be elucidated. Here, we showed that the gut microbiota from high-fat diet (HFD)-fed mice had impaired ability to degrade dietary flavonoids, and in correspondence, the microbial-derived flavonoid metabolite desaminotyrosine (DAT) was reduced. Supplementation of DAT in the drinking water was able to counter the HFD-induced body fat mass accumulation and body weight increment. This is correlated with the role of DAT in maintaining mucosal immune homeostasis to protect barrier integrity. DAT could attenuate dextran sodium sulfate (DSS)-induced mucosal inflammation in a type I interferon signal-dependent manner. Furthermore, intraperitoneal injection of DAT-protected mice from bacterial endotoxin-induced septic shock. Together, we identified DAT as a gut microbiota-derived anti-inflammatory metabolite that functions to modulate local and systemic immune homeostasis. Our data support the notion of dysbiosis being an important driving force of mucosal barrier dysfunction and systemic metabolic complications.

Cell wall polysaccharides (CPSs) and polyphenols are major constituents of the dietary fiber complex in plant-based foods. Their digestion (by gut microbiota) and bioefficacy depend not only on their structure and quantity, but also on their intermolecular interactions. The composition and structure of these compounds vary with their dietary source (i.e., fruit or vegetable of origin) and can be further modified by food processing. Various components and structures of CPSs and polyphenols have been observed to demonstrate common and characteristic behaviors during interactions. However, at a fundamental level, the mechanisms that ultimately drive these interactions are still not fully understood. This review summarizes the current state of knowledge on the internal factors that influence CPS-polyphenol interactions, describes the different ways in which these interactions can be mediated by molecular composition or structure, and introduces the main methods for the analysis of these interactions, as well as the mechanisms involved. Furthermore, a comprehensive overview is provided of recent key findings in the area of CPS-polyphenol interactions. It is becoming clear that these interactions are shaped by a multitude of factors, the most important of which are the physicochemical properties of the partners: their morphology (surface area and porosity/pore shape), chemical composition (sugar ratio, solubility, and non-sugar components), and molecular architecture (molecular weight, degree of esterification, functional groups, and conformation). An improved understanding of the molecular mechanisms that drive interactions between CPSs and polyphenols may allow us to better establish a bridge between food processing and the bioavailability of colonic fermentation products from CPSs and antioxidant polyphenols, which could ultimately lead to the development of new guidelines for the design of healthier and more nutritious foods.

Solid evidence has emerged supporting the role of polyphenols and fibers as gut microbiota modulators. These studies have been limited to the data available in food composition databases, which did not include the food content of non-extractable polyphenols (NEPP). The main objective of this work is to quantify the intake of the different types of dietary polyphenols including NEPP and to evaluate their impact on the composition and activity of the intestinal microbiota.

Cross-sectional descriptive study conducted on a sample of 147 adults with no declared pathologies. Dietary intake has been registered by a semi-quantitative Food Frequency Questionnaire (FFQ) and transformed into extractable (EPP) and NEPP, and dietary fibers based on available databases. Major phylogenetic types of the intestinal microbiota were determined by qPCR and fecal SCFA quantification was performed by gas chromatography.

NEPP account for two-thirds of the total polyphenols intake. A combined analysis by stepwise regression model including all dietary fiber and (poly)phenols has identified hydrolysable (poly)phenol (HPP) intake, as the best predictor of Bacteroides-Prevotella-Porphyromonas group and Bifidobacterium levels in feces. Also, HPPs were positively associated with butyric acid, while insoluble fiber was identified as a predictor of propionic acid in feces.

The intake of macromolecular (poly)phenols could contribute to modulate the gut microbiota by increasing the levels of certain intestinal microorganisms with proven health benefits.

