肠道微生物与人体健康研究进展

人类肠道中定居着许多对宿主有益的微生物,包括细菌、病毒、真核生物等,它们在肠道内能与其他微生物及免疫系统相互作用,对人体健康具有重要影响,被称为"被遗忘的器官",它们的基因组也被誉为人类的"第二基因组",与人体的能量代谢及物质代谢有关。本文总结了人体肠道中病毒、真核生物、细菌和宿主免疫系统的相互作用,微生物群的失衡可能导致的疾病如肥胖和克罗恩病等,以及微生物环境在人体内的成熟过程,期望有助于诊断和治疗与肠道微生物失衡相关的疾病。     

Evidence for host effect on the intestinal microbiota of whitefish (Coregonus sp.) species pairs and their hybrids

Investigating relationships between microbiota and their host is essential toward a full understanding of how animal adapt to their environment. Lake Whitefish offers a powerful system to investigate processes of adaptive divergence where the dwarf, limnetic species evolved repeatedly from the normal, benthic species. We compared the transient intestinal microbiota between both species from the wild and in controlled conditions, including their reciprocal hybrids. We sequenced the 16s rRNA gene V3‐V4 regions to (a) test for parallelism in the transient intestinal microbiota among sympatric pairs, (b) test for transient intestinal microbiota differences among dwarf, normal, and hybrids reared under identical conditions, and (c) compare intestinal microbiota between wild and captive whitefish. A significant host effect on microbiota taxonomic composition was observed when all lakes were analyzed together and in three of the five species pairs. In captive whitefish, host effect was also significant. Microbiota of both reciprocal hybrids fell outside of that observed in the parental forms. Six genera formed a bacterial core which was present in captive and wild whitefish, suggesting a horizontal microbiota transmission. Altogether, our results complex interactions among the host, the microbiota, and the environment, and we propose that these interactions define three distinct evolutionary paths of the intestinal microbiota.     

Role of the microbiota in circadian rhythms of the host

ABSTRACT

Life for meta-organisms is based on a strong relationship between gut bacteria and body cells. This review summarizes to what extent the microbiota can influence host circadian rhythms via a literature review on the topic. The results show that microbiota can influence the host’s circadian gene expression through direct interactions via immunoreceptors and microbiota-derived metabolites, especially in peripheral tissues. Noteworthy metabolites that are only attributable to the microbiota are short-chain fatty acids and unconjugated bile acids. The microbiota also serves as a mediator for the interplay between the host’s diet and circadian rhythmicity. This work furthermore displays that the microbiota is subject to diurnal variations in terms of structure and function and that the host and the host’s diet influence these fluctuations. As most of these results originate in mouse models, we hope this work stimulates further research in human derived tissue to verify these conclusions.     

Gut microbiota instead of host genotype drive the specificity in the interaction of a natural host-parasite system

Specific interactions between parasite genotypes and host genotypes (G_p × G_h) are commonly found in invertebrate systems, but are largely lacking a mechanistic explanation. The genotype of invertebrate hosts can be complemented by the genomes of microorganisms living on or within the host (‘microbiota’). We investigated whether the bacterial gut microbiota of bumble bees (Bombus terrestris) can account for the specificity of interactions between individuals from different colonies (previously taken as host genotype proxy) and genotypes of the parasite Crithidia bombi. For this, we transplanted the microbiota between individuals of six colonies. Both the general infection load and the specific success of different C. bombi genotypes were mostly driven by the microbiota, rather than by worker genotype. Variation in gut microbiota can therefore be responsible for specific immune phenotypes and the evolution of gut parasites may be driven by interactions with ‘microbiota types’ as well as with host genotypes.     

Microbiota-immune system interaction: an uneasy alliance

An estimated 100 trillion microbes colonize human beings, with the majority of organisms residing in the intestines. This microbiota impacts host nutrition, protection, and gut development. Alterations in microbiota composition are associated with susceptibility to various infectious and inflammatory gut diseases. The mucosal surface is not a static barrier that simply prevents microbial invasion but a critical interface for microbiota-immune system interactions. Recent work suggests that dynamic interactions between microbes and the host immune system at the mucosal surface inform immune responses both locally and systemically. This review focuses on intestinal microbiota-immune interactions leading to intestinal homeostasis, and show that these interactions at the GI mucosal surface are critical for driving both protective and pathological immune responses systemically.     

