营养支持对肠道菌群与肠黏膜免疫的影响

肠内营养(EN)有助于保持肠黏膜的屏障功能,维护肠黏膜的结构完整性,促进肠黏膜固有免疫和获得性免疫的产生,维持肠道菌群的平衡和多样性。肠外营养(PN)能预防胃肠道功能障碍患者进一步营养不良的发生,挽救危重症患者的生命,然而PN会增加危重症患者感染并发症的发生。全肠外营养(TPN)时肠黏膜免疫受损,肠道菌群(GM)紊乱,滋养性喂养能显著改善肠黏膜的免疫功能,促进肠道内稳态的恢复。GM紊乱加重肠黏膜的炎症反应,或将进一步加重肠黏膜免疫的损害。因此,全面理解营养支持、GM与肠黏膜免疫之间的相互关系具有重要意义。     

肠道菌群功能研究进展

人体中寄居着大量的微生物,即共生菌群,这些菌群的基因总和称为微生物组。存在于人体中的各种菌群和微生物组对人体的健康和疾病发挥着重要作用。正常情况下肠道菌群与人体处于共生关系,具有防御外源性感染、促进免疫系统的成熟与平衡、营养与代谢等生理功能。肠道共生菌群的紊乱则与许多疾病有关,包括过敏性疾病、自身免疫性疾病、代谢性疾病、细菌感染和结肠癌等。     

The Immunopathogenesis of Alzheimer’s Disease Is Related to the Composition of Gut Microbiota

The microbiota–gut–brain axis plays an important role in the development of neurodegenerative diseases. Commensal and pathogenic enteric bacteria can influence brain and immune system function by the production of lipopolysaccharides and amyloid. Dysbiosis of the intestinal microbiome induces local and consecutively systemic immune-mediated inflammation. Proinflammatory cytokines then trigger neuroinflammation and finally neurodegeneration. Immune-mediated oxidative stress can lead to a deficiency of vitamins and essential micronutrients. Furthermore, the wrong composition of gut microbiota might impair the intake and metabolization of nutrients. In patients with Alzheimer’s disease (AD) significant alterations of the gut microbiota have been demonstrated. Standard Western diet, infections, decreased physical activity and chronic stress impact the composition and diversity of gut microbiota. A higher abundancy of “pro-inflammatory” gut microbiota goes along with enhanced systemic inflammation and neuroinflammatory processes. Thus, AD beginning in the gut is closely related to the imbalance of gut microbiota. Modulation of gut microbiota by Mediterranean diet, probiotics and curcumin can slow down cognitive decline and alter the gut microbiome significantly. A multi-domain intervention approach addressing underlying causes of AD (inflammation, infections, metabolic alterations like insulin resistance and nutrient deficiency, stress) appears very promising to reduce or even reverse cognitive decline by exerting positive effects on the gut microbiota.     

Immune Impairment Associated with Vitamin A Deficiency: Insights from Clinical Studies and Animal Model Research

Vitamin A (VA) is critical for many biological processes, including embryonic development, hormone production and function, the maintenance and modulation of immunity, and the homeostasis of epithelium and mucosa. Specifically, VA affects cell integrity, cytokine production, innate immune cell activation, antigen presentation, and lymphocyte trafficking to mucosal surfaces. VA also has been reported to influence the gut microbiota composition and diversity. Consequently, VA deficiency (VAD) results in the imbalanced production of inflammatory and immunomodulatory cytokines, intestinal inflammation, weakened mucosal barrier functions, reduced reactive oxygen species (ROS) and disruption of the gut microbiome. Although VAD is primarily known to cause xerophthalmia, its role in the impairment of anti-infectious defense mechanisms is less defined. Infectious diseases lead to temporary anorexia and lower dietary intake; furthermore, they adversely affect VA status by interfering with VA absorption, utilization and excretion. Thus, there is a tri-directional relationship between VAD, immune response and infections, as VAD affects immune response and predisposes the host to infection, and infection decreases the intestinal absorption of the VA, thereby contributing to secondary VAD development. This has been demonstrated using nutritional and clinical studies, radiotracer studies and knockout animal models. An in-depth understanding of the relationship between VAD, immune response, gut microbiota and infections is critical for optimizing vaccine efficacy and the development of effective immunization programs for countries with high prevalence of VAD. Therefore, in this review, we have comprehensively summarized the existing knowledge regarding VAD impacts on immune responses to infections and post vaccination. We have detailed pathological conditions associated with clinical and subclinical VAD, gut microbiome adaptation to VAD and VAD effects on the immune responses to infection and vaccines.     

