早产儿生命早期肠道菌群的建立及其相关疾病研究进展

肠道菌群是一个数量庞大且种类复杂的微生物群落,是人类的"第二基因组",同时又是一个被遗忘的"器官",参与调控宿主生理及病理过程.随着检测技术的不断提高,肠道菌群的研究已经成为了热点,其与各个系统疾病关系的研究也不断深入.生命早期(包括胎儿期和婴幼儿期)是婴幼儿尤其是早产儿肠道菌群定植及演替的主要阶段,具备动态变化的特征...     

益生菌及益生元调节骨代谢的研究进展

骨质疏松症已成为威胁中老年人健康的主要疾病之一,越来越多的人受到该病症的危害.肠道菌群是定殖在机体肠道内,与宿主形成共生关系的微生物,对宿主的免疫及代谢等产生重要影响,研究发现,肠道菌群与骨代谢之间存在密切关系,本文从肠道菌群与免疫、骨代谢与免疫、肠道菌群与骨代谢、益生菌及益生元调节骨代谢等几个方面阐述,肠道菌群有望成为骨质疏松症治疗的一个新靶点,通过益生菌或益生元来干预肠道菌群组成,进而调节免疫系统状态,抑制促炎因子的生成,从而降低骨吸收作用,达到预防和治疗骨质疏松症的目的.     

基于菌群调控下的天然植物活性成分与全食态健康效用评价

肠道菌群与人体共同协作,菌群在帮助宿主对食物中的营养成分进行深入消化与利用的同时,也一同分享宿主为其提供的生存空间与营养物质,这是微生物与宿主之间形成的一种互利共生的特殊共存方式。这样的精妙结合,不仅使得微生物在人体中形成了固有的菌群结构,得到赖以生存的生物基位,也通过自身的功能代谢以及群体信号,为宿主在免疫、营养等方面提供所必需的调节与支撑。围绕药食同源天然植物的健康作用研究,目前大多着眼于对其功能组分的分离提取与活性评价。如植物多糖、多酚与黄酮等活性功能成分。然而在传统中医药中,植物多以全食态进行复配应用。目前在菌群水平研究中发现,对于影响人体健康水平的菌群模式并非固定且依赖于某一单菌种变化,微生物之间的生态竞争与代谢调控均以群体的方式与宿主持续进行共进化。药食同源天然植物,对菌群的调节作用主要还是依靠其全食态,这也从菌群这个微观生态环境的角度为传统中医学理论中对于中药食材即天然植物全食状态下的药效提供了重要佐证。因此,对于药食同源天然植物的开发与利用,应当结合菌群整体的调控进行分析,并对其全食状态与活性功能组分有充分的认识与评价。     

人类肠道菌群与疾病关系的元基因组学研究进展

人体的生理健康除受自身基因的调控外,还受到肠道菌群的影响。人体肠道内的细菌有1 000～1 150种,其中160种为优势菌种,存在不同类型的生态学相互作用。肠道细菌的300多万个基因被视为人类的"第二基因组",在正常人体健康状态下,肠道微生物种群处于平衡状态,而在宿主患病期,菌群失调或紊乱。采用元基因组学研究能在更高更复杂层次上揭示肠道菌群之间的生命运动规律。本文系统综述了元基因组学对肠道菌群与肥胖、糖尿病、炎症性肠病等疾病之间关系的研究进展。     

念珠菌适应宿主环境压力的共生机制研究进展

作为人体微生物菌群中真菌菌群的一个重要组成部分,念珠菌通常定植于人体的众多生态位,在免疫系统功能正常的健康人群中与宿主保持共生状态。为适应宿主体内复杂多变的环境,拮抗宿主免疫系统的攻击,以及应对其他微生物菌群的竞争等诸多生存压力,念珠菌进化出一系列极为有效的应对机制以维持其在宿主体内的共生。本文总结了念珠菌通过形态转换、环境适应、免疫调节以及与其他微生物菌群相互作用等策略应对宿主环境生存压力的分子机制,重点阐述了念珠菌、宿主免疫系统以及微生物菌群三者之间的相互作用和相互平衡对于念珠菌实现成功定植和共生的重要意义。     