Recently duplicated sesterterpene (C25) gene clusters in Arabidopsis thaliana modulate root microbiota

Land plants co-speciate with a diversity of continually expanding plant specialized metabolites(PSMs) and root microbial communities(microbiota). Homeostatic interactions between plants and root microbiota are essential for plant survival in natural environments. A growing appreciation of microbiota for plant health is fuelling rapid advances in genetic mechanisms of controlling microbiota by host plants. PSMs have long been proposed to mediate plant and single microbe interactions. However,the effects of PSMs, especially those evolutionarily new PSMs, on root microbiota at community level remain to be elucidated.Here, we discovered sesterterpenes in Arabidopsis thaliana, produced by recently duplicated prenyltransferase-terpene synthase(PT-TPS) gene clusters, with neo-functionalization. A single-residue substitution played a critical role in the acquisition of sesterterpene synthase(sesterTPS) activity in Brassicaceae plants. Moreover, we found that the absence of two root-specific sesterterpenoids, with similar chemical structure, significantly affected root microbiota assembly in similar patterns. Our results not only demonstrate the sensitivity of plant microbiota to PSMs but also establish a complete framework of host plants to control root microbiota composition through evolutionarily dynamic PSMs.     

肠道微生物群与药物相互作用的研究进展

药物的代谢是机体对药物处置过程的关键步骤,而肠道作为机体中重要的微生态系统,其在药物代谢方面的作用至关重要。肠道微生物群能够对各种药物等外源化合物进行生物转化、积累,并改变这些物质的活性和毒性,从而影响宿主机体对它们的反应。肠道微生物群与药物之间的相互作用相当复杂,亟待更多更加深入、全面的发掘和研究。近年来,随着人们对肠道微生物群代谢及其与药物互作关系,肠道菌-宿主共代谢认知的不断深化,越来越多的研究表明肠道微生物在药代动力学中扮演重要角色。本文通过调研、整理、归纳和总结国内外相关文献资料,对机体肠道微生物的分类、功能,几种常用药物对肠道微生物的影响以及肠道菌群对药物的代谢作用效果与几个主要的机制进行了梳理和综述,并讨论了微生物和药物之间的双向互作。有利于增进对微生物群影响药物疗效及其代谢途径和机制的了解,提高调控肠道微生物改善治疗的可能性,为指导临床合理用药、精准用药、个体化治疗、药物的评价和新药研发等提供科学参考。     

Interactions between multiple helminths and the gut microbiota in wild rodents

The gut microbiota is vital to host health and, as such, it is important to elucidate the mechanisms altering its composition and diversity. Intestinal helminths are host immunomodulators and have evolved both temporally and spatially in close association with the gut microbiota, resulting in potential mechanistic interplay. Host–helminth and host–microbiota interactions are comparatively well-examined, unlike microbiota–helminth relationships, which typically focus on experimental infection with a single helminth species in laboratory animals. Here, in addition to a review of the literature on helminth–microbiota interactions, we examined empirically the association between microbiota diversity and composition and natural infection of multiple helminth species in wild mice (Apodemus flavicollis), using 16S rRNA gene catalogues (metataxonomics). In general, helminth presence is linked with high microbiota diversity, which may confer health benefits to the host. Within our wild rodent system variation in the composition and abundance of gut microbial taxa associated with helminths was specific to each helminth species and occurred both up- and downstream of a given helminth''s niche (gut position). The most pronounced helminth–microbiota association was between the presence of tapeworms in the small intestine and increased S24–7 (Bacteroidetes) family in the stomach. Helminths clearly have the potential to alter gut homeostasis. Free-living rodents with a diverse helminth community offer a useful model system that enables both correlative (this study) and manipulative inference to elucidate helminth–microbiota interactions.     

The gut microbiota and its interactions with cardiovascular disease

The intestine is colonized by a considerable community of microorganisms that cohabits within the host and plays a critical role in maintaining host homeostasis. Recently, accumulating evidence has revealed that the gut microbial ecology plays a pivotal role in the occurrence and development of cardiovascular disease (CVD). Moreover, the effects of imbalances in microbe–host interactions on homeostasis can lead to the progression of CVD. Alterations in the composition of gut flora and disruptions in gut microbial metabolism are implicated in the pathogenesis of CVD. Furthermore, the gut microbiota functions like an endocrine organ that produces bioactive metabolites, including trimethylamine/trimethylamine N-oxide, short-chain fatty acids and bile acids, which are also involved in host health and disease via numerous pathways. Thus, the gut microbiota and its metabolic pathways have attracted growing attention as a therapeutic target for CVD treatment. The fundamental purpose of this review was to summarize recent studies that have illustrated the complex interactions between the gut microbiota, their metabolites and the development of common CVD, as well as the effects of gut dysbiosis on CVD risk factors. Moreover, we systematically discuss the normal physiology of gut microbiota and potential therapeutic strategies targeting gut microbiota to prevent and treat CVD.     

