The interplay between diet,gut microbes,and host epigenetics in health and disease

The mechanisms linking the function of microbes to host health are becoming better defined but are not yet fully understood. One recently explored mechanism involves microbe-mediated alterations in the host epigenome. Consumption of specific dietary components such as fiber, glucosinolates, polyphenols, and dietary fat has a significant impact on gut microbiota composition and function. Microbial metabolism of these dietary components regulates important epigenetic functions that ultimately influences host health. Diet-mediated alterations in the gut microbiome regulate the substrates available for epigenetic modifications like DNA methylation or histone methylation and/or acetylation. In addition, generation of microbial metabolites such as butyrate inhibits the activity of core epigenetic enzymes like histone deacetylases (HDACs). Reciprocally, the host epigenome also influences gut microbial composition. Thus, complex interactions exist between these three factors. This review comprehensively examines the interplay between diet, gut microbes, and host epigenetics in modulating host health. Specifically, the dietary impact on gut microbiota structure and function that in-turn regulates host epigenetics is evaluated in terms of promoting protection from disease development.     

肠道菌群及其代谢产物对心肌纤维化影响与治疗的研究进展

心肌纤维化是多种心血管疾病,如冠心病、心肌梗死和心力衰竭等的终末期表现和主要致病因素。研究发现,免疫和炎症过程在心肌纤维化的发病机制中起决定性作用。近年来,人们发现肠道微生物在心肌纤维化的发病机制和发展中起着至关重要的作用。肠道菌群的失调可导致微生物的代谢产物转移到血液循环中,如短链脂肪酸、脂多糖和氧化三甲胺等。这些代谢物直接或间接地诱导组织损伤免疫和激活全身炎症反应,进而影响心肌纤维化。如何改变肠道菌群来改善心肌纤维化已成为当前的研究重点,包括饮食干预、使用抗生素、补充益生菌和益生元,以及粪便微生物群移植等。本综述旨在回顾肠道菌群及其代谢产物与心肌纤维化的相互作用,介绍通过干预肠道菌群改善心肌纤维化的研究进展,为心肌纤维化的治疗提供新思路。     

基于代谢组学的植物多酚及其肠道健康效应研究进展

综述了植物多酚的分类和来源、在代谢组学技术的驱动下,新型多酚物质的鉴定、控制植物多酚合成途径的关键因子以及多酚的功能特性的研究进展,阐述了植物多酚在肠道中的代谢以及其作为“益生元”调节肠道微生态并影响机体健康的重要功能。目前的研究表明不同植物多酚在调节肠道微生态方面存在差异,多数有促进肠道有益菌作用,并通过与肠道微生物“互作”发挥促进健康效应。总之,植物多酚作为“益生元”影响人体健康可能离不开肠道微生物的介导。各个植物多酚的益生功能也需要进一步阐析,在此过程中需要考虑宿主,膳食等混杂因素的综合影响,且需要拓展临床应用方面的研究。     

肠道微生物调控宿主食欲的研究进展

肠道微生物与宿主代谢相互作用,可调节机体的生理功能。宿主机体中存在"微生物-肠道-大脑轴",肠道菌群可通过多种途径影响中枢神经系统,进而对宿主摄食等行为产生影响。食物中不易被宿主消化吸收的膳食纤维等营养物质,被肠道微生物发酵可产生多种代谢产物,这些代谢产物作为信号分子可通过不同途径介导中枢神经系统,进而调控宿主食欲。本文主要综述了肠道微生物及其代谢产物对中枢神经系统与宿主食欲的影响及其可能的调控途径与机制,以加深肠道微生物在调控宿主食欲方面的新认识。     

Dynamics of Gut Microbiota in Autoimmune Lupus

Gut microbiota has been recognized as an important environmental factor in health, as well as in metabolic and immunological diseases, in which perturbation of the host gut microbiota is often observed in the diseased state. However, little is known on the role of gut microbiota in systemic lupus erythematosus. We investigated the effects of host genetics, sex, age, and dietary intervention on the gut microbiome in a murine lupus model. In young, female lupus-prone mice resembling women at childbearing age, a population with the highest risk for lupus, we found marked depletion of lactobacilli, and increases in Lachnospiraceae and overall diversity compared to age-matched healthy controls. The predicted metagenomic profile in lupus-prone mice showed a significant enrichment of bacterial motility- and sporulation-related pathways. Retinoic acid as a dietary intervention restored lactobacilli that were downregulated in lupus-prone mice, and this correlated with improved symptoms. The predicted metagenomes also showed that retinoic acid reversed many lupus-associated changes in microbial functions that deviated from the control. In addition, gut microbiota of lupus-prone mice were different between sexes, and an overrepresentation of Lachnospiraceae in females was associated with an earlier onset of and/or more severe lupus symptoms. Clostridiaceae and Lachnospiraceae, both harboring butyrate-producing genera, were more abundant in the gut of lupus-prone mice at specific time points during lupus progression. Together, our results demonstrate the dynamics of gut microbiota in murine lupus and provide evidence to suggest the use of probiotic lactobacilli and retinoic acid as dietary supplements to relieve inflammatory flares in lupus patients.     

