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.     

The Gut Microbiota and Its Metabolites,Novel Targets for Treating and Preventing Non‐Alcoholic Fatty Liver Disease

Non‐alcoholic fatty liver disease (NAFLD) is one of the most prevalent metabolic disorders worldwide, along with obesity and type 2 diabetes. NAFLD involves a series of liver abnormalities from simple hepatic steatosis to non‐alcoholic steatohepatitis, which can ultimately lead to liver cirrhosis and cancer. The gut–liver axis plays an important role in the development of NAFLD, which depends mainly on regulation of the gut microbiota and its bacterial products. These intestinal bacterial species and their metabolites, including bile acids, tryptophan catabolites, and branched‐chain amino acids, regulate adipose tissue and intestinal homeostasis and contribute to the pathogenesis of NAFLD/non‐alcoholic steatohepatitis. In this review, the current evidence regarding the key role of the gut microbiota and its metabolites in the pathogenesis and development of NAFLD is highlighted, and the advances in the progression and applied prospects of gut microbiota‐targeted dietary and exercise therapies is also discussed.     

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.     

益生菌对Ⅱ型糖尿病影响的研究进展

肠道菌群在调节机体新陈代谢、维持人体健康和疾病发生中起着重要作用。近年来随着对肠道微生物研究的深入,人们发现肠道菌群与代谢综合征、过敏、神经退行性疾病等疾病的发生和发展密切相关。目前,肠道菌群与人体健康之间的联系成为研究热点,但肠道菌群与这些疾病的关系以及相应的发病机制尚不清楚。对肠道菌群结构和代谢物的16S rRNA及宏基因组进行分析,揭示了肠道菌群组成与糖尿病之间的相关性。益生菌作为人体肠道共生菌中一类特殊的菌群,可以调节胃肠道稳态、营养物质代谢和能量平衡。因此,以肠道微生物为靶点缓解或治疗糖尿病有其独特的优势。本文总结了益生菌在糖尿病防治中的研究进展,为糖尿病的相关研究提供参考。     

微生物-肠-脑轴对肥胖调控的研究进展

肥胖已经成为一种全球性的流行病,严重威害人们的健康和生命,预防和治疗肥胖是世界各国面临的重大公共卫生挑战。越来越多的研究发现肥胖的发生和发展与肠道菌群有着密切的关系,肠道菌群与肥胖之间的调控机制成为研究的热点。微生物-肠-脑轴是肠道菌群参与的肠道和大脑的双向信息交流系统,是大脑和肠道功能相互整合、相互调节的途径。近年国内外的研究表明,微生物-肠-脑轴在肥胖调控方面具有重要的贡献,很多物质通过该途径发挥降脂减肥功能。本文综述了肥胖的严峻现状、微生物-肠-脑轴的组成以及调控肥胖的机制,以期为治疗肥胖等代谢疾病提供思路,也为一些降脂物质的机理研究提供了方向。     

Dietary strategies may influence human nerves and emotions by regulating intestinal microbiota: an interesting hypothesis

The human body hosts enormous diversity of microbiota. Recently, the importance of microbial communities to host physiology has been recognised. Evidence is now emerging that the bidirectional communication between the central nervous system and gastrointestinal tract may affect human nerves, cognition and behaviour through the gut-brain axis (GBA). Although the connection between enteropathy and neurological diseases has been found, it now seems intestinal microorganisms represent the direct mediator of psychopathology. The interactions between host neurological function and intestinal microbiota suggested dietary is a possible way to alleviate psychopathological and neurodegenerative diseases. This review discusses the possible effect of intestinal microbiota on the changes of nerves and emotions in human brain. Maintaining healthy diet strategies should be an important part of preventing neurological diseases and psychopathologies caused by systemic metabolic changes. We hope to provide a novel insight for the design of dietary therapies from the perspective of GBA.     

