肠道微生物群落与炎症性肠病关系研究进展

目的炎症性肠病（IBD）包括克罗恩病（CD）和溃疡性结肠炎（UC）,以持续性肠道非特异性炎症为特征,通常反复发作、迁延不愈,临床上仍无特效性的治疗手段。IBD确切的发病机制尚不清楚,涉及免疫、环境及遗传等因素,这些因素共同诱导肠道炎症、黏膜损伤和修复。肠道微生物群落及其代谢产物、宿主基因易感性及肠道黏膜免疫三方面共同参与了IBD的发病机制。本文从消化道微生态角度出发,对目前IBD相关的肠道微生物群落研究现状、宿主-微生物间免疫应答及益生菌治疗等内容进行探讨。     

The role of intestinal microbiota in cardiovascular disease

Accumulating evidence has indicated that intestinal microbiota is involved in the development of various human diseases, including cardiovascular diseases (CVDs). In the recent years, both human and animal experiments have revealed that alterations in the composition and function of intestinal flora, recognized as gut microflora dysbiosis, can accelerate the progression of CVDs. Moreover, intestinal flora metabolizes the diet ingested by the host into a series of metabolites, including trimethylamine N‐oxide, short chain fatty acids, secondary bile acid and indoxyl sulfate, which affects the host physiological processes by activation of numerous signalling pathways. The aim of this review was to summarize the role of gut microbiota in the pathogenesis of CVDs, including coronary artery disease, hypertension and heart failure, which may provide valuable insights into potential therapeutic strategies for CVD that involve interfering with the composition, function and metabolites of the intestinal flora.     

The impact of the intestinal microbiota in therapeutic responses against cancer

Accumulating evidence points to the impact of the gut microbiota in regulating various chronic inflammatory disorders such as cancers. The intestinal microbiome is not only influencing the spontaneous course of colon malignancies but also acts at distant sterile sites of neoplasia, mostly playing a detrimental role. By providing microbial-associated molecular patterns and potentially antigens sharing molecular mimicry with tumor antigens, our commensals modulate the local and the systemic immune tonus, eventually influencing tumor microenvironment. Complicating this algorithm, therapeutic interventions alter the delicate balance between the epithelium, the microbial community, and the intestinal immunity, governing the final clinical outcome. This seminar focused on the impact of the intestinal composition on the immunomodulatory and therapeutic activities of distinct compounds (alkylating agents, platinum salts and immunotherapies) used in oncology. This research opens up “the era of anticancer probiotics” aimed at restoring gut eubiosis for a better clinical outcome in cancer patients.     

肠道微生物在重症急性胰腺炎进展中的作用及其潜在的治疗意义

重症急性胰腺炎是临床常见的消化系统急危重症,起病急、变化快、并发症多、病死率高,但尚无特效疗法,是目前医学界面临的一大难题.近年来,肠道微生物因其在人类健康和疾病中的重要作用而受到越来越多的关注.研究表明,重症急性胰腺炎早期即存在肠道微生物失调,而由胰腺炎引起的菌群失调和菌群移位导致的肠源性感染是影响重症急性胰腺炎严重...     

The role of biogeography in shaping diversity of the intestinal microbiota in house mice

The microbial communities inhabiting the mammalian intestinal tract play an important role in diverse aspects of host biology. However, little is known regarding the forces shaping variation in these communities and their influence on host fitness. To shed light on the contributions of host genetics, transmission and geography to diversity in microbial communities between individuals, we performed a survey of intestinal microbial communities in a panel of 121 house mice derived from eight locations across Western Europe using pyrosequencing of the bacterial 16S rRNA gene. The host factors studied included population structure estimated by microsatellite loci and mitochondrial DNA, genetic distance and geography. To determine whether host tissue (mucosa)‐associated communities display properties distinct from those of the lumen, both the caecal mucosa and contents were examined. We identified Bacteroides, Robinsoniella and Helicobacter as the most abundant genera in both the caecal content and mucosa‐associated communities of wild house mice. Overall, we found geography to be the most significant factor explaining patterns of diversity in the intestinal microbiota, with a comparatively weaker influence of host population structure and genetic distance. Furthermore, the influence of host genetic distance was limited to the mucosa communities, consistent with this environment being more intimately coupled to the host.     