Host and gut microbiota symbiotic factors: lessons from inflammatory bowel disease and successful symbionts

Humans are colonized by a diverse collection of microbes, the largest numbers of which reside in the distal gut. The vast majority of humans coexist in a beneficial equilibrium with these microbes. However, disruption of this mutualistic relationship can manifest itself in human diseases such as inflammatory bowel disease. Thus the study of inflammatory bowel disease and its genetics can provide insight into host pathways that mediate host-microbiota symbiosis. Bacteria of the human intestinal ecosystem face numerous challenges imposed by human dietary intake, the mucosal immune system, competition from fellow members of the gut microbiota, transient ingested microbes and invading pathogens. Considering features of human resident gut bacteria provides the opportunity to understand how microbes have achieved their symbiont status. While model symbionts have provided perspective into host-microbial homeostasis, high-throughput approaches are becoming increasingly practical for functionally characterizing the gut microbiota as a community.     

The development of gut immune responses and gut microbiota: effects of probiotics in prevention and treatment of allergic disease

The infant's immature intestinal immune system develops as it comes into contact with dietary and microbial antigens in the gut. The evolving indigenous intestinal microbiota have a significant impact on the developing immune system and there is accumulating evidence indicating that an intimate interaction between gut microbiota and host defence mechanisms is mandatory for the development and maintenance of a balance between tolerance to innocuous antigens and capability of mounting an inflammatory response towards potential pathogens. Disturbances in the mucosal immune system are reflected in the composition of the gut microbiota and vice versa. Distinctive alterations in the composition of the gut microbiota appear to precede the manifestation of atopic disease, which suggests a role for the interaction between the intestinal immune system and specific strains of the microbiota in the pathogenesis of allergic disorders. The administration of probiotics, strains of bacteria from the healthy human gut microbiota, have been shown to stimulate antiinflammatory, tolerogenic immune responses, the lack of which has been implied in the development of atopic disorders. Thus probiotics may prove beneficial in the prevention and alleviation of allergic disease.     

Molecular Paths Linking Metabolic Diseases,Gut Microbiota Dysbiosis and Enterobacteria Infections

Alterations of both ecology and functions of gut microbiota are conspicuous traits of several inflammatory pathologies, notably metabolic diseases such as obesity and type 2 diabetes. Moreover, the proliferation of enterobacteria, subdominant members of the intestinal microbial ecosystem, has been shown to be favored by Western diet, the strongest inducer of both metabolic diseases and gut microbiota dysbiosis. The inner interdependence between the host and the gut microbiota is based on a plethora of molecular mechanisms by which host and intestinal microbes modify each other. Among these mechanisms are as follows: (i) the well-known metabolic impact of short chain fatty acids, produced by microbial fermentation of complex carbohydrates from plants; (ii) a mutual modulation of miRNAs expression, both on the eukaryotic (host) and prokaryotic (gut microbes) side; (iii) the production by enterobacteria of virulence factors such as the genotoxin colibactin, shown to alter the integrity of host genome and induce a senescence-like phenotype in vitro; (iv) the microbial excretion of outer-membrane vesicles, which, in addition to other functions, may act as a carrier for multiple molecules such as toxins to be delivered to target cells. In this review, I describe the major molecular mechanisms by which gut microbes exert their metabolic impact at a multi-organ level (the gut barrier being in the front line) and support the emerging triad of metabolic diseases, gut microbiota dysbiosis and enterobacteria infections.     