Maternal High-Fat Diet Results in Long-Term Sex-Specific Alterations to Metabolic and Gut Microbial Diurnal Oscillations in Adult Offspring

Scope: Circadian rhythms profoundly impact metabolism and the gut microbiota. A maternal high-fat diet (HFD) exerts effects on the metabolic syndrome of adult offspring in a sex-specific manner, the underlying mechanisms, however, remain unclear. Methods and results: Female mice are fed an HFD and raise their offspring on a standard chow diet until 24 weeks. The glucose tolerance, insulin sensitivity, and diurnal rhythms of serum metabolic profiles are assessed in male and female adult offspring. Simultaneously, 16S rRNA is applied to characterize gut microbiota diurnal rhythms. The study finds that maternal HFD tends to deteriorate glucose tolerance and impairs insulin sensitivity in male offspring, but not female offspring, which can be associated with the circadian alterations of serum metabolic profiles in male offspring. As expected, maternal HFD sex-specifically alters diurnal rhythms of the gut microbiota, which exhibits putative associations with metabolic profiles in males. Conclusions: The present study identifies the critical role of gut microbiota diurnal rhythms in triggering sex-biased metabolic diurnal rhythms in response to maternal HFD, at least in part. As early life may be a critical window for preventing metabolic diseases, these findings provide the basis for developing chronobiology applications targeting the gut microbiota to combat early metabolic alterations, especially in males.     

High-protein compound yogurt with quinoa improved clinical features and metabolism of high-fat diet–induced nonalcoholic fatty liver disease in mice

Gut microbiota dysbiosis plays a crucial role in the occurrence and progression of nonalcoholic fatty liver disease (NAFLD), which may be influenced by nutritional supplementation. Quinoa, a type of pseudocereal, has gained prominence due to its high nutritional value and diverse applications. This study aimed to determine whether yogurt containing quinoa can ameliorate NAFLD and alleviate metabolic disorders by protecting against the divergence of gut microbiota. Our findings suggested that quinoa yogurt could significantly reduce the body weight gain and fat tissue weight of high-fat diet (HFD)–fed obese mice. In addition, quinoa yogurt significantly reduced liver steatosis and enhanced glucose homeostasis and insulin sensitivity. Additional research indicates that quinoa yogurt can reduce the levels of proinflammatory cytokines (i.e., tumor necrosis factor α, IL-1β, and IL-6) and inhibit endotoxemia and systemic inflammation. The characteristics of the gut microbiota were then determined by analyzing 16S rRNA. In addition, we discovered that the gut microbiota was disturbed by HFD consumption. Particularly, intestinal probiotics and beneficial intestinal secretions were increased, leading to the expression of glucagon-like peptide-1 in the colon, contributing to NAFLD. Furthermore, endotoxemia and systemic inflammation in HFD-fed mice were restored to the level of control mice when they were fed yogurt and quinoa. Therefore, yogurt containing quinoa can effectively alleviate NAFLD symptoms and may exert its effects via microbiome-gut-liver axis mechanisms. According to some research, the role of the enteric-liver axis may also influence metabolic disorders to reduce the development of NAFLD.     

脑-肠轴与精神疾病肠道微生物的研究进展

人体肠道拥有大量且种类丰富的微生物群,在机体的多项生理过程中扮演着重要的角色。近年来越来越多的研究表明,肠道菌群可以通过脑-肠轴来调节机体大脑的发育和行为,从而对自闭症谱系障碍、精神分裂症、抑郁症、焦虑症等精神类疾病具有良好的防治作用。本文在阐述脑-肠轴的双向调控机制基础上,总结了与各种精神疾病直接相关因素的变化和可能机制,并进一步归纳了近年来国内外关于各类精神疾病中肠道微生物改变的研究进展,以期为上述精神类疾病患者通过早期益生菌干预治疗的研究提供新的思路和理论参考。     

益生菌对高血压影响的研究进展

肠道菌群在代谢综合征、心血管疾病和结直肠癌等疾病中的研究已经成为焦点,但是肠道微生物与这些疾 病的因果关系以及相应的致病机制尚不清楚。通过分析肠道菌群结构、组成以及代谢活动的变化对高血压的影响, 能够揭示肠道以及肠道微生物的活动与高血压之间的相关性。益生菌是对机体健康产生有益作用的活的微生物,可 以调节肠道微生态的平衡以及肠道微生物的代谢活动,从而对高血压的调节产生影响,进而为以肠道微生物为靶点 干预治疗高血压疾病提供理论参考,同时也为疾病的干预治疗提供新的途径和方法。     