Impact of the intestinal environment on the immune responses to vaccination

Vaccination has contributed greatly to the control of infectious diseases; however, regional and individual differences are occasionally observed in the efficacy of vaccination. As one explanation for these differences, much attention has focused on the intestinal environment constructed by the interaction of diet and the gut microbiota. The intestinal environment has several physiological effects on the host immune system, both locally and systemically, and consequently influences the efficacy of vaccination. In this review, we discuss the impact of the gut microbiota and dietary nutrients on systemic and oral vaccination as well as their applications in various strategies for immunoregulation, including use as vaccine adjuvants. This information could contribute to establishing methods of personalized vaccination that would optimize host immunity by changing the gut environment to maximize vaccine effects.     

Synthetic Microbiomes on the Rise—Application in Deciphering the Role of Microbes in Host Health and Disease

The intestinal microbiota conveys significant benefits to host physiology. Although multiple chronic disorders have been associated with alterations in the intestinal microbiota composition and function, it is still unclear whether these changes are a cause or a consequence. Hence, to translate microbiome research into clinical application, it is necessary to provide a proof of causality of host–microbiota interactions. This is hampered by the complexity of the gut microbiome and many confounding factors. The application of gnotobiotic animal models associated with synthetic communities allows us to address the cause–effect relationship between the host and intestinal microbiota by reducing the microbiome complexity on a manageable level. In recent years, diverse bacterial communities were assembled to analyze the role of microorganisms in infectious, inflammatory, and metabolic diseases. In this review, we outline their application and features. Furthermore, we discuss the differences between human-derived and model-specific communities. Lastly, we highlight the necessity of generating novel synthetic communities to unravel the microbial role associated with specific health outcomes and disease phenotypes. This understanding is essential for the development of novel non-invasive targeted therapeutic strategies to control and modulate intestinal microbiota in health and disease.     

Impact of Dietary Flavanols on Microbiota,Immunity and Inflammation in Metabolic Diseases

Flavanols are natural occurring polyphenols abundant in fruits and vegetables to which have been attributed to beneficial effects on health, and also against metabolic diseases, such as diabetes, obesity and metabolic syndrome. These positive properties have been associated to the modulation of different molecular pathways, and importantly, to the regulation of immunological reactions (pro-inflammatory cytokines, chemokines, adhesion molecules, nuclear factor-κB [NF-κB], inducible enzymes), and the activity of cells of the immune system. In addition, flavanols can modulate the composition and function of gut microbiome in a prebiotic-like manner, resulting in the positive regulation of metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. Moreover, the biotransformation of flavanols by gut bacteria increases their bioavailability generating a number of metabolites with potential to affect human metabolism, including during metabolic diseases. However, the exact mechanisms by which flavanols act on the microbiota and immune system to influence health and disease remain unclear, especially in humans where these connections have been scarcely explored. This review seeks to summarize recent advances on the complex interaction of flavanols with gut microbiota, immunity and inflammation focus on metabolic diseases.     