Endogenous retroviruses promote homeostatic and inflammatory responses to the microbiota

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急性心肌梗死患者肠道优势菌群分析

目的探讨急性心肌梗死患者肠道优势菌群的改变及其与疾病严重程度的关系。方法共筛选急性心肌梗死患者71名及正常健康体检者33名,急性心肌梗死患者根据是否心衰分为急性心肌梗死组36名和急性心肌梗死伴泵衰竭组35名,所有入选者收集大便及血清标本,分别采用qPCR及化学发光仪测定肠道优势菌群改变和血清脑钠肽前体及肌钙蛋白水平。结果急性心肌梗死患者肠道优势菌群显著改变,肠道肠杆菌以及肠球菌细菌数量较对照组显著增加,均与脑钠肽前体、肌钙蛋白、Killip分级显著正相关,而双歧杆菌、乳酸杆菌等细菌数量显著降低,与脑钠肽前体、肌钙蛋白、Killip分级显著负相关。结论急性心肌梗死患者呈现典型的肠道菌群紊乱,且与患者疾病严重程度相关。     

肠道微生物群在介导肠道病原体定植抗性作用的研究进展

肠道微生物群是复杂的微生态系统的组成部分, 参与机体一系列重要的生理过程。健康微生物群在稳态条件下的一个关键功能是抵抗外界病原体的定植, 称为定植抗性。抗生素和质子泵抑制剂的使用, 可引起菌群组成的改变和定植抗性的减弱, 从而为病原体在肠道定植提供了机会, 最终导致感染。细菌性肠道感染是全球疾病的主要原因。肠道微生物群提供定植抗性的机制尚未完全阐明, 但主要分为直接机制和间接机制, 包括抗菌产物的分泌、营养竞争、肠道屏障完整性和免疫反应。本文将从以上几个方面探讨肠道微生物群介导的对肠道病原体的定植抗性。

     

肠道菌群在炎症性肠病发病中的作用

炎症性肠病(IBD)是一种非特异性肠道炎症性疾病,其病因和发病机制尚不完全明确。肠道菌群作为一个非常复杂的微生态系统,在IBD的患病机制中扮演着非常重要的角色。本研究就肠道微生态系统、肠道菌群与IBD发病的关系以及肠道菌群调控对IBD的作用的最新进展进行综述。     

The intestinal microbiota plays a role in Salmonella-induced colitis independent of pathogen colonization

The intestinal microbiota is composed of hundreds of species of bacteria, fungi and protozoa and is critical for numerous biological processes, such as nutrient acquisition, vitamin production, and colonization resistance against bacterial pathogens. We studied the role of the intestinal microbiota on host resistance to Salmonella enterica serovar Typhimurium-induced colitis. Using multiple antibiotic treatments in 129S1/SvImJ mice, we showed that disruption of the intestinal microbiota alters host susceptibility to infection. Although all antibiotic treatments caused similar increases in pathogen colonization, the development of enterocolitis was seen only when streptomycin or vancomycin was used; no significant pathology was observed with the use of metronidazole. Interestingly, metronidazole-treated and infected C57BL/6 mice developed severe pathology. We hypothesized that the intestinal microbiota confers resistance to infectious colitis without affecting the ability of S. Typhimurium to colonize the intestine. Indeed, different antibiotic treatments caused distinct shifts in the intestinal microbiota prior to infection. Through fluorescence in situ hybridization, terminal restriction fragment length polymorphism, and real-time PCR, we showed that there is a strong correlation between the intestinal microbiota composition before infection and susceptibility to Salmonella-induced colitis. Members of the Bacteroidetes phylum were present at significantly higher levels in mice resistant to colitis. Further analysis revealed that Porphyromonadaceae levels were also increased in these mice. Conversely, there was a positive correlation between the abundance of Lactobacillus sp. and predisposition to colitis. Our data suggests that different members of the microbiota might be associated with S. Typhimurium colonization and colitis. Dissecting the mechanisms involved in resistance to infection and inflammation will be critical for the development of therapeutic and preventative measures against enteric pathogens.     

The role of intestinal microbiota and its metabolites in intestinal and extraintestinal organ injury induced by intestinal ischemia reperfusion injury

Intestinal ischemia/reperfusion (I/R) is a common pathophysiological process in clinical severe patients, and the effect of intestinal I/R injury on the patient''s systemic pathophysiological state is far greater than that of primary intestinal injury. In recent years, more and more evidence has shown that intestinal microbiota and its metabolites play an important role in the occurrence, development, diagnosis and treatment of intestinal I/R injury. Intestinal microbiota is regulated by host genes, immune response, diet, drugs and other factors. The metabolism and immune potential of intestinal microbiota determine its important significance in host health and diseases. Therefore, targeting the intestinal microbiota and its metabolites may be an effective therapy for the treatment of intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury. This review focuses on the role of intestinal microbiota and its metabolites in intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury, and summarizes the latest progress in regulating intestinal microbiota to treat intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury.     

