Has the microbiota played a critical role in the evolution of the adaptive immune system?

Although microbes have been classically viewed as pathogens, it is now well established that the majority of host-bacterial interactions are symbiotic. During development and into adulthood, gut bacteria shape the tissues, cells, and molecular profile of our gastrointestinal immune system. This partnership, forged over many millennia of coevolution, is based on a molecular exchange involving bacterial signals that are recognized by host receptors to mediate beneficial outcomes for both microbes and humans. We explore how specific aspects of the adaptive immune system are influenced by intestinal commensal bacteria. Understanding the molecular mechanisms that mediate symbiosis between commensal bacteria and humans may redefine how we view the evolution of adaptive immunity and consequently how we approach the treatment of numerous immunologic disorders.     

Immunology. Therapeutic manipulation of gut flora

In developed countries as many as two individuals in every thousand suffer from inflammatory bowel disease (ulcerative colitis and Crohn's disease). In his Perspective, Shanahan discusses a new therapeutic approach to treating these conditions in which bacteria normally found in the gut are engineered to produce the anti-inflammatory cytokine interleukin-10 and then are fed as probiotics to mice with these disorders (Steidler et al.).     

耐硼赖氨酸芽孢杆菌的保护剂筛选及其对罗非鱼肠道微生物群落的影响

本研究目的是为了探究耐硼赖氨酸芽孢杆菌（Lysinibacillus boronitolerans,YS11）的保存条件及其对罗非鱼肠道微生物多样性和丰度的影响,为微生物饲料添加剂的研发提供科学依据。选择海藻糖、乳糖、蔗糖和脱脂奶粉4种保护剂,并通过浓度梯度优化筛选最佳保护剂,结果表明,YS11在10%海藻糖中,干燥后保持较高的存活率。罗非鱼幼苗饲喂菌体发酵液,喂养70 d后,通过高通量测序观察YS11对罗非鱼肠道微生物群落的影响,结果表明,添加YS11的处理改变了罗非鱼肠道微生物群及其多样性,提高罗非鱼肠道中有益菌的丰度,降低某些潜在致病菌的丰度。本研究结果证实,10%海藻糖为最佳冷冻干燥保护剂;耐硼赖氨酸芽孢杆菌能够调节肠道微生物群,促进益生菌生长,抑制病原菌生长。     

特异性敲除肠道miR-146a对小鼠肠道菌群的影响

【目的】miR-146a作为抑炎因子,仍然不清楚其是否参与宿主与微生物间的互作,进而影响肠道稳态,因此本文旨在研究miR-146a对小鼠肠道菌群的影响。【方法】以肠道miR-146a特异性敲除小鼠(CKO鼠)及对照小鼠(Flox鼠)为研究对象,利用16S rRNA高通量测序法检测2组空肠段的微生物菌群分布。【结果】测序共获得1 134个用于物种分类的OTUs,包括37门、80纲、161目、198科、261属、117种的细菌;Flox组和CKO组小鼠的空肠微生物中共有46个相同的OTUs;各组肠道微生物中厚壁菌门Firmicutes、拟杆菌门Bacteroidota、疣微菌门Verrucomicrobiota、变形菌门Proteobacteria和脱硫杆菌门Desulfobacterota是优势菌门;2组肠道微生物群落组成整体相似,但CKO组梭状芽孢杆菌纲Clostridia的平均相对丰度高于Flox组(P=0.067),毛螺菌目Lachnospirales平均相对丰度显著高于Flox组(P<0.05),其他层级组成无显著差异。【结论】miR-146a敲除可改变宿主肠道梭状芽孢杆菌...     

Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria

The mammalian intestinal tract is colonized by trillions of beneficial commensal bacteria that are anatomically restricted to specific niches. However, the mechanisms that regulate anatomical containment remain unclear. Here, we show that interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) are present in intestinal tissues of healthy mammals. Depletion of ILCs resulted in peripheral dissemination of commensal bacteria and systemic inflammation, which was prevented by administration of IL-22. Disseminating bacteria were identified as Alcaligenes species originating from host lymphoid tissues. Alcaligenes was sufficient to promote systemic inflammation after ILC depletion in mice, and Alcaligenes-specific systemic immune responses were associated with Crohn's disease and progressive hepatitis C virus infection in patients. Collectively, these data indicate that ILCs regulate selective containment of lymphoid-resident bacteria to prevent systemic inflammation associated with chronic diseases.     