肠道菌群在结核分枝杆菌感染及其治疗中的相关性研究进展

结核病是由结核分枝杆菌(Mycobacterium tuberculosis,Mtb)感染而引起的慢性传染性疾病。Mtb感染人类后,其感染状态与宿主自身的免疫、代谢、遗传学机制等密切相关。肠道菌群及其代谢物通过参与宿主免疫反应和新陈代谢在结核病的病理生理过程及其治疗中其起重要作用。本文将从“肺-肠轴”、肠道菌群代谢产物在Mtb感染中的作用、结核化疗对肠道菌群的影响及肠道菌群在结核治疗中的潜在作用进行综述。     

Gut Microbiota and Probiotics/Synbiotics for Modulation of Immunity in Critically Ill Patients

Patients suffering from critical illness have host inflammatory responses against injuries, such as infection and trauma, that can lead to tissue damage, organ failure, and death. Modulation of host immune response as well as infection and damage control are detrimental factors in the management of systemic inflammation. The gut is the motor of multiple organ failure following injury, and it is recognized that gut dysfunction is one of the causative factors of disease progression. The gut microbiota has a role in maintaining host immunity, and disruption of the gut microbiota might induce an immunosuppressive condition in critically ill patients. Treatment with probiotics and synbiotics has been reported to attenuate systemic inflammation by maintaining gut microbiota and to reduce postoperative infectious complications and ventilator-associated pneumonia. The administration of prophylactic probiotics/synbiotics could be an important treatment option for preventing infectious complications and modulating immunity. Further basic and clinical research is needed to promote intestinal therapies for critically ill patients.     

肠道微生态研究技术在代谢综合征中的应用

哺乳动物肠道内定居着数量庞大且组分复杂的微生物群,它们共同构成了肠道微生物组。近年来,人们逐渐认识到肠道微生物与一些疾病的发生和发展密切相关,如代谢性疾病、炎症性肠病、肿瘤、免疫系统以及神经系统疾病等,使得肠道微生物成为研究的热点。迅猛发展的微生物研究技术为我们提供了高效有力的技术平台,推动了对肠道微生态的系统认知,也为疾病的诊断及治疗开辟了新思路。本文旨在总结与分析目前常用微生态研究技术的最新进展及其局限性,为进一步的肠道微生物组研究提供参考,并简要介绍肠道微生态与代谢综合征的相关研究成果。     

Exploring the Potential of Human Milk and Formula Milk on Infants’ Gut and Health

Early-life gut microbiota plays a role in determining the health and risk of developing diseases in later life. Various perinatal factors have been shown to contribute to the development and establishment of infant gut microbiota. One of the important factors influencing the infant gut microbial colonization and composition is the mode of infant feeding. While infant formula milk has been designed to resemble human milk as much as possible, the gut microbiome of infants who receive formula milk differs from that of infants who are fed human milk. A diverse microbial population in human milk and the microbes seed the infant gut microbiome. Human milk contains nutritional components that promote infant growth and bioactive components, such as human milk oligosaccharides, lactoferrin, and immunoglobulins, which contribute to immunological development. In an attempt to encourage the formation of a healthy gut microbiome comparable to that of a breastfed infant, manufacturers often supplement infant formula with prebiotics or probiotics, which are known to have a bifidogenic effect and can modulate the immune system. This review aims to elucidate the roles of human milk and formula milk on infants’ gut and health.     

益生菌在肠内营养中的应用及研究进展

防治肠源性感染的关键在于防止肠内细菌和(或)内毒素的移位,纠正肠内菌群平衡的紊乱和失调,改善肠黏膜屏障功能以及提高肠道局部的免疫功能。而益生菌是具有维持肠内菌群平衡、防止肠黏膜屏障的破坏、增强局部免疫功能、促进和改善消化道蠕动以及吸收等作用的非致病性微生物,可治疗和预防肠源性感染。以下综述益生菌在肠内营养的作用及研究进展。     

HDHL-INTIMIC: A European Knowledge Platform on Food,Diet, Intestinal Microbiomics,and Human Health