Stem cells of intestinal epithelium. The mechanisms of survival and the role of microbiota

The thanatogenetic mechanisms of stem cells (sc) of rapidly renewing system of intestinal epithelium still remain unclear. on the one hand they are definitely involved into basic mechanisms of carcinogenesis in the gastrointestinal tract, because dysregulation of programs responsible for elimination of “unwanted” mutant cells (which are normally under immune and own intrinsic control) is one of the reasons of neoplastic expansion. on the other hand elucidation and characterization of the regulatory machinery controlling sc survival are interrelated with problems of clinical medicine, including the increase of therapeutic efficiency of treatment of inflammatory and ulcer lesions of the gut, traumatic and surgical wounds, as well as restriction of side effects in normal tissues induced by application of intensive methods chemo- and radiotherapy of cancer. the latter is especially important for treatment of blood diseases and tumors of peritoneal cavity organs mainly due to bone marrow and intestinal epithelium damage. (These tissues are the most sensitive to these treatments.) The review considers data on exogenous and genetic modifiers of sc survival, and also the basic principles of mechanisms involved into renewal and regeneration of sc and the effects of microbiota on these processes.     

消化道微生物区系与肥胖关系的研究进展

肥胖以及与肥胖相关的一些疾病威胁着发达国家和发展中国家,这些疾病包括Ⅱ型糖尿病、高血压、心血管疾病、非酒精型脂肪肝。最新研究表明消化道微生物区系(microbiota,指一个特定区域中所有活的微生物群落的统称。)可能与宿主肥胖相关。目前此类研究尚处于起步阶段,作者总结了以往研究结果,对消化道微生物区系的组成和作用、与宿主能量代谢相关的消化道微生物种类和作用、消化道微生物区系影响宿主能量储存的途径作了较为详细的介绍。并探讨了目前研究中存在的问题,总结了本实验室已有研究成果,以及今后可能的研究方向。     

The tripeptide feG ameliorates systemic inflammatory responses to rat intestinal anaphylaxis

Background  

Food allergies are generally associated with gastrointestinal upset, but in many patients systemic reactions occur. However, the systemic effects of food allergies are poorly understood in experimental animals, which also offer the opportunity to explore the actions of anti-allergic drugs. The tripeptide D-phenylalanine-D-glutamate-Glycine (feG), which potentially alleviates the symptoms of systemic anaphylactic reactions, was tested to determine if it also reduced systemic inflammatory responses provoked by a gastric allergic reaction.     

肠道菌群在肿瘤发生发展及免疫治疗中作用的研究进展北大核心CSCD

肠道菌群是一个与人体共生的复杂微生物区系,近年来被越来越多的研究者所关注。研究发现,肠道菌群不仅在维持人体正常生理功能中起到重要作用,在肿瘤发生、发展、诊断及治疗中也有不可忽视的作用。本文在对肠道菌群与肿瘤关系进行概述的基础上,重点介绍了肠道菌群促进肿瘤发生、发展的主要机制,以及肠道菌群对抗肿瘤免疫治疗尤其是免疫检查点抑制疗法的影响。此外,文中还总结了目前可行的调节肠道菌群以提高肿瘤治疗疗效的方法,并提出了其中可能存在的困难和挑战。     

石斛多糖通过改善肠道屏障功能、调节肠道微生物群、减少氧化应激和炎症反应改善右旋糖酐-硫酸钠诱导的小鼠结肠炎

结肠炎是一种慢性疾病,主要症状表现为腹痛、腹泻和体重减轻。结肠炎的病因很可能是环境因素和遗传易感性共同作用,导致肠上皮屏障瓦解和对肠道菌群的免疫反应失调。在结肠炎条件下,紧密连接蛋白的下调表达会导致肠道对微生物配体和有害代谢物的通透性增加,最终引发全身炎症。治疗结肠炎的传统方法是通过免疫抑制剂、免疫调节剂和生物制剂抑制炎症反应。然而,长期使用它们可能会导致严重的副作用,例如增加对继发感染和癌症的易感性。     

The midgut microbiota plays an essential role in sand fly vector competence for Leishmania major

For many arthropod vectors, the diverse bacteria and fungi that inhabit the gut can negatively impact pathogen colonization. Our attempts to exploit antibiotic treatment of colonized Phlebotomus duboscqi sand flies in order to improve their vector competency for Leishmania major resulted instead in flies that were refractory to the development of transmissible infections due to the inability of the parasite to survive and to colonize the anterior midgut with infective, metacyclic stage promastigotes. The parasite survival and development defect could be overcome by feeding the flies on different symbiont bacteria but not by feeding them on bacterial supernatants or replete medium. The inhibitory effect of the dysbiosis was moderated by lowering the concentration of sucrose (<30% w/v) used in the sugar feeds to maintain the colony. Exposure of promastigotes to 30% sucrose was lethal to the parasite in vitro. Confocal imaging revealed that the killing in vivo was confined to promastigotes that had migrated to the anterior plug region, corresponding to the highest concentrations of sucrose. The data suggest that sucrose utilization by the microbiota is essential to promote the appropriate osmotic conditions required for the survival of infective stage promastigotes in vivo.