益生菌在治疗炎症性肠病方面的应用

从炎症性肠疾病（IBDs）的发病原因入手,重点阐述了益生菌在调节肠道菌群平衡、维护肠粘膜屏膜功能以及调节肠相关免疫体系平衡缓解和治疗炎症性肠疾病方面的作用机理。     

基于高通量测序的有机种植蔬菜地土壤微生物多样性分析

【目的】从微生物角度探究有机种植方式的优越性,揭示影响微生物群落多样性的环境因子,为建立合理的种植制度提供理论依据。【方法】以有机种植与常规种植方式的0~15和15~30 cm土壤为研究对象,采用高通量测序技术分析土壤微生物群落结构的差异,基于db RDA分析明确影响微生物群落结构的关键土壤环境因子。【结果】2种种植方式下土壤微生物的丰富度指数和多样性指数均以细菌高于真菌。有机种植表层0~15 cm土壤细菌和真菌群落的多样性、丰富度和物种的均匀度均较高,且与其他土层有显著差异(P<0.05,下同)。2种种植方式均表现为细菌以变形菌门、真菌以子囊菌门为优势菌门。有机种植方式显著提高细菌群落中放线菌门和绿弯菌门、真菌群落中担子菌门和球囊菌门的相对丰度,其中15~30 cm土层中放线菌门的相对丰度显著高于0~15 cm,而真菌2个菌门的相对丰度在不同土层间未表现出明显差别;常规种植则明显增加细菌中变形菌门和酸杆菌门及真菌中被胞菌门、壶菌门和捕虫霉门的相对丰度。有机种植能增加土壤中Haliangium和Mortierella等有益微生物类群的数量,常规种植则显著提升土传病害致病菌Ralstonia及植物病原菌Fusarium、Colletotrichum的数量和丰度。dbRDA分析表明,土壤环境因子对细菌群落的影响依次为全氮>全磷>有机质>pH>全钾,土壤环境因子对真菌群落的影响依次为全氮>全磷>pH>有机质>全钾。pH、有机质、全氮和全磷是显著影响土壤微生物群落结构的关键因子。【结论】不同土层起核心作用的微生物群落存在明显差异;有机种植能增加土壤中有益微生物菌群的丰度,降低土传病害及致病微生物的丰度。土壤全氮、全磷、有机质和p H是影响微生物群落结构的主要驱动因子。     

The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine

The mammalian intestine is home to ~100 trillion bacteria that perform important metabolic functions for their hosts. The proximity of vast numbers of bacteria to host intestinal tissues raises the question of how symbiotic host-bacterial relationships are maintained without eliciting potentially harmful immune responses. Here, we show that RegIIIγ, a secreted antibacterial lectin, is essential for maintaining a ~50-micrometer zone that physically separates the microbiota from the small intestinal epithelial surface. Loss of host-bacterial segregation in RegIIIγ(-/-) mice was coupled to increased bacterial colonization of the intestinal epithelial surface and enhanced activation of intestinal adaptive immune responses by the microbiota. Together, our findings reveal that RegIIIγ is a fundamental immune mechanism that promotes host-bacterial mutualism by regulating the spatial relationships between microbiota and host.     

