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1.
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.  相似文献   

2.
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.  相似文献   

3.
Intestinal bacteria aid host health and limit bacterial pathogen colonization. However, the influence of bacteria on enteric viruses is largely unknown. We depleted the intestinal microbiota of mice with antibiotics before inoculation with poliovirus, an enteric virus. Antibiotic-treated mice were less susceptible to poliovirus disease and supported minimal viral replication in the intestine. Exposure to bacteria or their N-acetylglucosamine-containing surface polysaccharides, including lipopolysaccharide and peptidoglycan, enhanced poliovirus infectivity. We found that poliovirus binds lipopolysaccharide, and exposure of poliovirus to bacteria enhanced host cell association and infection. The pathogenesis of reovirus, an unrelated enteric virus, also was more severe in the presence of intestinal microbes. These results suggest that antibiotic-mediated microbiota depletion diminishes enteric virus infection and that enteric viruses exploit intestinal microbes for replication and transmission.  相似文献   

4.
动物胃肠道中定植着数量巨大的肠道微生物,影响宿主动物的代谢和发育。肠道微生物在营养物质交换、信息传递和抵抗病原微生物入侵方面均发挥着重要的作用。依据定植部位,可以分成黏液层微生物和肠腔内微生物,Akkermansia muciniphila偏好地定植于肠道黏液层,对机体活动影响广泛。在肠道中,Akkermansia muciniphila可以特异地降解黏蛋白和低聚糖,分别产生短链脂肪酸和丙酸,在为宿主提供能量的同时也促进了自身的定植。而与此同时,机体黏蛋白的降解会促使宿主补偿产生更多的黏蛋白,进而降低宿主蛋白的沉积。Akkermansia muciniphila的定植还可减缓脂肪沉积,延缓糖尿病。在肠道微生态系统中,该菌群并没有严重的致病性,适宜丰度的Akkermansia muciniphila定植可以促进宿主免疫系统的发育,进而促进肠道健康。随着更多科学研究的展开,胃肠道微生物在机体中的重要性得到呈现。作为目前国内外的研究热点,Akkermansia muciniphila在机体肠道内的作用机制尚未完全明确。本文从Akkermansia muciniphila的定植环境、生理特性、对机体营养代谢的影响、与代谢性疾病及机体免疫相互作用等方面进行了综述,Akkermansia muciniphila为很有潜力的生物标记,应用于营养状态、代谢性疾病、免疫甚至癌症的评估和检测。  相似文献   

5.
To establish chronic infections, viruses must develop strategies to evade the host's immune responses. Many retroviruses, including mouse mammary tumor virus (MMTV), are transmitted most efficiently through mucosal surfaces rich in microbiota. We found that MMTV, when ingested by newborn mice, stimulates a state of unresponsiveness toward viral antigens. This process required the intestinal microbiota, as antibiotic-treated mice or germ-free mice did not transmit infectious virus to their offspring. MMTV-bound bacterial lipopolysaccharide triggered Toll-like receptor 4 and subsequent interleukin-6 (IL-6)-dependent induction of the inhibitory cytokine IL-10. Thus, MMTV has evolved to rely on the interaction with the microbiota to induce an immune evasion pathway. Together, these findings reveal the fundamental importance of commensal microbiota in viral infections.  相似文献   

6.
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.  相似文献   

7.
[目的]探讨草鱼肠道菌群与草鱼个体大小之间的相关性。[方法]采用DGGE方法对同一批孵化并在同一池塘中养殖的个体大小显著差异的草鱼肠道样品进行分析。[结果]无论大个体草鱼还是小个体草鱼,其肠道优势菌群均为厚壁菌门和变形菌门,但2组草鱼在其肠道菌群的结构和多样性等方面存在差异。大个体草鱼肠道中存在着更多比例的厚壁菌门以及具有纤维素降解能力的细菌,而小个体草鱼肠道中存在较多的潜在致病菌。[结论]草鱼肠道微生物可以作为内在因素影响草鱼的生长性能,这一结果也为进一步开发可促进草鱼生长性能的益生菌奠定了研究基础。  相似文献   