肺部菌群与呼吸道疾病的相互关系

由于呼吸道黏膜免疫系统具有很好的防御保护作用和强大的清除病原体的能力,过去学术界曾经一度认为健康机体的肺是无菌的。随着不依赖于体外培养的第二代测序技术的发展,关于肺部共生微生物的结构组成及其免疫调节功能的研究越来越受重视。肺部菌群的结构组成与出生方式、饮食结构、生活环境和抗生素使用等多种因素有关,生命早期的肺部菌群的形成和发育会影响全生命周期的呼吸道疾病的发生和发展。肺部菌群通过与宿主免疫系统相互作用调节肺部免疫稳态,还可以与肠道菌群、呼吸道病毒相互作用影响呼吸道感染。因此,干预生命早期肺部菌群的结构组成可以成为预防和控制呼吸道疾病的有效策略和新靶点。     

microRNA 对宿主和肠道微生物互作的调控

摘要:肠道内环境是宿主和肠道微生物菌群互作的结果,肠道菌群一方面通过抗原物质调节肠道组织的免疫稳定,另一方面,肠道菌群参与糖、脂、蛋白质代谢,产生的代谢产物能够调控细菌营养代谢、群体结构和肠道组织的营养吸收等。microRNA是宿主细胞内调控基因表达的重要因子,肠道微生物菌群不仅调控宿主mRNA的转录,同时也影响某些基因的转录后修饰。研究表明,肠道菌群通过与宿主肠道组织互作,调节肠上皮组织内某些参与炎症应答和屏障功能的microRNA 的表达。本文介绍了肠道微生物与宿主互作的基本内容,对microRNA在肠道微生物与宿主互作和肠道健康中的调节进行综述。     

鱼类肠道微生物与宿主免疫系统相互作用研究进展

鱼类肠道中存在大量微生物,对于维持宿主健康具有重要作用。鱼类免疫系统能够监视并调控肠道微生物组成,维持肠道菌群稳态。同时,鱼类肠道共生微生物调节鱼类免疫系统,抑制病原微生物的过度增殖,保证宿主的健康。本文回顾了鱼类肠道微生物与宿主免疫系统相互作用的研究进展,重点介绍了宿主免疫系统识别肠道微生物、塑造肠道菌群以及益生菌对宿主免疫和肠道菌群的调控等,提出了理想的益生菌应该来自动物自身胃肠道,生产中应谨慎选用非宿主来源的益生菌,以期为推动鱼类肠道功能微生物开发和应用提供理论支撑。     

肠道菌群功能与影响因素研究进展

人体肠道作为一种营养丰富的天然环境有多达100兆个微生物,其中绝大多数存于结肠内,密度接近1011~1012/m L。人类肠道内的微生物多样性是微生物菌落和宿主共同进化的结果,自然选择和进化使肠道菌群与宿主处于一种动态平衡且稳定的关系。文章综述了肠道菌群对宿主可能产生的影响以及引起肠道菌群发生改变的某些因素,肠道微生物影响宿主的代谢、营养吸收、免疫功能以及神经功能调节,而饮食及其他条件又能引起肠道菌群的改变。深入分析肠道菌群的具体结构、探索不同微生物在宿主体内究竟发挥着怎样的作用以及如何充分利用微生物的不同特性改善人类健康应成为今后研究的重点方向。     

鸡肠道微生物菌群的建立发育、分布和生理学意义

鸡的胃肠道具有复杂的微生物菌群,该微生物菌群与宿主的肠道和整体健康密切相关,为了全面揭示鸡肠道微生物菌群的组成及其功能,本文对鸡肠道微生物菌群的建立发育、各肠段群落的分布及其生理学意义进行综述,从而为鸡肠道功能菌株的分离及有效利用,合理调控微生物菌群-宿主相互作用,提高饲料转化率和改善肠道健康提供理论依据。     