Multiple effects of grape seed polyphenolics to prevent metabolic diseases

Obesity is increasing in developing countries. Population studies show a relationship between affluence and obesity. Changing food intake patterns with affluence such as preference for foods with less astringent polyphenolic compounds and dietary fibers may increase risk of metabolic dysfunctions due to caloric imbalance. Animal models of obesity consistently show that grape seed procyanidins prevent increases in body and abdo- minal adipose weight gain, plasma cholesterol, liver weight gain and inflammation in animals on high fat diets. The mechanisms are not clear because the oral intake of procyanidins results in pleiotropic interactions with proteins in the mouth, stomach, small intestine, cecum and colon that affect the rate of digestion of bioavailability of macronutrients, sterols, and dietary fiber. Procyanidins also bind bile acids and reduce intestinal permeability to inflammatory bacterial cell wall fragment. Procyanidins are not degraded or metabolized until reaching the lower gut where they can be metabolized into phenolic acids by gut bacteria. While they are metabolized by gut bacteria, they also alter total numbers and distribution of phyla and species of gut bacteria. Gut bacteria are recognized as significant contributors to obesity and obesity related metabolic diseases. The review examines the different pleiotropic effects of grape seed procyanidins that have a significant effect on metabolic disease in animal models of obesity.     

薄壳山核桃-小麦套作系统土壤微生物群落研究

为研究薄壳山核桃-小麦套作系统产量效益及土壤微生物群落情况,以薄壳山核桃单作(P)和薄壳山核桃-小麦套作(PW)为研究对象,分析比较2种模式下的产量效益,利用Illumina Miseq高通量测序技术对土壤细菌及真菌多样性、群落结构、标志物种和共现网络进行研究,并探究土壤化学性质与微生物的关系。结果表明：1)套作后坚果产量显著低于单作,总产值显著高于单作;2)套作导致土壤细菌多样性和真菌丰富度显著降低;3)细菌和真菌群落结构因套作显著改变,放线菌门(Actinobacteria)与担子菌门(Basidiomycota)丰度显著提高,酸杆菌门(Acidobacteria)丰度显著降低,微球菌科(Micrococcaceae)、黄色杆菌科(Xanthobacteraceae)、小单孢菌科(Micromonosporaceae)、鞘脂单胞菌属(Sphingomonas)、热酸菌属(Acidothermus)、芽单胞菌属(Gemmatimonas)、假节杆菌属(Pseudarthrobacter)和外瓶霉属(Exophiala)等标志物种于套作土壤中富集;4)套作使细菌网络复杂性增强,真菌网络...     

黑土细菌及真菌群落对长期施肥响应的差异及其驱动因素

【目的】研究长期施肥对黑土细菌和真菌群落结构影响差异,探索黑土肥力对长期施用化肥和有机肥响应差异的生物学机制,为黑土的肥力培育和合理施肥提供科学理论依据。【方法】基于35年的长期定位施肥试验,采用定量PCR方法和Miseq高通量测序技术,分析长期不施肥（CK）、氮肥（N）、有机肥（M）和有机无机配施肥（MN）处理下,黑土细菌及真菌的数量、群落结构和多样性的差异。同时结合土壤理化性状,探究不同施肥条件下细菌和真菌群落变化的环境驱动因子。【结果】N处理对土壤细菌的数量没有显著影响,但使其群落多样性降低了13.2%-48.5%。N处理使真菌的数量增加了24倍,多样性降低了4.6%-80.3%。与N处理相比,MN处理使细菌数量和多样性分别增加了2倍和7.7%-46.6%,而真菌的数量虽降低了14.2%,但其多样性提高了62%-237%。单施氮肥增加了土壤细菌酸杆菌门（Acidobacteria）中的Acidobacteria_Gp1、Gp3及变形菌门（Proteobacteria）中的α-Proteobacteria的相对丰度,并使土壤真菌中伞菌纲（Agaricomycetes）的相对丰度增加了41倍。与N处理相比,MN处理下细菌的各主要类群丰度未发生显著变化,但M处理下土壤细菌中的α-Proteobacteria、Acidobacteria_Gp1和Gp3丰度分别显著降低了26、97和81个百分点,Acidobacteria_Gp4、Gp6和Plancomycetes的丰度分别显著增加了11倍、9倍和2倍。细菌群落结构在MN与N处理之间无显著差异,明显区别于CK和M处理,pH为主要驱动因素,其阈值为6.07;真菌群落结构在CK、M和MN处理下相似,显著区别于N处理,两组处理之间差异由速效钾含量（125.5 mg·kg^-1）驱动。另外,有机质含量对于细菌和真菌群落均是重要的驱动因素,但调控细菌群落结构的阈值为28.4 g·kg^-1,而驱动真菌群落结构的阈值为30.8 g·kg^-1。【结论】黑土细菌对有机肥的响应较强,而真菌对化肥更为敏感。长期施用化肥会刺激土壤中嗜酸细菌和真菌的生长,而有机无机肥配施可提高土壤微生物群落多样性,刺激有益菌的生长。土壤pH和有效钾含量分别是调控细菌和真菌群落结构的重要影响因素,在黑土肥力培育中应引起充分的重视。     

