大豆活性组分和肠道菌群相互作用研究进展

目前食品组分与肠道菌群的相互作用及其对健康的影响已成为膳食与健康领域的研究热点。存在于动物体内的肠道菌群对大豆活性组分的分解代谢、转化吸收有着重要作用,大豆活性组分在体内肠道菌群作用下发生生物转化,导致其结构改变,从而形成新的活性成分,进而影响人体健康。同时,大豆活性组分的肠道菌群代谢产物又能够调节肠道菌群结构、保护肠黏膜屏障、维护肠道微生态平衡。本文对大豆活性组分如何在菌群作用下进行有效生物转化、肠道菌群在外源组分的扰动下如何进行菌群结构和丰度调整以及大豆组分的菌群代谢产物对人的健康影响等方面进行了综述,以期为深入研究大豆活性成分对人体健康作用的机理提供参考。     

Dietary Amino Acids and the Gut‐Microbiome‐Immune Axis: Physiological Metabolism and Therapeutic Prospects

Dietary amino acids (AAs) are not only absorbed and metabolized by enterocytes but also available to the microbiota in the gut in mammals. In addition to serving as the materials for protein synthesis, AAs can act as precursors for numerous metabolic end products in reactions involving the intestinal mucosa and microbiota. After penetrating the epithelial barrier, microbial metabolites can enter and accumulate in the host circulatory system, where they are sensed by immune cells and then elicit a wide range of biological functions via different receptors and mechanisms. Some intestinal bacteria can also synthesize certain AAs, implying that the exchange of AAs between hosts and microorganisms is bidirectional. Changes in AA composition and abundance can affect AA‐metabolizing bacterial communities and modulate macrophages and dendritic cells via toll‐like receptors (TLRs), autoinducer‐2 (AI‐2), and NOD‐like receptors (NLRs), and also regulate the gut‐microbiome‐immune axis via aryl hydrocarbon receptor (AhR), serotonin/5‐hydroxytryptamine (5‐HT), and other signaling pathways, all of which play critical roles in regulating the intestinal mucosal immunity and microbiota directly or indirectly, contributing to intestinal homeostasis. Therefore, the current findings of the effects of certain functional AAs on the gut‐microbiome‐immune axis are reviewed, illustrating signaling pathways of tryptophan (Trp), glutamine (Gln), methionine (Met), and branched‐chain AAs (BCAAs) in the intestinal barrier and regarding immunity via crosstalk with their receptors or ligands. These findings have shed light on the clinical applications of dietary AAs in improving gut microbiota and mucosal immunity, therefore benefiting the gut as well as local and systemic health.     

Influence of Intestinal Microbiota on the Catabolism of Flavonoids in Mice

Although in vitro studies have shown that flavonoids are metabolized into phenolic acids by the gut microbiota, the biotransformation of flavonoids by intestinal microbiota is seldom studied in vivo. In this study, we investigated the impact of the gut microbiota on the biotransformation of 3 subclasses of flavonoids (flavonols, flavones, and flavanones). The ability of intestinal microbiota to convert flavonoids was confirmed with an in vitro fermentation model using mouse gut microflora. Simultaneously, purified flavonoids were administered to control and antibiotic‐treated mice by gavage, and the metabolism of these flavonoids was evaluated. p‐Hydroxyphenylacetic acid, protocatechuic acid, p‐hydroxybenzoic acid, vanillic acid, hydrocaffeic acid, coumaric acid, and 3‐(4‐hydroxyphenyl)propionic acid were detected in the serum samples from the control mice after flavonoid consumption. The serum flavonoid concentrations were similar in both groups, whereas the phenolic metabolite concentrations were lower in the antibiotic‐treated mice than in the control mice. We detected markedly higher flavonoids excretion in the feces and urine of the antibiotic‐treated mice compared to the controls. Moreover, phenolic metabolites were upregulated in the control mice. These results suggest that the intestinal microbiota are not necessary for the absorption of flavonoids, but are required for their transformation.     