Review: The development of the gastrointestinal tract microbiota and intervention in neonatal ruminants

The complex microbiome colonizing the gastrointestinal tract (GIT) of ruminants plays an important role in the development of the immune system, nutrient absorption and metabolism. Hence, understanding GIT microbiota colonization in neonatal ruminants has positive impacts on host health and productivity. Microbes rapidly colonize the GIT after birth and gradually develop into a complex microbial community, which allows the possibility of GIT microbiome manipulation to enhance newborn health and growth and perhaps induce lasting effects in adult ruminants. This paper reviews recent advances in understanding how host-microbiome interactions affect the GIT development and health of neonatal ruminants. Following initial GIT microbiome colonization, continuous exposure to host-specific microorganisms is necessary for GIT development and immune system maturation. Furthermore, the early GIT microbial community structure is significantly affected by early life events, such as maternal microbiota exposure, dietary changes, age and the addition of prebiotics, probiotics and synbiotics, supporting the idea of microbial programming in early life. However, the time window in which interventions can optimally improve production and reduce gastrointestinal disease as well as the role of key host-specific microbiota constituents and host immune regulation requires further study.     

Top‐down systems biology integration of conditional prebiotic modulated transgenomic interactions in a humanized microbiome mouse model

Gut microbiome–host metabolic interactions affect human health and can be modified by probiotic and prebiotic supplementation. Here, we have assessed the effects of consumption of a combination of probiotics (Lactobacillus paracasei or L. rhamnosus) and two galactosyl‐oligosaccharide prebiotics on the symbiotic microbiome–mammalian supersystem using integrative metabolic profiling and modeling of multiple compartments in germ‐free mice inoculated with a model of human baby microbiota. We have shown specific impacts of two prebiotics on the microbial populations of HBM mice when co‐administered with two probiotics. We observed an increase in the populations of Bifidobacterium longum and B. breve, and a reduction in Clostridium perfringens, which were more marked when combining prebiotics with L. rhamnosus. In turn, these microbial effects were associated with modulation of a range of host metabolic pathways observed via changes in lipid profiles, gluconeogenesis, and amino‐acid and methylamine metabolism associated to fermentation of carbohydrates by different bacterial strains. These results provide evidence for the potential use of prebiotics for beneficially modifying the gut microbial balance as well as host energy and lipid homeostasis.     

Gut dysbacteriosis and intestinal disease: mechanism and treatment

The gut microbiome functions like an endocrine organ, generating bioactive metabolites, enzymes or small molecules that can impact host physiology. Gut dysbacteriosis is associated with many intestinal diseases including (but not limited to) inflammatory bowel disease, primary sclerosing cholangitis-IBD, irritable bowel syndrome, chronic constipation, osmotic diarrhoea and colorectal cancer. The potential pathogenic mechanism of gut dysbacteriosis associated with intestinal diseases includes the alteration of composition of gut microbiota as well as the gut microbiota–derived signalling molecules. The many correlations between the latter and the susceptibility for intestinal diseases has placed a spotlight on the gut microbiome as a potential novel target for therapeutics. Currently, faecal microbial transplantation, dietary interventions, use of probiotics, prebiotics and drugs are the major therapeutic tools utilized to impact dysbacteriosis and associated intestinal diseases. In this review, we systematically summarized the role of intestinal microbiome in the occurrence and development of intestinal diseases. The potential mechanism of the complex interplay between gut dysbacteriosis and intestinal diseases, and the treatment methods are also highlighted.     