重庆地区玉米叶内生细菌的分离及其与草地贪夜蛾肠道菌的比较

为进一步了解重庆地区玉米叶内生细菌的组成以及这些内生细菌与入侵重庆地区草地贪夜蛾肠道微生态的相互关系,以采集自巫山地区被草地贪夜蛾入侵的玉米地里的玉米嫩叶为材料,运用传统微生物培养方法尝试对其内生细菌进行初步的分离培养,并通过16S rDNA测序开展了优势菌的属水平鉴定.此次共分离获得了22个细菌分离株,经16S rDNA序列同源性分析,将它们归类到11个分类单元,分属克雷伯氏菌属(Klebsiella)、不动杆菌属(Acinetobacter)、寡养单胞菌属(Stenotrophomonas)、芽孢杆菌属(Bacillus)、肠球菌属(Enterococcus)、微杆菌属(Microbacterium)、鞘氨醇杆菌属(Sphingobacterium)、金黄杆菌属(Chryseobacterium)、无色杆菌属(Achromobacter)和丛毛单胞菌属(Comamonas).与前期研究得到的该地区草地贪夜蛾肠道微生物菌群数据比较可以发现,玉米内生细菌中包括克雷伯氏菌属(Klebsiella)、不动杆菌属(Acinetobacter)、肠球菌属(Enterococcus)、鞘氨醇杆菌属(Sphingobacterium)和金黄杆菌属(Chryseobacterium)在内的5个属可以在草地贪夜蛾肠道中分离到,表明草地贪夜蛾肠道微生物多数可能源自其食物,但是草地贪夜蛾肠道微生物中常见的假单胞菌属(Pseudomonas)、肠杆菌属(Enterobacter)、类芽孢杆菌属(Paenibacillus)、短波单胞菌属(Brevundimonas)和气单胞菌属(Aeromonas)并未在玉米嫩叶中分离到,说明它们可能是主要存在于草地贪夜蛾肠道中的微生物.该研究对草地贪夜蛾所取食的玉米叶中内生细菌的种类进行了初步分析,为后续研究玉米叶内生细菌和草地贪夜蛾肠道微生物的相互关系奠定了基础.     

不同种植模式对青稞根际土壤微生物群落结构的影响

采用Illumina MiSeq高通量测序技术,对6种种植模式下青稞根际土壤的16S rDNA和18S rDNA基因相关区片段进行测序,研究根际土壤细、真菌群落结构的变化,并结合土壤理化性质,分析环境因子与群落结构的关系,从根际土壤微生物生态系统的角度解析青稞连作障碍的发生机制。6种种植模式中,土壤有机质和全氮含量WHD模式最高,全磷含量YC模式最高,全钾含量MLS模式最高,pH均为碱性;3种连作模式下,随着连作年限的增长,土壤有机质、全氮和全钾逐年降低,全磷显著升高。6种种植模式下,细菌和真菌群落Alpha多样性指数和覆盖度没有显著差异,与连作相比,WHD和MLS模式可显著提高细菌群落的Shannon指数、ACE指数和Chao1指数;与混作、轮作相比,连作显著提高真菌群落的Shannon指数和ACE指数,但Chao1指数差异不显著;连作使细菌群落Alpha多样性减小,真菌群落Alpha多样性增加。6种种植模式下,genus水平群落结构表现为连作使青稞根际土壤中微生物区系发生较大改变,导致有害菌群丰度增加,有益菌群数量减少,尤其是真菌菌群发生较大改变,而轮、混作模式使优势菌群及新种数量明显增加。细菌、真菌群落PCoA分析结果表明,微生物群落在6种种植模式间变异较小且未发生明显分化,PC1、PC2的总解释能力均大于80%,表明有显著主导因子。细菌、真菌群落与土壤理化性质关系显示,土壤有机质、全氮与提高WDH、QKA模式下的细菌群落多样性呈正相关,而pH、有机质、全氮与提高WDH、YC、QKB模式下的真菌群落多样性呈正相关。表明,与连作相比,WDH和MLS模式可改善土壤理化性质,提高根际细菌群落结构多样性及微生物群落组成,是缓解青稞连作障碍的可能途径,可为青稞连作障碍修复措施的制定提供科学依据。     