Transgenerational developmental effects of species‐specific,maternally transmitted microbiota in Onthophagus dung beetles

1. The significance of host–microbe interactions is increasingly appreciated across biological disciplines, yet to what extent these interactions influence developmental outcomes within and across generations remains poorly understood. 2. This study investigated the putative role of host–microbe interactions in the adaptive diversification of Onthophagus dung beetles, one of the most species‐rich and ecologically successful genera of insects. Onthophagus mothers vertically transmit growth‐ and fitness‐enhancing gut symbionts to their offspring through a faecal secretion known as the pedestal. 3. Pedestals were reciprocally exchanged between two ecologically similar congeneric Onthophagus species to assess the degree to which pedestal microbiota from one species can substitute for those of another. 4. It was found that the presence of a heterospecific pedestal delays development and increases mortality, and that the fitness costs of non‐host‐specific microbiota are maintained transgenerationally. 5. Collectively, these results support the hypothesis that Onthophagus beetles maintain, interact with, and are dependent upon host species‐specific microbial communities to support normal growth and development. The implications of these results are discussed in the context of host microbiota coevolution.     

Commensal microbial regulation of natural killer T cells at the frontiers of the mucosal immune system

The commensal microbiota co-exists in a mutualistic relationship with its human host. Commensal microbes play critical roles in the regulation of host metabolism and immunity, while microbial colonization, conversely, is under control of host immunity and metabolic pathways. These interactions are of central importance to the maintenance of homeostasis at mucosal surfaces and their perturbation can provide the basis for atopic and chronic inflammatory diseases such as asthma and inflammatory bowel disease (IBD). Recent evidence has revealed that natural killer T (NKT) cells, a subgroup of T cells which recognizes self and microbial lipid antigens presented by CD1d, are key mediators of host-microbial interactions. Mucosal and systemic NKT cell development is under control of the commensal microbiota, while CD1d regulates microbial colonization and influences the composition of the intestinal microbiota. Here, we outline the mechanisms of bidirectional cross-talk between the microbiota and CD1d-restricted NKT cells and discuss how a perturbation of these processes can contribute to the pathogenesis of immune-mediated disorders at mucosal surfaces.     

Bacterial microbiota similarity between predators and prey in a blue tit trophic network

Trophic networks are composed of many organisms hosting microbiota that interact with their hosts and with each other. Yet, our knowledge of the factors driving variation in microbiota and their interactions in wild communities is limited. To investigate the relation among host microbiota across a trophic network, we studied the bacterial microbiota of two species of primary producers (downy and holm oaks), a primary consumer (caterpillars), and a secondary consumer (blue tits) at nine sites in Corsica. To quantify bacterial microbiota, we amplified 16S rRNA gene sequences in blue tit feces, caterpillars, and leaf samples. Our results showed that hosts from adjacent trophic levels had a more similar bacterial microbiota than hosts separated by two trophic levels. Our results also revealed a difference between bacterial microbiota present on the two oak species, and among leaves from different sites. The main drivers of bacterial microbiota variation within each trophic level differed across spatial scales, and sharing the same tree or nest box increased similarity in bacterial microbiota for caterpillars and blue tits. This study quantifies host microbiota interactions across a three-level trophic network and illustrates how the factors shaping bacterial microbiota composition vary among different hosts.Subject terms: Food webs, Microbial ecology     

肠道微生物与骨质疏松相关性的研究进展

随着人口老龄化问题的加剧,骨质疏松症的高发生率降低了人们的生活质量。越来越多的证据表明,肠道微生物群与骨代谢联系密切,肠道微生物群稳态的破坏会导致宿主的病理生理反应,从而引起骨质疏松。通过研究两者之间的相互作用,或许能为骨质疏松症的预防及相关诊疗提供有价值的帮助。本文就目前肠道微生物与骨质疏松症相关机制和主要治疗的研究现状作一综述。     

肠道微生态系统及其与宿主的协同进化

肠道微生态系统是寄生在宿主肠道内的微生物的总和。微生物进入肠道后,通过一个复杂的过程形成群落,与宿主之间相互作用,形成共生关系。宿主客观上为微生物提供生存和进化场所,微生态系统为宿主提供营养物质、刺激肠道组织的发育、刺激宿主肠道免疫系统的发育、影响宿主能量代谢、协助宿主降解有毒物质、影响宿主生殖活动和寿命等功能。作为一个进化的系统,微生态系统的物种多样性和丰富度对维持宿主正常生理功能具有重要作用,但同时又受宿主的影响,物种间相互作用和宿主-微生物间的相互作用是微生态系统进化的动力。进化主要表现在微生物和宿主基因组上发生适应性变化。因此,系统生态学的理论对理解肠道微生态系统的运行机制和临床应用具有重要指导作用。     