Amino acid supplements and metabolic health: a potential interplay between intestinal microbiota and systems control

Dietary supplementation of essential amino acids (EAAs) has been shown to promote healthspan. EAAs regulate, in fact, glucose and lipid metabolism and energy balance, increase mitochondrial biogenesis, and maintain immune homeostasis. Basic science and epidemiological results indicate that dietary macronutrient composition affects healthspan through multiple and integrated mechanisms, and their effects are closely related to the metabolic status to which they act. In particular, EAA supplementation can trigger different and even opposite effects depending on the catabolic and anabolic states of the organisms. Among others, gut-associated microbial communities (referred to as gut microbiota) emerged as a major regulator of the host metabolism. Diet and host health influence gut microbiota, and composition of gut microbiota, in turn, controls many aspects of host health, including nutrient metabolism, resistance to infection, and immune signals. Altered communication between the innate immune system and the gut microbiota might contribute to complex diseases. Furthermore, gut microbiota and its impact to host health change largely during different life phases such as lactation, weaning, and aging. Here we will review the accumulating body of knowledge on the impact of dietary EAA supplementation on the host metabolic health and healthspan from a holistic perspective. Moreover, we will focus on the current efforts to establish causal relationships among dietary EAAs, gut microbiota, and health during human development.     

Gut dysbacteriosis and intestinal disease: mechanism and treatment

The gut microbiome functions like an endocrine organ, generating bioactive metabolites, enzymes or small molecules that can impact host physiology. Gut dysbacteriosis is associated with many intestinal diseases including (but not limited to) inflammatory bowel disease, primary sclerosing cholangitis-IBD, irritable bowel syndrome, chronic constipation, osmotic diarrhoea and colorectal cancer. The potential pathogenic mechanism of gut dysbacteriosis associated with intestinal diseases includes the alteration of composition of gut microbiota as well as the gut microbiota–derived signalling molecules. The many correlations between the latter and the susceptibility for intestinal diseases has placed a spotlight on the gut microbiome as a potential novel target for therapeutics. Currently, faecal microbial transplantation, dietary interventions, use of probiotics, prebiotics and drugs are the major therapeutic tools utilized to impact dysbacteriosis and associated intestinal diseases. In this review, we systematically summarized the role of intestinal microbiome in the occurrence and development of intestinal diseases. The potential mechanism of the complex interplay between gut dysbacteriosis and intestinal diseases, and the treatment methods are also highlighted.     

Benefits of polyphenols on gut microbiota and implications in human health

The biological properties of dietary polyphenols are greatly dependent on their bioavailability that, in turn, is largely influenced by their degree of polymerization. The gut microbiota play a key role in modulating the production, bioavailability and, thus, the biological activities of phenolic metabolites, particularly after the intake of food containing high-molecular-weight polyphenols. In addition, evidence is emerging on the activity of dietary polyphenols on the modulation of the colonic microbial population composition or activity. However, although the great range of health-promoting activities of dietary polyphenols has been widely investigated, their effect on the modulation of the gut ecology and the two-way relationship “polyphenols ? microbiota” are still poorly understood.Only a few studies have examined the impact of dietary polyphenols on the human gut microbiota, and most were focused on single polyphenol molecules and selected bacterial populations. This review focuses on the reciprocal interactions between the gut microbiota and polyphenols, the mechanisms of action and the consequences of these interactions on human health.     

Modulation of the gut microbiota by nutrients with prebiotic properties: consequences for host health in the context of obesity and metabolic syndrome

The gut microbiota is increasingly considered as a symbiotic partner for the maintenance of health. The homeostasis of the gut microbiota is dependent on host characteristics (age, gender, genetic background...), environmental conditions (stress, drugs, gastrointestinal surgery, infectious and toxic agents...). Moreover, it is dependent on the day-to-day dietary changes. Experimental data in animals, but also observational studies in obese patients, suggest that the composition of the gut microbiota is a factor characterizing obese versus lean individuals, diabetic versus non diabetic patients, or patients presenting hepatic diseases such as non alcoholic steatohepatitis. Interestingly, the changes in the gut microbes can be reversed by dieting and related weight loss. The qualitative and quantitative changes in the intake of specific food components (fatty acids, carbohydrates, micronutrients, prebiotics, probiotics), have not only consequences on the gut microbiota composition, but may modulate the expression of genes in host tissues such as the liver, adipose tissue, intestine, muscle. This in turn may drive or lessen the development of fat mass and metabolic disturbances associated with the gut barrier function and the systemic immunity. The relevance of the prebiotic or probiotic approaches in the management of obesity in humans is supported by few intervention studies in humans up to now, but the experimental data obtained with those compounds help to elucidate novel potential molecular targets relating diet with gut microbes. The metagenomic and integrative metabolomic approaches could help elucidate which bacteria, among the trillions in human gut, or more specifically which activities/genes, could participate to the control of host energy metabolism, and could be relevant for future therapeutic developments.     

