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.     

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.     

肠-肝轴介导的非酒精性脂肪性肝病及其营养干预研究进展

非酒精性脂肪性肝病（non-alcoholic fatty liver disease,NAFLD）是全球最常见的肝脏疾病。NAFLD始于肝脏脂质堆积,继而可能引起炎症,最终导致肝纤维化。有研究表明,肠道微生物及其产生的多种生物活性物质,通过门静脉与宿主肝细胞相互作用,进而导致NAFLD的发生发展,这种肠道和肝脏之间的双向通信,称为肠-肝轴。本文从肠道微生物组成、肠道屏障功能、肠道微生物成分、肠道微生物代谢物的角度阐述肠-肝轴介导NAFLD发生发展的作用机制,以及以肠-肝轴为靶点通过营养干预改善NAFLD;综述了肠道紊乱和NAFLD之间错综复杂相互作用的现有机制,以期为预防和改善NAFLD提供一定的营养策略。     

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.     

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.     

Inflammatory Diseases and Vitamin E—What Do We Know and Where Do We Go?

Inflammation‐driven diseases and related comorbidities, such as the metabolic syndrome, obesity, fatty liver disease, and cardiovascular diseases cause significant global burden. There is a growing body of evidence that nutrients alter inflammatory responses and can therefore make a decisive contribution to the treatment of these diseases. Recently, the inflammasome, a cytosolic multiprotein complex, has been identified as a key player in inflammation and the development of various inflammation‐mediated disorders, with nucleotide‐binding domain and leucine‐rich repeat pyrin domain (NLRP) 3 being the inflammasome of interest. Here an overview about the cellular signaling pathways underlying nuclear factor “kappa‐light‐chain‐enhancer” of activated B‐cells (NF‐κB)‐ and NLRP3‐mediated inflammatory processes, and the pathogenesis of the inflammatory diseases atherosclerosis and non‐alcoholic fatty liver disease (NAFLD) is provided; next, the current state of knowledge for drug‐based and dietary‐based interventions for treating cardiovascular diseases and NAFLD is discussed. To date, one of the most important antioxidants in the human diet is vitamin E. Various in vitro and in vivo studies suggest that the different forms of vitamin E and also their derivatives have anti‐inflammatory activity. Recent publications suggest that vitamin E—and possibly metabolites of vitamin E—are a promising therapeutic approach for treating inflammatory diseases such as NAFLD.     

Mitochondria‐Mediated Pathogenesis and Therapeutics for Non‐Alcoholic Fatty Liver Disease

Non‐alcoholic fatty liver disease (NAFLD) has become a worldwide epidemic over the last decade. Remarkable progress has been made in understanding the pathogenesis of NAFLD and, subsequently, in developing medications to treat this disease. Although the mechanisms of NAFLD are complex and multifactorial, accumulating and emerging evidence indicates that mitochondria play a critical role in the pathogenesis and progression of NAFLD. Pharmacologic therapies acting on mitochondria may therefore pave the way to novel strategies for the prevention and protection against NAFLD. This review focuses on new insights into the role of hepatic mitochondrial dysfunction in NAFLD, and summarizes recent studies on mitochondria‐centric therapies for NAFLD utilizing new medications or repurposing of currently available drugs. Although some studies presented may feature controversial results or are still in lack of clinical verification, it is undoubted that medications that may spare the mitochondria from multiple levels of damage are highly promising, and have begun to be used with some degree of success.     