8.
The mammalian intestine harbors a beneficial microbiota numbering approximately 10(12) organisms per gram of colonic content. The host tolerates this tremendous bacterial load while maintaining the ability to efficiently respond to pathogenic organisms. In this study, we show that the Bacteroides use a mammalian-like pathway to decorate numerous surface capsular polysaccharides and glycoproteins with l-fucose, an abundant surface molecule of intestinal epithelial cells, resulting in the coordinated expression of this surface molecule by host and symbiont. A Bacteroides mutant deficient in the ability to cover its surface with L-fucose is defective in colonizing the mammalian intestine under competitive conditions.  相似文献   

9.
The enormous number of commensal bacteria in the lower intestine of vertebrates share abundant molecular patterns used for innate immune recognition of pathogenic bacteria. We show that, even though commensals are rapidly killed by macrophages, intestinal dendritic cells (DCs) can retain small numbers of live commensals for several days. This allows DCs to selectively induce IgA, which helps protect against mucosal penetration by commensals. The commensal-loaded DCs are restricted to the mucosal immune compartment by the mesenteric lymph nodes, which ensures that immune responses to commensal bacteria are induced locally, without potentially damaging systemic immune responses.  相似文献   

10.
Lineage relationship analysis of RORgammat+ innate lymphoid cells   总被引：1，自引：0，他引：1  
Lymphoid tissue-inducer (LTi) cells initiate the development of lymphoid tissues through the activation of local stromal cells in a process similar to inflammation. LTi cells express the nuclear hormone receptor RORγt, which also directs the expression of the proinflammatory cytokine interleukin-17 in T cells. We show here that LTi cells are part of a larger family of proinflammatory RORγt(+) innate lymphoid cells (ILCs) that differentiate from distinct fetal liver RORγt(+) precursors. The fate of RORγt(+) ILCs is determined by mouse age, and after birth, favors the generation of cells involved in intestinal homeostasis and defense. Contrary to RORγt(+) T cells, however, RORγt(+) ILCs develop in the absence of microbiota. Our study indicates that RORγt(+) ILCs evolve to preempt intestinal colonization by microbial symbionts.  相似文献   

11.
Shin SC  Kim SH  You H  Kim B  Kim AC  Lee KA  Yoon JH  Ryu JH  Lee WJ 《Science (New York, N.Y.)》2011,334(6056):670-674
The symbiotic microbiota profoundly affect many aspects of host physiology; however, the molecular mechanisms underlying host-microbe cross-talk are largely unknown. Here, we show that the pyrroloquinoline quinone-dependent alcohol dehydrogenase (PQQ-ADH) activity of a commensal bacterium, Acetobacter pomorum, modulates insulin/insulin-like growth factor signaling (IIS) in Drosophila to regulate host homeostatic programs controlling developmental rate, body size, energy metabolism, and intestinal stem cell activity. Germ-free animals monoassociated with PQQ-ADH mutant bacteria displayed severe deregulation of developmental and metabolic homeostasis. Importantly, these defects were reversed by enhancing host IIS or by supplementing the diet with acetic acid, the metabolic product of PQQ-ADH.  相似文献   

12.
The intestinal microflora, typically equated with bacteria, influences diseases such as obesity and inflammatory bowel disease. Here, we show that the mammalian gut contains a rich fungal community that interacts with the immune system through the innate immune receptor Dectin-1. Mice lacking Dectin-1 exhibited increased susceptibility to chemically induced colitis, which was the result of altered responses to indigenous fungi. In humans, we identified a polymorphism in the gene for Dectin-1 (CLEC7A) that is strongly linked to a severe form of ulcerative colitis. Together, our findings reveal a eukaryotic fungal community in the gut (the "mycobiome") that coexists with bacteria and substantially expands the repertoire of organisms interacting with the intestinal immune system to influence health and disease.  相似文献   