Colorectal cancer (CRC) is one of the most prevalent cancers that threaten people in many countries. It is a multi-factorial chronic disease caused by a combination of genetic and environmental factors, but it is mainly related to lifestyle factors, including diet. Plentiful plant foods and beverages are abundant in polyphenols with antioxidant, anti-atherosclerotic, anti-inflammatory, and anticancer properties. These compounds participate in host nutrition and disease pathology regulation in different ways. Polyphenolic compounds have been used to prevent and inhibit the development and prognosis of cancer, and examples include green tea polyphenol (-)epigallocatechin-3-O-gallate (EGCG), curcumin, and resveratrol. Of course, there are more known and unknown polyphenol compounds that need to be further explored for their anticancer properties. This article focuses on the fact that polyphenols affect the progression of CRC by controlling intestinal inflammation, epigenetics, and the intestinal microbe in the aspects of prevention, treatment, and prognosis.

Although the physiological function of grape extract (GE) has long been recognized, the precise mechanism remains obscure. This study is designed to investigate the effects of GE on metabolism and the association between GE activation of brown adipose tissue (BAT) and the restoration of gut microbiota (GM).

Diet-induced obese mice are used to investigate the function of GE. GE administration increases energy metabolism and prevents obesity. Also, GE restores the dysbiosis of GM by augmenting the observed species, enhancing the Firmicutes-to-Bacteroidetes ratio and increasing the abundance of the Bifidobacteria, Akkermansia, and Clostridia genera. This restoration of GM alters the bile acid (BA) pool in the serum. The abundance of Akkermansia, Clostridium, and Bifidobacterium is negatively correlated with the concentrations of TαMCA, TβMCA, and TCA but is positively correlated with DCA. The changes in BA promoted TGR5 in BAT, which contributed to thermogenesis. The metabolites of GE in blood do not stimulate TGR5 in vitro.

GE stimulates the thermogenesis of BAT through a pathway involving the regulation of GM and BA in diet-induced obese mice. This study reveals the mechanism by which dietary polyphenols promote thermogenesis by regulating BA, which is altered by GM.

Most phenolic compounds and dietary fiber reach intact to the colon. We hypothesized that grape peel powder (GPP), a rich source of these bioactive compounds, modulates inflammatory and oxidative pathways collaborating to attenuate colonic damage in experimental colitis. To determine which bioactive fraction would be responsible for this effect, the aim of this study was to evaluate the effect of dietary supplementation with whole GPP or the isolated bioactive-rich fractions from GPP (extractable polyphenols [EP], dietary fiber and fiber-bound polyphenols [NEP-F], and dietary fiber) in rats with experimental colitis. Colitis was induced by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS) after 15 days of dietary supplementation. EP diet did not reverse the decrease in feed intake and indeed worsened colon shortening and increased spleen weight; however, these effects were not observed for the GPP group, which had polyphenols associated to the matrix besides the extractable ones. Colitis impaired the activity of colonic antioxidant enzymes and increased lipid peroxidation, protein oxidation, nitric oxide (NO) levels, and proinflammatory cytokines in serum and in the colon tissue. GPP restored the activity of antioxidant enzymes and decreased colon oxidation and NO levels. All grape peel fractions reduced the protein expression of the inhibitor of kappa kinase beta and NO levels in colon tissue, but only NEP-F reduced the expression of phosphorylated nuclear factor kappa B and myeloperoxidase activity. Results demonstrated that GPP attenuates inflammatory and oxidative response in TNBS-induced colitis by downregulating the nuclear factor kappa B pathway and upregulating antioxidant enzymes, with NEP-F being the fraction most likely associated to these protective effects.