Studies indicate that the intestinal microbiota influences general metabolic processes in humans, thereby modulating the risk of chronic diseases such as type 2 diabetes, allergy, cardiovascular disease, and colorectal cancer (CRC). Dietary factors are also directly related to chronic disease risk, and they affect the composition and function of the gut microbiota. Still, detailed knowledge on the relation between diet, the microbiota, and chronic disease risk is limited. The overarching aim of the HDHL-INTIMIC (INtesTInal MICrobiomics) knowledge platform is to foster studies on the microbiota, nutrition, and health by assembling available knowledge of the microbiota and of the other aspects (e.g., food science and metabolomics) that are relevant in the context of microbiome research. The goal is to make this information findable, accessible, interoperable, and reusable (FAIR) to the scientific community, and to share information with the various stakeholders. Through these efforts a network of transnational and multidisciplinary collaboration has emerged, which has contributed to further develop and increase the impact of microbiome research in human health. The roles of microbiota in early infancy, during ageing, and in subclinical and clinically manifested disease are identified as urgent areas of research in this knowledge platform.     

Prebiotics, immune function, infection and inflammation: a review of the evidence

Beta2-1 fructans are carbohydrate molecules with prebiotic properties. Through resistance to digestion in the upper gastrointestinal tract, they reach the colon intact, where they selectively stimulate the growth and/or activity of beneficial members of the gut microbiota. Through this modification of the intestinal microbiota, and by additional mechanisms, beta2-1 fructans may have beneficial effects upon immune function, ability to combat infection, and inflammatory processes and conditions. In this paper, we have collated, summarised and evaluated studies investigating these areas. Twenty-one studies in laboratory animals suggest that some aspects of innate and adaptive immunity of the gut and the systemic immune systems are modified by beta2-1 fructans. In man, two studies in children and nine studies in adults indicate that the adaptive immune system may be modified by beta2-1 fructans. Thirteen studies in animal models of intestinal infections conclude a beneficial effect of beta2-1 fructans. Ten trials involving infants and children have mostly reported benefits on infectious outcomes; in fifteen adult trials, little effect was generally seen, although in specific situations, certain beta2-1 fructans may be beneficial. Ten studies in animal models show benefit of beta2-1 fructans with regard to intestinal inflammation. Human studies report some benefits regarding inflammatory bowel disease (four positive studies) and atopic dermatitis (one positive study), but findings in irritable bowel syndrome are inconsistent. Therefore, overall the results indicate that beta2-1 fructans are able to modulate some aspects of immune function, to improve the host's ability to respond successfully to certain intestinal infections, and to modify some inflammatory conditions.     

Partial Enteral Nutrition Preserves Elements of Gut Barrier Function,Including Innate Immunity,Intestinal Alkaline Phosphatase (IAP) Level,and Intestinal Microbiota in Mice

Lack of enteral nutrition (EN) during parenteral nutrition (PN) leads to higher incidence of infection because of gut barrier dysfunction. However, the effects of partial EN on intestina linnate immunity, intestinal alkaline phosphatase (IAP) and microbiota remain unclear. The mice were randomized into six groups to receive either standard chow or isocaloric and isonitrogenous nutritional support with variable partial EN to PN ratios. Five days later, the mice were sacrificed and tissue samples were collected. Bacterial translocation, the levels of lysozyme, mucin 2 (MUC2), and IAP were analyzed. The composition of intestinal microbiota was analyzed by 16S rRNA pyrosequencing. Compared with chow, total parenteral nutrition (TPN) resulted in a dysfunctional mucosal barrier, as evidenced by increased bacterial translocation (p < 0.05), loss of lysozyme, MUC2, and IAP, and changes in the gut microbiota (p < 0.001). Administration of 20% EN supplemented with PN significantly increased the concentrations of lysozyme, MUC2, IAP, and the mRNA levels of lysozyme and MUC2 (p < 0.001). The percentages of Bacteroidetes and Tenericutes were significantly lower in the 20% EN group than in the TPN group (p < 0.001). These changes were accompanied by maintained barrier function in bacterial culture (p < 0.05). Supplementation of PN with 20% EN preserves gut barrier function, by way of maintaining innate immunity, IAP and intestinal microbiota.     