不同连作年限菊花根际土壤微生物多样性变化特征

为揭示连作菊花根际土壤微生物群落结构和多样性变化特征,以不同连作年限菊花根际土壤为试验材料,采用高通量测序技术(Illumina-MiSeq)和生物信息学方法,分析无连作(CK)、连作2年(2a)、连作9年(9a)菊花根际土壤细菌和真菌的丰富度、多样性指数和群落结构,以期为菊花连作障碍防控提供理论支撑。结果表明,2a、9a根际土壤细菌数量和多样性较CK显著(P<0.05)增加,2a和9a的群落结构相似,共有OTU(operational taxonomic unit)比例高。连作对菊花根际土壤真菌群落多样性和丰度影响较小,但对真菌群落组成影响显著,2a、9a根际土壤真菌接合菌门、担子菌门和被孢霉属等群落丰度减少,明梭孢属、镰刀菌属、土赤壳菌等群落丰度增加。菊花连作会显著增加其根际土壤细菌数量和多样性,显著影响真菌群落结构组成。     

A genomic view of the human-Bacteroides thetaiotaomicron symbiosis

The human gut is colonized with a vast community of indigenous microorganisms that help shape our biology. Here, we present the complete genome sequence of the Gram-negative anaerobe Bacteroides thetaiotaomicron, a dominant member of our normal distal intestinal microbiota. Its 4779-member proteome includes an elaborate apparatus for acquiring and hydrolyzing otherwise indigestible dietary polysaccharides and an associated environment-sensing system consisting of a large repertoire of extracytoplasmic function sigma factors and one- and two-component signal transduction systems. These and other expanded paralogous groups shed light on the molecular mechanisms underlying symbiotic host-bacterial relationships in our intestine.     

卵孢长根菇不同生长期覆土层微生物群落结构多样性分析

【目的】探究卵孢长根菇不同生长期覆土层微生物群落结构多样性及木霉病害对微生物群落的影响,为长根菇的高产稳产提供理论依据。【方法】采用Illumina高通量测序技术,研究长根菇不同生长阶段(覆土时、现蕾期、采收期、发病期、转潮期)覆土层微生物群落结构组成及其多样性,并利用冗余分析技术分析研究微生物菌群与土壤理化因子的相关性。【结果】从覆土样品中共获得操作分类单元(OTUs)4581个,细菌和真菌OTUs分别为3650个和931个。不同生长阶段土壤的细菌优势菌群存在较大差异,覆土时和采收期的最优势属为广义伯克霍尔德氏菌属(Burkholderia),现蕾期、发病期、转潮期的最优势属的分别为罗尔斯通氏菌属(Ralstonia)、西地西菌属(Cedecea)和噬几丁质菌属(Chitinophaga)。覆工至采收的前3个生长期的最优势真菌属为镰刀菌属(Fusarium),其余生长期则为木霉属(Trichoderma)。木霉病害发病期土壤层微生物菌群结构发生较大变化,微生物数量和丰度均低于其他期;采收期土壤的细菌多样性最高,转潮期真菌多样性最高。冗余分析结果表明,覆土层中速效氮和速效钾与细菌在属水平上有显著正相关(P<0.05,下同);有效磷与真菌属水平菌群显著正相关。土壤有机质与覆土时土壤微生物群落呈正相关;速效氮、有效磷、速效钾和pH则与转潮期土壤微生物群落呈正相关。【结论】不同生长阶段覆土层土壤真菌物种数量在采收期达最大值,细菌物种数量则随着长根菇的生长而不断下降。木霉病害的发生对土壤微生物种类和丰度均有显著抑制作用,同时大量消耗土壤的营养元素,降低pH。     