Regulation of the intestinal tight junction by natural polyphenols: A mechanistic perspective

Impairment of the epithelial barrier function is closely linked to the pathogenesis of various gastrointestinal diseases, food allergies, type I diabetes, and other systematic diseases. Plant-derived polyphenols are natural secondary metabolites and exert various physiological benefits, including anti-inflammatory, anti-oxidative, anti-carcinogenic, and anti-aging effects. Recent studies also show the role of plant polyphenols in regulation of the intestinal barrier and prevention of intestinal inflammatory diseases. Here we summarize the regulatory pathways and mediators linking polyphenols to their beneficial effects on tight junction and gut epithelial barrier functions, and provide useful information about using polyphenols as nutraceuticals for intestinal diseases.     

体外发酵对柑橘黄酮的生物转化及功能活性研究进展

柑橘黄酮是一类主要存在于柑橘属植物果实外皮中的次生代谢物,具有多种生理功能,可预防和改善与氧化应激、炎症、癌细胞增殖和脂质积累等造成的健康问题。然而,柑橘黄酮普遍存在溶解性不高、稳定性较差、生物利用度低等问题。通过体外发酵技术对柑橘黄酮的特定结构进行修饰,能一定程度上改善其生物利用度并增强功能活性。该文从柑橘黄酮的结构与分类、参与体外发酵的微生物及酶种类、柑橘黄酮的体外转化过程及代谢产物等多个方面详细阐述了生物催化剂对柑橘黄酮的定向结构修饰作用,并总结了生物转化对柑橘黄酮产物抗氧化、抗炎、抑制癌细胞增殖、抗病毒、降脂等多种功能活性的影响,以期为柑橘黄酮的生物转化研究及新型功能食品开发提供理论依据。     

Combination of freeze drying and molecular inclusion techniques improves the bioaccessibility of microencapsulated anthocyanins from black rice (Oryza sativa L.) and lavender (Lavandula angustifolia L.) essential oils in a model food system

Black rice and lavender are promising sources of bioactives, in terms of anthocyanins and essential oils. Their bioaccessibility were improved by microencapsulation, followed by mixing in order to benefit both from colour and flavour, along with radical scavenging and biological properties. The mixed powder showed a satisfactory anthocyanins of 2.55 mg g⁻¹ DW, leading to a radical scavenging activity of 65.14 mmol g⁻¹ DW. The powder displayed an inhibitory effect against α-glucosidase (~49%) and α-amylase (39%), respectively, with a controlled release in intestinal environment. To further examine the functional properties, the powder was added to a food model system. During storage, a release in anthocyanins and flavonoids were found, leading to an increase in radical scavenging activity. The sensorial analysis showed that supplemented biscuits were appreciated for colour and lavender aroma. The obtained results were promising in tailoring the health benefits of secondary metabolites, underutilised in human’s nutrition due to their low stability and bioavailability.     

Characterization of Metabolic Pathways and Absorption of Sea Cucumber Saponins,Holothurin A and Echinoside A,in Vitro and in Vivo

Sea cucumber saponins (SCSs) exhibit a wide spectrum of bioactivities, but their metabolic characteristics are not well elucidated. In this study, the metabolism of holothurin A (HA) and echinoside A (EA), 2 major saponins in sea cucumber, by gut microflora were investigated. First, we conducted an in vitro study, where in the SCSs were incubated with intestinal microflora and the metabolites were detected by high pressure liquid chromatography–high resolution mass spectrometry. We also conducted an in vivo study on rats, where in the intestinal contents, serum, urine, and feces were collected and evaluated after oral administration of SCSs. In the in vitro study, we identified 6 deglycosylated metabolites of HA and EA, assigned M1‐M6. In the in vivo study, we found all the deglycosylated metabolites in the intestinal contents after oral administration, and both the metabolites and their prototype components could be absorbed. Four metabolites were identified in the serum, 6 in the urine, and 4 in the feces. The saponins with different structures showed different absorption characteristics in rats. According to our results, deglycosylation is the main intestinal microflora‐mediated metabolic pathway for SCSs, and both the SCSs and deglycosylated metabolites can be absorbed by intestine. This study improves the understanding of the metabolism of HA and EA by gut flora, which will be useful for further analysis of the bioactivity mechanism of SCSs.     