Addressing the gut microbiome and implications for obesity

Identification of the gut microbiota as an environmental factor that modulates obesity and metabolic diseases has provided the medical and functional food industry with new targets to treat metabolic diseases. However, only limited knowledge about the mechanisms by which the gut microbiota contributes to these lifestyle diseases are known. The gut microbiota is involved in energy harvest from the diet, modulation of endocrine signalling, and promoting metabolic inflammation. This review will discuss how the gut microbiota is altered in obesity, some of the mechanisms by which it promotes disease development, and how pre- and probiotics may be used to improve metabolic diseases.     

Interactions of tea polyphenols with intestinal microbiota and their implication for anti-obesity

Tea polyphenols (TP) are the main components in tea. Studies in vitro have shown they have significant biological activity; however, the results are inconsistent with experiments in vivo. For the low bioavailability, most TP are thought to remain in the gut and metabolized by intestinal bacteria. In the gut, the unabsorbed TP are metabolized to a variety of derivative products by intestinal flora, which may accumulate to exert beneficial effects. Numerous studies have shown that TP can inhibit obesity and its related metabolism disorders effectively. Meanwhile, it has demonstrated that TP and their derivatives may modulate intestinal micro-ecology. The understanding of the interaction between TP and intestinal microbiota will allow us to better evaluate the contribution of microbial metabolites of TP to anti-obesity activity. This review showed implications for the use of TP as functional food with potential therapeutic utility against obesity by modulating intestinal microbiota, contributing to the improvement of human health. © 2019 Society of Chemical Industry     

油脂营养成分及其对肠道健康影响的研究进展北大核心CSCD

油脂是人体最主要的营养物质之一,其消化吸收主要发生在肠道,而肠道内存在种类繁多的菌群,可以直接参与人体的消化吸收、脂质代谢、能量供应等。油脂的消化吸收可能与多种代谢紊乱和肠道疾病、糖尿病、肥胖等慢性疾病存在联系,而食用油脂摄入不平衡会影响肠道菌群组成和代谢,破坏肠道稳态,进而可能导致上述疾病的发生。综述了油脂的脂肪酸组成、功能性伴随成分及其对人体健康的影响,分析了近年来油脂对肠道菌群组成及其代谢产物影响的研究,并对未来的研究方向进行了展望,这对进一步开展油脂营养特性及其对肠道健康影响的研究以及合理膳食保障人体健康具有积极意义。     

Interplay between gut microbiota,its metabolites and human metabolism: Dissecting cause from consequence

BackgroundAlterations in gut microbiota composition and bacterial metabolites have been increasingly recognized to affect host metabolism and are at the basis of metabolic diseases such as obesity and type 2 diabetes (DM2). Intestinal enteroendocrine cells (EEC's) sense gut luminal content and accordingly secrete hormones that modulate glucose and lipid metabolism and affect satiety. It has become evident that microbial metabolic products significantly affect EEC function.Scope and approachIn this review, we will discuss current insights in the role of the gut microbiota and its metabolites in development of obesity and DM2 and elaborate on interventions that modulate EEC action.Key findings and conclusionsStudies including fecal transplantation and Roux-en-Y gastric bypass (RYGB) in humans and animal models suggest that the gut microbiota and its metabolites causally contribute to development of obesity and DM2. Emerging evidence suggests that the gut microbiota and its metabolites can modulate secretion of EEC hormones that regulate appetite and insulin secretion. Dispersed intestinal expression and low abundance make EEC's difficult to study. Since current intestinal sampling methods in humans are mostly limited to the colon, this leaves a large part of EEC function understudied. It would therefore be relevant to develop means to extend sampling methods throughout to entire GI tract.     