Water-extracted arabinoxylans (WEAXs) of different varieties and structures have important effects on wheat end products. However, the functional performances of WEAXs, particularly relating to prebiotic potential, are not yet clear. The present study compared the structural features, physicochemical properties, and prebiotic potential of WEAXs from three wheat varieties, which were used as special wheat varieties to make steamed buns, bread flour, and noodles. The results showed that WEAX-1, WEAX-2, and WEAX-3, derived from Jinqiang wheat, American red hard spring wheat, and Australian white wheat, respectively, had different structural properties, gelation properties, and prebiotic potential. WEAX-3 had a low arabinose to xylose (A/X) ratio (0.49), high ferulic acid content (2300 μg/g), and excellent gelation capacity. WEAX-2 had a high A/X ratio (0.62), low ferulic acid content (1300 μg/g), and poor gelation capacity. When fermented with human feces, WEAX-3 significantly increased the numbers of bifidobacteria and lactobacilli and increased the production of short-chain fatty acids (SCFAs), while WEAX-2 had weaker effects on the number of beneficial bacteria and SCFAs production (P < 0.05). The physicochemical properties and prebiotic potential of WEAXs depended strongly on their structural properties. WEAX with a low A/X ratio and a high ferulic acid content showed excellent gelation property and a strong prebiotic potential.

Arabinoxylans (AXs) treated with enzymes, pentosanase (Pn) and glucose oxidase (GOX) not only offer a promising way to improve wheat product quality but also change their prebiotic potentials by modifying the structures of AXs. In the present study, the different crosslinking degrees of water-extracted arabinoxylans (WEAXs) treated with GOX alone or in combination with Pn + GOX were examined. The structural features and candidate prebiotic capabilities were investigated. It was demonstrated that WEAXs treated with 50 μg g-1 (w/w, enzyme/WEAX) GOX and 200 μg g-1 (w/w, enzyme/WEAX) Pn + 400 μg g-1 (w/w, enzyme/WEAX) GOX exhibited weak gel formation, while WEAXs treated with 400 μg g-1 (w/w, enzyme/WEAX) GOX and 25 μg g-1 (w/w, enzyme/WEAX) Pn + 400 μg g-1 (w/w, enzyme/WEAX) GOX formed strong gels. The ferulic acid content was significantly decreased due to the formation of ferulic acid crosslinking in the enzyme-treated WEAXs (p < 0.05). During in vitro fermentation, GOX and Pn + GOX treatments resulted in significantly (p < 0.05) increased amounts of bifidobacteria compared to WEAX alone. Pn + GOX-treated WEAXs had higher (p < 0.05) bifidobacteria populations than WEAXs treated with GOX alone. The bifidobacteria numbers and the SCFAs content of the weak gels were significantly higher than those in the strong gels under the same enzyme action (p < 0.05). These findings suggested that the increased bifidobacteria populations of GOX-treated WEAXs were due to the formation of ferulic acid crosslinking in contrast to a combination of ferulic acid crosslinking and degradation of the xylan backbone as seen in WEAXs treated with Pn + GOX. The reason the weak gels had better prebiotic potential than the corresponding strong gels was their high content of ferulic acid crosslinking.

Inflammatory bowel diseases are characterized by impaired intestinal barrier function. This study aimed to evaluate the effects of grape peel powder (GPP) and its bioactive rich-fractions on the barrier function and colonic injury in a model of colitis induced by 2,4,6 trinitrobenzene sulfonic acid (TNBS). Wistar rats received diets supplemented with either GPP (8%), extractable polyphenols (EP), non-extractable polyphenols-rich fraction (NEP-F), or polyphenols-poor, fiber-rich fraction (F) from grapes at amounts equivalent to the GPP group during 15 days before and for 7 days after colitis induction. NEP-F has decreased the extension of colonic lesion but the other grape peel bioactive fractions did not protect against macroscopic or microscopic colonic damage, EP diet increased macroscopic colonic damage. GPP, EP, and NEP-F reduced claudin-2 mRNA expression, whereas GPP and F fraction increased occludin and ZO-1 mRNA expression. All experimental diets reduced the colitis-triggered increase of MMP-9 mRNA expression. Colitis reduced by 30% the production of cecal short-chain fatty acids (SCFA). GPP and NEP-F completely protected against this effect, whereas F fraction was ineffective. Only GPP and NEP-F were able to decrease the upregulation of GRP94 mRNA triggered by colitis. Dietary fiber seems to reestablish the intestinal barrier function, whereas fiber-bound phenolics were able to restore cecal metabolism to produce beneficial metabolites like SCFA and to reduce the activation of the unfolded protein response.