Putative Mechanisms Underlying the Beneficial Effects of Polyphenols in Murine Models of Metabolic Disorders in Relation to Gut Microbiota

The beneficial effects of polyphenols on metabolic disorders have been extensively reported. The interaction of these compounds with the gut microbiota has been the focus of recent studies. In this review, we explored the fundamental mechanisms underlying the beneficial effects of polyphenols in relation to the gut microbiota in murine models of metabolic disorders. We analyzed the effects of polyphenols on three murine models of metabolic disorders, namely, models of a high-fat diet (HFD)-induced metabolic disorder, dextran sulfate sodium (DSS)-induced colitis, and a metabolic disorder not associated with HFD or DSS. Regardless of the model, polyphenols ameliorated the effects of metabolic disorders by alleviating intestinal oxidative stress, improving inflammatory status, and improving intestinal barrier function, as well as by modulating gut microbiota, for example, by increasing the abundance of short-chain fatty acid-producing bacteria. Consequently, polyphenols reduce circulating lipopolysaccharide levels, thereby improving inflammatory status and alleviating oxidative imbalance at the lesion sites. In conclusion, polyphenols likely act by regulating intestinal functions, including the gut microbiota, and may be a safe and suitable therapeutic agent for various metabolic disorders.     

Circadian orchestration of host and gut microbiota in infection

Circadian rhythms are present in almost every organism and regulate multiple aspects of biological and physiological processes (e.g. metabolism, immune responses, and microbial exposure). There exists a bidirectional circadian interaction between the host and its gut microbiota, and potential circadian orchestration of both host and gut microbiota in response to invading pathogens. In this review, we summarize what is known about these intestinal microbial oscillations and the relationships between host circadian clocks and various infectious agents (bacteria, fungi, parasites, and viruses), and discuss how host circadian clocks prime the immune system to fight pathogen infections as well as the direct effects of circadian clocks on viral activity (e.g. SARS-CoV-2 entry and replication). Finally, we consider strategies employed to realign normal circadian rhythmicity for host health, such as chronotherapy, dietary intervention, good sleep hygiene, and gut microbiota-targeted therapy. We propose that targeting circadian rhythmicity may provide therapeutic opportunities for the treatment of infectious diseases.     

基于肠道微生态探讨黄连素在代谢性疾病中的抗炎作用

肠道菌群与能量代谢密切相关,其组成和代谢紊乱可通过多种途径导致胰岛素抵抗,肥胖和2型糖尿病。黄连素因具有减重、降糖、调脂等作用被广泛用于肥胖、2型糖尿病及非酒精性脂肪性肝病等代谢性疾病的辅助治疗;研究表明,黄连素可调节肠道菌群的组成和代谢,改善肠道微生态环境,从而改善胰岛素抵抗和代谢。本文综述了黄连素通过肠道菌群-炎症轴在干预代谢性疾病的研究进展,以期为代谢性疾病的治疗寻找新的策略,并为今后该领域的深入研究提供指导意义。     

肠黏膜屏障与肠道菌群的相互关系

摘要：人类肠道中微生物群与肠道环境相互作用以维持机体健康。肠黏膜屏障主要由黏液层、肠道菌群、肠道免疫系统和肠上皮细胞本身的完整性等构成。肠道作为直接与大量菌群接触的器官,其屏障功能在肠道健康中的作用尤为显著。肠道菌群与肠道屏障相互作用,保持肠道菌群与肠道屏障相对稳定,肠道菌群参与肠道免疫反应的建立,共同建立机体天然防御系统,在保持肠道免疫的动态平衡中具有重要作用。当两者之间的平衡被打破时,可诱发功能性胃肠病（如肠易激综合征）及免疫相关性疾病（如炎症性肠病）。本文主要阐述肠黏膜屏障与肠道菌群之间的相互关系以及与肠道屏障功能障碍相关的肠道疾病。     

肠道菌群-肠-脑-肌轴信号交流的研究进展

肠道菌群及其代谢产物在老年神经退行性疾病、胃肠道疾病以及肌肉骨骼系统性疾病的发病与康复中的作用越来越受到关注。肠道菌群及其代谢产物可通过免疫、内分泌和神经系统等多种途径调节大脑神经或肌肉骨骼系统功能;反之,肠道、大脑或肌肉骨骼系统也可通过炎症、代谢或线粒体通路作用于肠道系统,调节肠道菌群微生态,形成肠道菌群与肠-脑、肠-肌、 肠-脑-肌之间的双向信号交流机制,从而影响机体健康。因此,本综述总结了肠道菌群如何通过代谢产物、肠道通透性和免疫-神经通路建立起肠-脑-肌之间的相互联系,为促进大脑神经的可塑性和改善肌肉健康提供新思路。