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 fat and gut microbiota: mechanisms involved in obesity control

ABSTRACT

Obesity is a serious global health problem that is directly related to various morbidities manifestation. Intestinal dysbiosis has been implicated on obesity pathogenesis. Diet composition can alter gut microbiota, regardless of energy intake. Dietary fatty acids quality may affect gut microbiota composition, which in turn may affect host metabolic health. The mechanisms by which the different type of FFA modulate gut microbiota is yet poor elucidate and there is a lack of studies regard to this. Fatty acids may act in cell membrane, interfere with energy production, inhibit enzymatic activities, impair nutrient absorption and generate toxic compounds to cells, leading to growth inhibition or even bacterial death. The beneficial effect of the consumption of n-3 polyunsaturated fatty acids (PUFA) and conjugated linoleic acid (CLA) on microbiota, unlike n-6 PUFA and saturated fatty acids has been suggested. n-3 PUFA consumption promotes desirable changes on obese intestinal microbiota making it similar to that of normal weight individuals. More studies are needed to better understand the effect of CLA on microbiota and host health. Long term human controlled clinical trials must be conducted to allow us to understand the complex interaction between dietary fat, intestinal microbiota and obesity.     

膳食纤维通过调节肠道微生物及其代谢产物对动脉粥样硬化的影响研究进展

膳食纤维是一种不可被消化和吸收的碳水化合物聚合物,能够通过调节肠道微生物群的生长,促进肠道微生物区系的动态平衡,进而影响肠道微生物代谢产物如脂多糖、三甲胺N-氧化物、短链脂肪酸和胆汁酸的产生,达到调节宿主生理健康的目的.动脉粥样硬化是一种慢性炎症性疾病,其发生发展与脂质代谢紊乱和炎症反应关系密切.而肠道微生物及其代谢产...     

Research progress regarding the effect and mechanism of dietary phenolic acids for improving nonalcoholic fatty liver disease via gut microbiota

Phenolic acids (PAs), a class of small bioactive molecules widely distributed in food and mainly found as secondary plant metabolites, present significant advantages such as antioxidant activity and other health benefits. The global epidemic of nonalcoholic fatty liver disease (NAFLD) is becoming a serious public health problem. Existing studies showed that gut microbiota (GM) dysbiosis is highly associated with the occurrence and development of NAFLD. In recent years, progress has been made in the study of the relationship among PA compounds, GM, and NAFLD. PAs can regulate the composition and functions of the GM to promote human health, while GM can increase the dietary sources of PAs and improve its bioavailability. This paper discussed PAs, GM, and their interrelationship while introducing several representative dietary PA sources and examining the absorption and metabolism of PAs mediated by GM. It also summarizes the effect and mechanisms of PAs in improving and regulating NAFLD via GM and their metabolites. This helps to better evaluate the potential preventive effect of PAs on NAFLD via the regulation of GM and expands the utilization of PAs and PA-rich food resources.     

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.     

Dietary polysaccharide from Mung bean [Vigna radiate (Linn.) Wilczek] skin modulates gut microbiota and short-chain fatty acids in mice

Cumulative evidence revealed that the gut microbiota play important role in human health. Polysaccharide from Mung bean [Vigna radiate (Linn.) Wilczek] skin has been confirmed to have a variety of biological activities, but its effect on the gut microbiota has not been considered. This study aimed to investigate the effect of hot water extraction of mung bean skin water-soluble polysaccharides (MBP-2) on the gut microbiota of Balb/c mice and its main metabolite short-chain fatty acids (SCFAs). The results showed that supplementation with MBP-2 increased the colon length and the production of SCFAs in Balb/c mice, and improved the intestinal microenvironment by producing SCFAs, which is beneficial to the intestinal health of mice. MBP-2 increased the Chao1 index and ACE index in a dose-depended manner, and changed the structure of the gut microbiota and significantly promoted the growth of probiotic bacteria in Balb/c mice. The faecal bacterial flora of mice is mainly composed of nine phyla and twenty-seven genera, MBP-2 can regulate the composition of intestinal flora by increasing Firmicutes, Bacteroidetes, Clostridium and decreasing TM7, thereby maintaining intestinal health.     