The role of probiotics in gastrointestinal surgery

The intestinal microbiota, which is a complex and dynamic population of different bacterial species, represents an important contribution to the health of the host. This microbiota plays a key role by promoting the integrity of the epithelial barrier and the development of mucosal immunity. However, under some stressful situations, such as after gastrointestinal surgery, infectious complications may originate from the intestinal microbiota of the patient. This phenomenon is known as the gut origin of sepsis hypothesis. However, the supply of probiotics has beneficial effects under similar conditions despite some controversial results. Therefore, it is important to carefully assess the efficacy of probiotics in the prevention and treatment of complications in surgical patients and to evaluate the safety of its use. This review provides an overview of the proposed mechanisms of probiotic action and the significant progress in this field, mainly concerning gastrointestinal surgery.     

The Crosstalk between the Gut Microbiota Composition and the Clinical Course of Allergic Rhinitis: The Use of Probiotics,Prebiotics and Bacterial Lysates in the Treatment of Allergic Rhinitis

Although massive progress in discovering allergic rhinitis (AR) aetiology has been made in recent years, its prevalence is still rising and it significantly impacts patients’ lives. That is why further and non-conventional research elucidating the role of new factors in AR pathogenesis is needed, facilitating discoveries of new treatment approaches. One of these factors is the gut microbiota, with its specific roles in health and disease. This review presents the process of gut microbiota development, especially in early life, focusing on its impact on the immune system. It emphasizes the link between the gut microbiota composition and immune changes involved in AR development. Specifically, it elucidates the significant link between bacteria colonizing the gut and the Th1/Th2 imbalance. Probiotics, prebiotics and bacterial lysates, which are medications that restore the composition of intestinal bacteria and indirectly affect the clinical course of AR, are also discussed.     

Impaired Mucosal Homeostasis in Short-Term Fiber Deprivation Is Due to Reduced Mucus Production Rather Than Overgrowth of Mucus-Degrading Bacteria

The gut mucosal environment is key in host health; protecting against pathogens and providing a niche for beneficial bacteria, thereby facilitating a mutualistic balance between host and microbiome. Lack of dietary fiber results in erosion of the mucosal layer, suggested to be a result of increased mucus-degrading gut bacteria. This study aimed to use quantitative analyses to investigate the diet-induced imbalance of mucosal homeostasis. Seven days of fiber-deficiency affected intestinal anatomy and physiology, seen by reduced intestinal length and loss of the colonic crypt-structure. Moreover, the mucus layer was diminished, muc2 expression decreased, and impaired mucus secretion was detected by stable isotope probing. Quantitative microbiome profiling of the gut microbiota showed a diet-induced reduction in bacterial load and decreased diversity across the intestinal tract, including taxa with fiber-degrading and butyrate-producing capabilities. Most importantly, there was little change in the absolute abundance of known mucus-degrading bacteria, although, due to the general loss of taxa, relative abundance would erroneously indicate an increase in mucus degraders. These findings underscore the importance of using quantitative methods in microbiome research, suggesting erosion of the mucus layer during fiber deprivation is due to diminished mucus production rather than overgrowth of mucus degraders.     

Probiotics and mucosal barrier in children

PURPOSE OF REVIEW: Colonization by the microbiota plays an important role in intestinal tract maturation of newborn. Once installed, indigenous microbiota maintains this modulation and also protects against infectious aggression. Due to these abilities, gut microbiota can be considered a 'microbial organ' that contributes to health of human host. Factors can affect microbiota colonization as well as its maintenance and ingestion of probiotics is a promissory way to counteract these perturbations. This review discusses recent papers dealing with the use of probiotics and their effects on intestinal barrier in children. RECENT FINDINGS: Data obtained from experiments in animal models or cell cultures as well as from clinical trials suggest that probiotics may prevent infectious and inflammatory diseases in which reduction of mucosal barrier functions is involved. SUMMARY: Recent results suggest that probiotics control maturation and maintenance of the intestinal barrier in children. However, human data are limited and more biological and well controlled clinical trials must be carried out for a more precise understanding of the mechanisms underlying the probiotic action and the balance of the complex gastrointestinal ecosystem with which probiotics are expected to interact.