肠道菌群对饮食诱导的高尿酸血症的调控研究进展

高尿酸血症是一种人体血尿酸水平异常升高的代谢性疾病,由嘌呤代谢紊乱和/或尿酸排泄障碍导致,其中高果糖和高嘌呤的饮食具有明显的高尿酸诱导效应。近年来,研究发现高尿酸血症与肠道菌群存在密切关系,患者存在肠道菌群紊乱、有益菌属丰度下降的现象。合理的膳食及益生菌摄入可有效调节肠道菌群,维持其稳态,并促进肠道嘌呤和尿酸代谢,提示肠道菌群是未来预防高尿酸血症的靶点。本文概述了高尿酸血症的发病特征和机制、饮食对高尿酸血症的诱导、高尿酸血症与肠道菌群的关联性,以及肠道菌群调控高尿酸血症的策略,以期为未来开发诊治高尿酸血症及痛风的新方法提供参考。     

Diet Effects in Gut Microbiome and Obesity

The 100 trillion microbes in human gut coevolve with the host and exert significant influences on human health. The gut microbial composition presents dynamic changes correlated with various factors including host genotypes, age, and external environment. Effective manipulation of the gut microbiota through diets (both long‐term and short‐term diet patterns), probiotics and/or prebiotics, and antibiotics has been proved being potential to prevent from metabolic disorders such as obesity in many studies. The dietary regulation exerts influences on microbial metabolism and host immune functions through several pathways, of which may include selectively bacterial fermentation of nutrients, lower intestinal barrier function, overexpression of genes associated with disorders, and disruptions to both innate and adaptive immunity. Discoveries in the interrelationship between diet, intestinal microbiome, and body immune system provide us novel perceptions to the specific action mechanisms and will promote the development of therapeutic approaches for obesity.     

Fabrication of quercetin-loaded nanoparticles based on Hohenbuehelia serotina polysaccharides and their modulatory effects on intestinal function and gut microbiota in vivo

This research was aimed to construct the nanoparticles based on Hohenbuehelia serotina polysaccharides for encapsulation of quercetin (QC-HSP NPs), and investigate their effects on intestinal function and gut microbiota in mice. Results showed that in comparison with HSP and control, QC-HSP NPs significantly improved immune organ indexes, colon length, fecal moisture content and intestinal peristalsis capacity of mice. The productions of short-chain fatty acids (SCFAs) in colon were also increased after treatment with QC-HSP NPs, while the colonic fecal pH was decreased and defecation time was shortened. Through analysis of 16S rRNA sequencing, QC-HSP NPs could increase α and β diversities of gut microbiota, modulate their structure and composition, and increase the relative abundance of beneficial bacteria together with reducing the richness of harmful bacteria. In addition, QC-HSP NPs ameliorated the metabolic functions of gut microbiota by modulating metabolic pathways. This study suggested that QC-HSP NPs might be served as a prebiotic for protecting intestinal health.     

植物多酚与肠道微生物群的相互作用及其对代谢性疾病影响的研究进展

肠道微生物群参与由胰岛素抵抗、高血糖、血脂异常、中心性肥胖和高血压等组成的代谢综合征的发展,进一步导致代谢性疾病的发生。而植物多酚可以促进肠道微生物群中有益菌的生长,间接减少致病菌的数量。并且肠道微生物群能够将高分子质量的植物多酚代谢为更具生物活性的代谢物以提高其生物利用度。本文综述了植物多酚与肠道微生物群两者之间的相互作用及它们对代谢性疾病的影响,为植物多酚的利用提供参考。     

Contrasting effects of fresh and fermented kimchi consumption on gut microbiota composition and gene expression related to metabolic syndrome in obese Korean women

Accumulating evidence suggests relationship of compositional changes of gut microbiota with onset of metabolic disorders and obesity. Kimchi, a traditional Korean side dish, is known for its beneficial impact on metabolic parameters and anti‐obesity effects. The current study was designed to evaluate the association between gut microbiota and human genome after kimchi intervention in an effort to understand the molecular mechanism(s) underlying the antiobesity impact of kimchi. Twenty‐four obese women were randomly assigned to either fresh or fermented kimchi group for eight weeks of kimchi intervention. Pyrosequencing of fecal microbiota and microarray analyses of blood samples revealed that fresh and fermented kimchi interventions exerted differential effects on the obesity‐related clinical parameters. Correlations of these effects with changes in blood gene expression and gut microbial population were more evident in the fermented kimchi group than the fresh kimchi group.     

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。