The Bioavailability,Transport, and Bioactivity of Dietary Flavonoids: A Review from a Historical Perspective

Flavonoids are plant‐derived dietary components with a substantial impact on human health. Research has expanded massively since it began in the 1930s, and the complex pathways involved in bioavailability of flavonoids in the human body are now well understood. In recent years, it has been appreciated that the gut microbiome plays a major role in flavonoid action, but much progress still needs to be made in this area. Since the first publications on the health effects of flavonoids, their action is understood to protect against various stresses, but the mechanism of action has evolved from the now debunked simple direct antioxidant hypothesis into an understanding of the complex effects on molecular targets and enzymes in specific cell types. This review traces the development of the field over the past 8 decades, and indicates the current state of the art, and how it was reached. Future recommendations based on this historical analysis are (a) to focus on key areas of flavonoid action, (b) to perform human intervention studies focusing on bioavailability and protective effects, and (c) to carry out cellular in vitro experiments using appropriate cells together with the chemical form of the flavonoid found at the site of action; this could be the native form of compounds found in the food for studies on digestion and the intestine, the conjugated metabolites found in the blood after absorption in the small intestine for studies on cells, or the chemical forms found in the blood and tissues after catabolism by the gut microbiota.     

Modulation of the human gut microbiota by phenolics and phenolic fiber‐rich foods

The gut microbiota plays a prominent role in human health. Alterations in the gut microbiota are linked to the development of chronic diseases such as obesity, inflammatory bowel disease, metabolic syndrome, and certain cancers. We know that diet plays an important role to initiate, shape, and modulate the gut microbiota. Long‐term dietary patterns are shown to be closely related with the gut microbiota enterotypes, specifically long‐term consumption of carbohydrates (related to Prevotella abundance) or a diet rich in protein and animal fats (correlated to Bacteroides). Short‐term consumption of solely animal‐ or plant‐based diets have rapid and reproducible modulatory effects on the human gut microbiota. These alterations in microbiota profile by dietary alterations can be due to impact of different dietary macronutrients, carbohydrates, protein, and fat, which have diverse modulatory effects on gut microbial composition. Food‐derived phenolics, which encompass structural variants of flavonoids, hydroxybenzoic acids, hydroxycinnamic acids, coumarins, stilbenes, ellagitannins, and lignans can modify the gut microbiota. Gut microbes have been shown to act on dietary fibers and phenolics to produce functional metabolites that contribute to gut health. Here, we discuss recent studies on the impacts of phenolics and phenolic fiber‐rich foods on the human gut microbiota and provide an insight into potential synergistic roles between their bacterial metabolic products in the regulation of the intestinal microbiota.     

黄酮类化合物吸收代谢及其对胃肠道功能影响的研究进展

黄酮类化合物是一大类重要的植物次生代谢产物,既具有良好的药理活性,也是重要的营养因子。它的吸收、代谢及排泄等均在胃肠道内完成,在胃肠道中发挥多种生理功能,包括抗氧化、抗炎、抗癌、调节肠道菌群等。因此,近年来已有大量研究报道了有关黄酮类化合物在消化道中的消化、吸收规律,并针对黄酮类化合物的功能活性将其开发用于针对消化道疾病的各种新型食品、药品、保健品中。本文就近年来黄酮类化合物在胃肠道中代谢规律及其对人类健康效应相关研究进行了综述,旨在为黄酮类化合物在预防肠道疾病中的应用及作为新型功能性食品的开发提供参考。     

Beneficial health characteristics of native and hydrolysed konjac (Amorphophallus konjac) glucomannan

The impact of ingesting glucomannans on health is not limited to colonic‐focused fermentation into short‐chain fatty acids (SCFAs), which might have some local health benefits; it also helps in treating disease states and enhancing the body's immune system, both within the gut and in/on other parts of the body. The local and systemic roles of hydrolysed glucomannans, especially konjac glucomannans, in the mouth, oesophagus, stomach, small intestine, large intestine, gut‐associated lymphoid tissue (GALT), skin and vagina, are highlighted. Therapeutic applications are discussed. © 2015 Society of Chemical Industry     