Compartmentalized control of skin immunity by resident commensals

Intestinal commensal bacteria induce protective and regulatory responses that maintain host-microbial mutualism. However, the contribution of tissue-resident commensals to immunity and inflammation at other barrier sites has not been addressed. We found that in mice, the skin microbiota have an autonomous role in controlling the local inflammatory milieu and tuning resident T lymphocyte function. Protective immunity to a cutaneous pathogen was found to be critically dependent on the skin microbiota but not the gut microbiota. Furthermore, skin commensals tuned the function of local T cells in a manner dependent on signaling downstream of the interleukin-1 receptor. These findings underscore the importance of the microbiota as a distinctive feature of tissue compartmentalization, and provide insight into mechanisms of immune system regulation by resident commensal niches in health and disease.     

高通量测序法分析感杨树灰斑病前后叶围微生物多样性

采用高通量测序法,探究小黑杨(Populus simonii×P.nigra)灰斑病(Coryneum populinum Bres.)病叶与健康叶之间共生细菌和真菌群落结构的差异。结果表明:小黑杨叶片感病前后细菌与真菌的OTU变化巨大,2组样品共有的细菌种类有27个,仅占细菌总数的5.49%,共有真菌种类有22个,仅占真菌总数的0.71%。2组样品中菌落结构基本相同,但相对丰度差异较大,在门水平下,变形菌门(Proteobacteria)是优势细菌,子囊菌门(Ascomycota)是优势真菌。在属水平下,鞘氨醇单胞菌属(Sphingomonas)是健康叶中的优势细菌,假单胞菌属(Pseudomonas)是病叶中的优势细菌;枝孢属(Cladosporium)是健康叶中的优势真菌,镰刀菌属(Fusarium)是病叶中的优势真菌,其次是棒盘孢属(Coryneum)。     

浙江凤阳山不同海拔常绿阔叶林土壤微生物特征

【目的】探明浙江凤阳山地带性植被常绿阔叶林土壤微生物群落特征,明确土壤微生物群落沿海拔梯度的变化规律及影响微生物群落结构和多样性的主要因子。【方法】采集海拔343、765、1 364、1 611 m处土壤样品,利用高通量测序技术,探究土壤微生物群落与海拔的关系。【结果】凤阳山细菌操作分类单元(OTU)数量多于真菌,中低海拔(343和765 m)共有的OTU数目较多;Chao 1指数随海拔上升呈下降趋势,Shannon指数没有明显的变化规律。在门水平上,细菌群落优势类群为酸杆菌门Acidobacteria (43.77%～51.55%)、变形菌门Proteobacteria (31.18%～35.77%)和放线菌门Actinobacteria (5.24%～7.99%);真菌群落优势类群为担子菌门Basidiomycota (33.16%～67.35%)和子囊菌门Ascomycota(22.98%～46.78%)。相对丰度前10位的细菌门中,芽单胞菌门Gemmatimonadetes、硝化螺旋菌门Nitrospirae、疣微菌门Verrucomicrobia与海拔呈极显著负相关(P<...     

动物肠道放线菌的研究展望

动物肠道作为一个典型的、独特的环境,其肠道微生物的优势菌群是放线菌。过去将动物粪便为对象开展肠道放线菌资源研究的极少。本文对动物肠道放线菌的研究价值、菌种的多样性及其生物活性物质做了简要概述,其中肠道放线菌中具有抗肿瘤活性的菌株较多,所产生的生物活性物质还具有抗菌性,且酶活性比例较高。因此,动物肠道放线菌是开发药物和其他产品的重要来源,是一种新的微生物资源,具有巨大的开发潜力。