Grape byproducts are rich sources of polyphenols with powerful antioxidant and health-promoting effects. The impact of supplementing chicken diets with grape byproducts on plasma and thigh meat concentrations of phenolic metabolites was evaluated by analyzing samples by high-performance liquid chromatography quadrupole time of flight mass spectrometry. Chickens were fed three experimental diets: Control diet, Control+8% grape pomace, and Control+0.1% grape seed extract. In plasma, 32 phenolic metabolites were identified, some of which were conjugated catechin/epicatechin metabolites exclusively identified in chickens fed diets enriched in grape byproducts. Also, these chickens showed significantly higher plasmatic concentrations of 21 phenolic metabolites. In thigh meat, 14 phenolic metabolites were identified, but no differences were found between diets. Higher plasmatic tocopherol was found when supplementing diets with grape byproducts, while no changes were observed in meat. Thus, supplementing chicken diets with grape byproducts leads to a significant increase in the circulation of phenolic metabolites and tocopherol.

B-type oligomeric procyanidins in apples constitute an important source of polyphenols in the human diet. Their role in health is not known, although it is suggested that they generate beneficial bioactive compounds upon metabolization by the gut microbiota. During apple processing, procyanidins interact with cell-wall polysaccharides and form stable complexes. These interactions need to be taken into consideration in order to better assess the biological effects of fruit constituents. Our objectives were to evaluate the impact of these interactions on the microbial metabolization of cell walls and procyanidins, and to investigate the potential anti-inflammatory activity of the resulting metabolome, in addition to analyzing the taxonomical changes which the microbiota undergo. In vitro fermentation of three model apple matrices with microbiota from 4 healthy donors showed that the binding of procyanidins to cell-wall polysaccharides, whether covalently or non-covalently, substantially reduced procyanidin degradation. Although cell wall-unbound procyanidins negatively affected carbohydrate fermentation, they generated more hydroxyphenylvaleric acid than bound procyanidins, and increased the abundance of Adlercreutzia and Gordonibacter genera. The best results in terms of production of anti-inflammatory bioactive metabolites were observed from the apple matrix with no bonds between procyanidins and cell wall polysaccharides, although the matrix with non-covalent bonds was not far behind.

Cranberries have multiple health effects but their impact on gut microbiota has not been examined in randomized controlled feeding trials. We evaluated the relationship between the microbiota and cranberries in the context of an animal-based diet. In a randomized, double-blind, cross-over, controlled design trial, 11 healthy adults consumed for 5 days each a control diet (animal-based diet plus 30 g/day placebo powder) and a cranberry diet (animal-based diet plus 30 g/day freeze-dried whole cranberry powder). The animal-based diet included meats, dairy products, and simple sugars. Stool, urine, and blood samples were obtained before and after each intervention phase. As compared to the pre-control diet, control diet modified 46 taxonomic clades, including an increase in the abundance of Firmicutes and decrease in Bacteroidetes. Moreover, it increased bacteria-derived deoxycholic acid and decreased acetate and butyrate in stool. As compared to the post-intervention phase of control diet, the cranberry diet modified 9 taxonomic clades, including a decrease in the abundance of Firmicutes and increase in Bacteroidetes. Further, the cranberry diet attenuated control diet-induced increase in secondary bile acids and decrease in short-chain fatty acids (SCFA), and increased urinary anthocyanins and bacterially derived phenolic acids. No changes were found in fecal trimethylamine and plasma cytokines. In conclusion, an animal-based diet altered the microbiota composition to a less favorable profile, increased carcinogenic bile acids, and decreased beneficial SCFA. Cranberries attenuated the impact of the animal-based diet on microbiota composition, bile acids, and SCFA, evidencing their capacity to modulate the gut microbiota.