益生乳酸菌与肠道菌群稳态

肠道是个复杂的微生态系统,不仅包含宿主细胞和各种营养物质,还包含数以万计的微生物。这些肠道微生物与宿主健康息息相关,对宿主营养、代谢、生理和免疫均有影响,肠道菌群发生紊乱还会引起各种疾病。大量临床试验表明,益生乳酸菌可通过调节宿主肠道菌群稳态治疗或缓解多种疾病。本文作者描述了失衡指数（DI）、微生物平衡指数（MBI）和微生物失衡指数（MDI）这3种量化肠道菌群稳态的计算方法及其应用,阐述了益生乳酸菌对肥胖和健康宿主肠道菌群稳态的影响,指出益生乳酸菌可能通过与肠道中病原菌竞争结合位点或分泌物质抑制病原菌,分泌代谢物为肠道中有益共生菌提供适宜生长繁殖的环境和制造“假想敌”刺激宿主免疫系统应答等方式维持宿主肠道菌群稳态,并讨论了维持宿主肠道菌群稳态的重要性。同时还综述了益生乳酸菌研究现状,指出益生乳酸菌的研究要做到个性化,不仅要考虑研究人群个体差异,还要考虑菌株之间的差异。     

乳铁蛋白对肠道屏障保护作用的研究进展

完整的肠道屏障是维持肠道健康的先行和必要条件。乳铁蛋白因其具有多种生物活性而备受推崇。近年来,国内外大量研究报道了乳铁蛋白通过修复肠黏膜、调节免疫功能和肠道菌群等来维持肠道稳态。该研究主要对乳铁蛋白的生物学特性、乳铁蛋白对肠屏障的作用以及乳铁蛋白的应用进行了综述。     

Effects of the oral administration of the products derived from milk fermentation by kefir microflora on immune stimulation

Nutritional status has a major impact on the immune system. Probiotic effects ascribed to fermented dairy products arise not only from whole microorganisms but also from metabolites (peptides, exopolysaccharides) produced during the fermentation. We recently demonstrated the immunomodulating capacity of kefir in a murine model. We now aimed at studying the immunomodulating capacity in vivo of the products derived from milk fermentation by kefir microflora (PMFKM) on the gut. BALB/c mice received the PMFKM for 2, 5 or 7 consecutive days. IgA+ and IgG+ cells were determined on histological slices of the small and large intestine. IL-4, IL-6, IL-10, IL-12, IFNgamma and TNFalpha were determined in the gut, intestinal fluid and blood serum. IL-6 was also determined in the supernatant of a primary culture of small intestine epithelial cells challenged with PMFKM. PMFKM up-regulated IL-6 secretion, necessary for B-cell terminal differentiation to IgA secreting cells in the gut lamina propria. There was an increase in the number of IgA+ cells in the small and large intestine. The increase in the number of IgA+ cells was accompanied by an increase in the number of IL-4+, IL-10+ and IL-6+ cells in the small intestine. Effects of PMFKM in the large intestine were less widely apparent than the ones observed at the small intestine lamina propria. All cytokines that increased in the small intestine lamina propria, also did so in blood serum, reflecting here the immunostimulation achieved in the gut mucosa. We observed that the PMFKM induced a mucosal response and it was able to up and down regulate it for protective immunity, maintaining the intestinal homeostasis, enhancing the IgA production at both the small and large intestine level. The opportunity exists then to manipulate the constituents of the lumen of the intestine through dietary means, thereby enhancing the health status of the host.     