13.
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.  相似文献   

14.
为了探究稻田和池塘养殖模式对中华绒螯蟹(Eriocheir sinensis)肠道菌群、免疫力和肌肉风味影响,选取同一批次稻田和池塘的中华绒螯蟹在5月和10月对其肠道菌群、免疫酶活和肌肉游离氨基酸进行测定。结果表明：中华绒螯蟹肠道优势菌群为软壁菌门、拟杆菌门、变形菌门和厚壁菌门。在季节和养殖模式均对蟹的肠道菌群造成影响的情况下,季节变化对菌群变化的影响更大。从5月到10月,稻田养殖模式下中华绒螯蟹肠道菌群的丰富度和多样性均出现上升趋势,而池塘养殖模式下肠道菌群的丰富度和多样性则无显著变化。两种养殖模式下中华绒螯蟹肠道中的SOD (超氧化物歧化酶)在5月的活性均高于10月(P <0.05);在10月,池塘模式下的免疫酶活性LZM（溶菌酶）和ACP（酸性磷酸酶）显著高于稻田模式(P< 0.05)。各组肌肉中均检测出17种游离氨基酸,呈味氨基酸中甜味氨基酸含量(TSAA)>总苦味氨基酸(TBAA)>总鲜味氨基酸(TUAA),且池塘养殖模式下中华绒螯蟹肌肉中TSAA和总游离氨基酸TFAA高于稻田养殖模式下含量(P< 0.05)。因此,池塘养殖模式较稻田养殖模式下的中华绒螯蟹肠道菌群时间上更稳定,免疫酶活更强,肌肉风味更优。  相似文献   

15.
Ryu JH  Kim SH  Lee HY  Bai JY  Nam YD  Bae JW  Lee DG  Shin SC  Ha EM  Lee WJ 《Science (New York, N.Y.)》2008,319(5864):777-782
Although commensalism with gut microbiota exists in all metazoans, the host factors that maintain this homeostatic relationship remain largely unknown. We show that the intestinal homeobox gene Caudal regulates the commensal-gut mutualism by repressing nuclear factor kappa B-dependent antimicrobial peptide genes. Inhibition of Caudal expression in flies via RNA interference led to overexpression of antimicrobial peptides, which in turn altered the commensal population within the intestine. In particular, the dominance of one gut microbe, Gluconobacter sp. strain EW707, eventually led to gut cell apoptosis and host mortality. However, restoration of a healthy microbiota community and normal host survival in the Caudal-RNAi flies was achieved by reintroduction of the Caudal gene. These results reveal that a specific genetic deficiency within a host can profoundly influence the gut commensal microbial community and host physiology.  相似文献   

16.
Commensal host-bacterial relationships in the gut   总被引：2，自引：0，他引：2  
One potential outcome of the adaptive coevolution of humans and bacteria is the development of commensal relationships, where neither partner is harmed, or symbiotic relationships, where unique metabolic traits or other benefits are provided. Our gastrointestinal tract is colonized by a vast community of symbionts and commensals that have important effects on immune function, nutrient processing, and a broad range of other host activities. The current genomic revolution offers an unprecedented opportunity to identify the molecular foundations of these relationships so that we can understand how they contribute to our normal physiology and how they can be exploited to develop new therapeutic strategies.  相似文献   

17.
Dendritic cells (DCs) and macrophages are critical to innate and adaptive immunity to the intestinal bacterial microbiota. Here, we identify a myeloid-derived mucosal DC in mice, which populates the entire lamina propria of the small intestine. Lamina propria DCs were found to depend on the chemokine receptor CX3CR1 to form transepithelial dendrites, which enable the cells to directly sample luminal antigens. CX3CR1 was also found to control the clearance of entero-invasive pathogens by DCs. Thus, CX3CR1-dependent processes, which control host interactions of specialized DCs with commensal and pathogenic bacteria, may regulate immunological tolerance and inflammation.  相似文献   

18.
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。  相似文献   

19.
Plague bacteria target immune cells during infection   总被引：1，自引：0，他引：1  
The plague is caused by the bacterium Yersinia pestis. Plague bacteria are thought to inject effector Yop proteins into host cells via the type III pathway. The identity of the host cells targeted for injection during plague infection is unknown. We found, using Yop beta-lactamase hybrids and fluorescent staining of live cells from plague-infected animals, that Y. pestis selected immune cells for injection. In vivo, dendritic cells, macrophages, and neutrophils were injected most frequently, whereas B and T lymphocytes were rarely selected. Thus, it appears that Y. pestis disables these cell populations to annihilate host immune responses during plague.  相似文献   

20.
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