Transient adult microbiota,gut homeostasis and longevity: Novel insights from the Drosophila model

In the last decade, Drosophila has emerged as a useful model to study host–microbiota interactions, creating an active research field with prolific publications. In the last 2 years, several studies contributed to a better understanding of the dynamic nature of microbiota composition and its impact on gut immunity and intestinal tissue homeostasis. These studies depicted the mechanisms by which microbiota regulates gut homeostasis to modulate host fitness and lifespan. Moreover, the latest findings demonstrating that the gut is a physiologically and histologically compartmentalized organ brought fresh perspectives to study the region-specific nature of the interactions between the commensal microbes and the intestinal tissue, and consequences of these interactions on overall host biology.     

Shifting the balance: antibiotic effects on host-microbiota mutualism

Antibiotics have been used effectively as a means to treat bacterial infections in humans and animals for over half a century. However, through their use, lasting alterations are being made to a mutualistic relationship that has taken millennia to evolve: the relationship between the host and its microbiota. Host-microbiota interactions are dynamic; therefore, changes in the microbiota as a consequence of antibiotic treatment can result in the dysregulation of host immune homeostasis and an increased susceptibility to disease. A better understanding of both the changes in the microbiota as a result of antibiotic treatment and the consequential changes in host immune homeostasis is imperative, so that these effects can be mitigated.     

Evidence for a core gut microbiota in the zebrafish

Experimental analysis of gut microbial communities and their interactions with vertebrate hosts is conducted predominantly in domesticated animals that have been maintained in laboratory facilities for many generations. These animal models are useful for studying coevolved relationships between host and microbiota only if the microbial communities that occur in animals in lab facilities are representative of those that occur in nature. We performed 16S rRNA gene sequence-based comparisons of gut bacterial communities in zebrafish collected recently from their natural habitat and those reared for generations in lab facilities in different geographic locations. Patterns of gut microbiota structure in domesticated zebrafish varied across different lab facilities in correlation with historical connections between those facilities. However, gut microbiota membership in domesticated and recently caught zebrafish was strikingly similar, with a shared core gut microbiota. The zebrafish intestinal habitat therefore selects for specific bacterial taxa despite radical differences in host provenance and domestication status.     

Microbiology and immunology: An ideal partnership for a tango at the gut surface—A tribute to Philippe Sansonetti

Over the past 20 years, the highly dynamic interactions that take place between hosts and the gut microbiota have emerged as a major determinant in health and disease. The complexity of the gut microbiota represents, however, a considerable challenge, and reductionist approaches are indispensable to define the contribution of individual bacteria to host responses and to dissect molecular mechanisms. In this tribute to Philippe Sansonetti, I would like to show how rewarding collaborations with microbiologists have guided our team of immunologists in the study of host–microbiota interactions and, thanks to the use of controlled colonisation experiments in gnotobiotic mice, toward the demonstration that segmented filamentous bacteria (SFB) are indispensable to drive the post‐natal maturation of the gut immune barrier in mice. The work led with Philippe Sansonetti to set up in vitro culture conditions has been one important milestone that laid the ground for in‐depth characterization of the molecular attributes of this unusual symbiont. Recent suggestions that SFB may be present in the human microbiota encourage further cross‐fertilising interactions between microbiologists and immunologists to define whether results from mice can be translated to humans and, if so, how SFB may be used to promote human intestinal defences against enteropathogens. Nurturing the competences to pursue this inspiring project is one legacy of Philippe Sansonetti.     

The gut microbiota in the metagenomics era: sometimes a friend, sometimes a foe

The normal intestinal microflora (microbiota) represents a complex, dynamic, and diverse collection of microorganisms, which usually inhabit the gastrointestinal tract. Normally, between this flora and the human host a mutually beneficial long-term symbiotic relationship is established, where the host contributes essential nutrients necessary for the survival of the microbiota and the latter fulfils multiple roles in host nutrition and development. Several achievements have recently converged to renew interest in studying the normal gut microbiota: the development of molecular methods of studying the microbial communities, the improved understanding of host-microbe interactions in health and disease, and the potential for therapeutic manipulation of the microbiota. We present recent data concerning the molecular technologies of studying the microbiota and new findings regarding the composition of the normal flora. We underline the beneficial activities of the gut flora on the human host. We emphasize the recent findings in the alterations of the microbiota in various medical conditions (celiac disease, irritable bowel syndrome, obesity, colorectal cancer, allergic disorders, and especially inflammatory bowel diseases). The results of these new studies suggest that changes of the microbiota could be linked to the etiopathogenesis of these diseases. These outstanding findings could be used for further diagnostic tools and/or therapy.