Dietary compounds and traditional Chinese medicine ameliorate type 2 diabetes by modulating gut microbiota

Abstract

Diabetes mellitus (DM) and its complications are major public health concerns which strongly influence the quality of humans’ life. Modification of gut microbiota has been widely used for the management of diabetes. In this review, the relationship between diabetes and gut microbiota, as well as the effects of different dietary components and traditional Chinese medicine (TCM) on gut microflora are summarized. Dietary compounds and TCM possessing bioactive components (fiber and phytochemicals) first change the composition of gut microbiota (inhibiting pathogens and promoting the beneficial bacteria growth) and then influence the production of their metabolites, which would further modify the intestinal environment through inhibiting the production of detrimental compounds (such as lipopolysaccharide, hydrogen sulfide, indol, etc.). Importantly, metabolites (short chain fatty acids and other bioactive components) fermented/degraded by gut microbiota can target multiple pathways in intestine, liver, pancreas, etc., resulting in the improvement of gut health, glycemic control, lipids profile, insulin resistance and inflammation. Furthermore, understanding the interaction between different dietary components and gut microbiota, as well as underlying mechanisms would help design different diet formula for the management of diabetes. Further researches could focus on the combination of different dietary components for preventing and treating diabetes, based on the principle of “multiple components against multiple targets” from the perspective of gut microbiota.     

Bovine milk oligosaccharides decrease gut permeability and improve inflammation and microbial dysbiosis in diet-induced obese mice

Obesity is characterized by altered gut homeostasis, including dysbiosis and increased gut permeability closely linked to the development of metabolic disorders. Milk oligosaccharides are complex sugars that selectively enhance the growth of specific beneficial bacteria in the gastrointestinal tract and could be used as prebiotics. The aim of the study was to demonstrate the effects of bovine milk oligosaccharides (BMO) and Bifidobacterium longum ssp. infantis (B. infantis) on restoring diet-induced obesity intestinal microbiota and barrier function defects in mice. Male C57/BL6 mice were fed a Western diet (WD, 40% fat/kcal) or normal chow (C, 14% fat/kcal) for 7 wk. During the final 2 wk of the study, the diet of a subgroup of WD-fed mice was supplemented with BMO (7% wt/wt). Weekly gavage of B. infantis was performed in all mice starting at wk 3, yet B. infantis could not be detected in any luminal contents when mice were killed. Supplementation of the WD with BMO normalized the cecal and colonic microbiota with increased abundance of Lactobacillus compared with both WD and C mice and restoration of Allobaculum and Ruminococcus levels to that of C mice. The BMO supplementation reduced WD-induced increase in paracellular and transcellular flux in the large intestine as well as mRNA levels of the inflammatory marker tumor necrosis factor α. In conclusion, BMO are promising prebiotics to modulate gut microbiota and intestinal barrier function for enhanced health.     

多酚通过肠道菌群调节能量代谢研究进展

多酚是一类植物次生代谢产物,广泛存在于人类膳食中,一般可分为3大类：酚酸类、聚合单宁类和黄酮类。多酚以及其被肠道菌群代谢的产物,能选择性调节肠道中易感微生物的生长,选择性的促进有益菌群(如乳酸菌)生长,抑制有害菌的增殖,也即引发肠道微生态的改变。这种改变对宿主产生重要影响,对宿主能量代谢的影响可能通过如下实现：1)肠道内微生物数量和种类的变化,改变微生物代谢及产酶的种类和数量;2)多酚代谢产物还可与细菌细胞表面作用,抑制酶的活性,从而影响能量代谢,减少脂肪沉积;3)多酚通过干预人体肠道菌群调整能量代谢,为预防和治疗肥胖及相关性疾病提供了新的研究思路。本文对多酚调整肠道菌群从而影响肥胖发生的作用机制进行了综述。     

Flavonoids alter P-gp expression in intestinal epithelial cells in vitro and in vivo