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。     

n-3多不饱和脂肪酸、内质网应激与非酒精性脂肪肝病的研究进展

非酒精性脂肪性肝病(nonalcoholic fatty liver disease, NAFLD)已逐渐成为一个全球性健康问题, 但其发病的具体机制不甚明朗。内质网是细胞内蛋白质加工、脂质合成和钙储存的主要场所, 内质网结构和功能的失常所致的内质网应激(endoplasmic reticulum stress, ERS)对脂代谢和细胞功能具有重要调控作用, 可能是NAFLD的发生和发展的重要机制。近来大量研究显示, 脂类中特定的脂质负荷(饱和脂肪酸、胆固醇)可能是诱导ERS导致NAFLD重要原因, 而另一方面, n-3多不饱和脂肪酸(n-3 polyunsaturated fatty acids, n-3 PUFA)的摄入量却与NAFLD患病率呈负相关。本文就脂肪酸与内质网应激及其与NAFLD的联系作一综述, 进一步探讨n-3多不饱和脂肪酸防治NAFLD的机制。     

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.     

Infant formula supplemented with 1,3-olein-2-palmitin regulated the immunity,gut microbiota,and metabolites of mice colonized by feces from healthy infants

Infant formula is currently an important food to cope with insufficient breastfeeding. Although 1,3-olein-2-palmitin (OPO) has been used in infant formula, its effects on the immune system, gut microbiota, and metabolites for infants remain unclear. This study constructed a mouse model of colonizing healthy infant feces using antibiotic treatment and fecal microbial transplantation. Thus, the gap between the infant formula supplemented with OPO and human milk in mouse serum biochemistry, immune system, intestinal microbiota, short-chain fatty acid production, and metabolites was evaluated. Our results showed that regarding IL-9, IL-10 levels, fecal secretory IgA, and endotoxin, formula supplemented with OPO and human milk types had comparable levels. Additionally, OPO slightly increased the content of short-chain fatty acids. The 16S rRNA gene sequence analysis and metabonomics analysis demonstrated that feeding different foods affects the gut microbiota of mice; in particular, supplementing formula feeding with OPO enriched the abundance of bifidobacteria. Furthermore, feeding different foods leads to unique intestinal content of metabolites, and the gut microbiota regulates the metabolites' differences. Our results reveal a brand new perspective of OPO regarding gut microbiota and metabolites.     

Intake of Bifidobacterium lactis Probio-M8 fermented milk protects against alcoholic liver disease

Alcoholic liver disease (ALD) is a liver disease caused by long-term heavy drinking, which is characterized by increased inflammation and oxidative stress in the liver and gut dysbiosis. The purpose of this study was to investigate the protective effect of administering ordinary and probiotic- (containing the Bifidobacterium animalis ssp. lactis Probio-M8 strain; M8) fermented milk to rats. Several biochemical parameters and the fecal metagenomes were monitored before (d 0) and after (d 42) the intervention. Our results confirmed that alcohol could cause significant changes in the liver levels of the proinflammatory cytokine IL-1β, antioxidation indicators, and liver function-related indicators; meanwhile, the gut bacterial and viral microbiota were disrupted with significant reduction in microbial diversity and richness. Feeding the rats with Probio-M8-fermented milk effectively maintained the gut microbiota stability, reduced liver inflammation and oxidative stress, and mitigated liver damages in ALD. Moreover, the Probio-M8-fermented milk reversed alcohol-induced dysbiosis by restoring the gut microbiota diversity, richness, and composition. Four predicted fecal metabolites (inositol, tryptophan, cortisol, and vitamin K2) increased after the intervention, which might help regulate liver metabolism and alleviate ALD-related symptoms. In short, our data supported that consuming Probio-M8-fermented milk effectively mitigated ALD. The protective effect against ALD could be related to changes in the gut microbiome after probiotic-fermented milk consumption. However, such observation and the causal relationship among probiotic milk consumption, changes in gut microbiome, and disease alleviation would still need to be further confirmed. Nevertheless, this study has shown in a rat model that consuming probiotic-fermented milk could protect against ALD.