Flavonoids are secondary plant metabolites included in our diet but are also provided in a growing number of supplements. They are suggested to interact with intestinal transport systems including phospho-glycoprotein (P-gp) which mediates the efflux of a variety of xenobiotics back into the gut lumen. In human intestinal Caco-2 cells, we tested the effects of 14 different flavonoids on P-gp expression in vitro. Protein expression levels were quantified by Western blotting, flow cytometry, and real-time PCR. Except apigenin, all flavonoids at concentrations of 10 microM increased P-gp expression in Western blotting experiments when cells were exposed to the compounds over 4 wk. Flavone was one of the most effective P-gp inducers in Caco-2 cells and its effects were, therefore, also assessed for changes in P-gp in vivo in the gastrointestinal tract of C57BL/6 mice. P-gp expression was significantly increased by flavone (400 mg/kg body weight x day over 4 wk) in the small intestine but not in the colon which displayed intrinsically the highest expression level. In conclusion, the increase in P-gp expression caused by flavonoids in intestinal epithelial cells in vitro and also in vivo may serve as an adaptation and defense mechanism limiting the entry of lipophilic xenobiotics into the organism.     

Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites

Flavan-3-ols, occurring in monomeric, as well as in oligomeric and polymeric forms (also known as condensed tannins or proanthocyanidins), are among the most abundant and bioactive dietary polyphenols, but their in vivo health effects in humans may be limited because of their recognition as xenobiotics. Bioavailability of flavan-3-ols is largely influenced by their degree of polymerization; while monomers are readily absorbed in the small intestine, oligomers and polymers need to be biotransformed by the colonic microbiota before absorption. Therefore, phenolic metabolites, rather than the original high molecular weight compounds found in foods, may be responsible for the health effects derived from flavan-3-ol consumption. Flavan-3-ol phenolic metabolites differ in structure, amount and excretion site. Phase II or tissular metabolites derived from the small intestine and hepatic metabolism are presented as conjugated derivatives (glucuronic acid or sulfate esters, methyl ether, or their combined forms) of monomeric flavan-3-ols and are preferentially eliminated in the bile, whereas microbial metabolites are rather simple conjugated lactones and phenolic acids that are largely excreted in urine. Although the colon is seen as an important organ for the metabolism of flavan-3-ols, the microbial catabolic pathways of these compounds are still under consideration, partly due to the lack of identification of bacteria with such capacity. Studies performed with synthesized or isolated phase II conjugated metabolites have revealed that they could have an effect beyond their antioxidant properties, by interacting with signalling pathways implicated in important processes involved in the development of diseases, among other bioactivities. However, the biological properties of microbe-derived metabolites in their actual conjugated forms remain largely unknown. Currently, there is an increasing interest in their effects on intestinal infections, inflammatory intestinal diseases and overall gut health. The present review will give an insight into the metabolism and microbial biotransformation of flavan-3-ols, including tentative catabolic pathways and aspects related to the identification of bacteria with the ability to catabolize these kinds of polyphenols. Also, the in vitro bioactivities of phase II and microbial phenolic metabolites will be covered in detail.     

Influence of functional food components on gut health

Intestinal epithelial cells (IECs) lining the gastrointestinal tract establish a barrier between external environments and the internal milieu. An intact intestinal barrier maintains gut health and overall good health of the body by preventing from tissue injury, pathogen infection and disease development. When the intestinal barrier function is compromised, bacterial translocation can occur. Our gut microbiota also plays a fundamentally important role in health, for example, by maintaining intestinal barrier integrity, metabolism and modulating the immune system, etc. Any disruption of gut microbiota composition (also termed dysbiosis) can lead to various pathological conditions. In short, intestinal barrier and gut microbiota are two crucial factors affecting gut health. The gastrointestinal tract is a complex environment exposed to many dietary components and commensal bacteria. Dietary components are increasingly recognized to play various beneficial roles beyond basic nutrition, resulting in the development of the functional food concepts. Various dietary modifiers, including the consumption of live bacteria (probiotics) and ingestible food constituents such as prebiotics, as well as polyphenols or synbiotics (combinations of probiotics and prebiotics) are the most well characterized dietary bioactive compounds and have been demonstrated to beneficially impact the gut health and the overall well-being of the host. In this review we depict the roles of intestinal epithelium and gut microbiota in mucosal defence responses and the influence of certain functional food components on the modulation of gut health, with a particular focus on probiotics, prebiotics and polyphenols.