Gut microbiome in tumorigenesis and therapy of colorectal cancer

Colorectal cancer (CRC) is the malignant tumor with the highest incidence in the digestive system, and the gut microbiome plays a crucial role in CRC tumorigenesis and therapy. The gastrointestinal tract is the organ harboring most of the microbiota in humans. Changes in the gut microbiome in CRC patients suggest possible host–microbe interactions, thereby hinting the potential tumorigenesis, which provides new perspective for preventing, diagnosing, or treating CRC. In this review, we discuss the effects of gut microbiome dysbiosis on CRC, and reveal the mechanisms by which gut microbiome dysbiosis leads to CRC. Gut microbiome modulation with the aim to reverse the established gut microbial dysbiosis is a novel strategy for the prevention and treatment of CRC. In addition, this review summarizes that probiotic antagonize CRC tumorigenesis by protecting intestinal barrier function, inhibiting cancer cell proliferation, resisting oxidative stress, and enhancing host immunity. Finally, we highlight clinical applications of the gut microbiome, such as gut microbiome analysis-based biomarker screening and prediction, and microbe modulation-based CRC prevention, treatment enhancement, and treatment side effect reduction. This review provides the reference for the clinical application of gut microbiome in the prevention and treatment of CRC.     

Environmental plasticity and colonisation history in the Atlantic salmon microbiome: A translocation experiment

Microbial communities associated with the gut and the skin are strongly influenced by environmental factors, and can rapidly adapt to change. Historical processes may also affect the microbiome. In particular, variation in microbial colonisation in early life has the potential to induce lasting effects on microbial assemblages. However, little is known about the relative extent of microbiome plasticity or the importance of historical colonisation effects following environmental change, especially for nonmammalian species. To investigate this we performed a reciprocal translocation of Atlantic salmon between artificial and semi‐natural conditions. Wild and hatchery‐reared fry were transferred to three common garden experimental environments for 6 weeks: standard hatchery conditions, hatchery conditions with an enriched diet, and simulated wild conditions. We characterized the faecal and skin microbiome of individual fish before and after the environmental translocation, using a BACI (before‐after‐control‐impact) design. We found evidence of extensive microbiome plasticity for both the gut and skin, with the greatest changes in alpha and beta diversity associated with the largest changes in environment and diet. Microbiome richness and diversity were entirely determined by environment, with no detectable effects of fish origin, and there was also a near‐complete turnover in microbiome structure. However, we also identified, for the first time in fish, evidence of historical colonisation effects reflecting early‐life experience, including ASVs characteristic of captive rearing. These results have important implications for host adaptation to local selective pressures, and highlight how conditions experienced during early life can have a long‐term influence on the microbiome and, potentially, host health.     

微生态调节剂在肿瘤治疗中的应用

肿瘤的治疗方法包括手术治疗、化学治疗、放射治疗、靶向治疗、免疫治疗等。但是药物副反应、疾病耐药和肿瘤复发是目前面临的困难。近年来,微生物与肿瘤相互作用的研究成为热点。越来越多的研究表明,可以通过调节微生态来对抗肿瘤,提高肿瘤治疗的疗效,减小治疗的副作用,从而进一步提高肿瘤患者的生活质量。本文就微生态调节剂应用于治疗肿瘤作一综述,我们回顾了有关益生菌在肿瘤治疗中的应用,此外,我们讨论益生菌、益生元、合生元、微生物代谢物和抗生素与化疗及免疫治疗共同应用的益处。     

The role of the microbiome in the neurobiology of social behaviour

Microbes colonise all multicellular life, and the gut microbiome has been shown to influence a range of host physiological and behavioural phenotypes. One of the most intriguing and least understood of these influences lies in the domain of the microbiome's interactions with host social behaviour, with new evidence revealing that the gut microbiome makes important contributions to animal sociality. However, little is known about the biological processes through which the microbiome might influence host social behaviour. Here, we synthesise evidence of the gut microbiome's interactions with various aspects of host sociality, including sociability, social cognition, social stress, and autism. We discuss evidence of microbial associations with the most likely physiological mediators of animal social interaction. These include the structure and function of regions of the ‘social' brain (the amygdala, the prefrontal cortex, and the hippocampus) and the regulation of ‘social’ signalling molecules (glucocorticoids including corticosterone and cortisol, sex hormones including testosterone, oestrogens, and progestogens, neuropeptide hormones such as oxytocin and arginine vasopressin, and monoamine neurotransmitters such as serotonin and dopamine). We also discuss microbiome‐associated host genetic and epigenetic processes relevant to social behaviour. We then review research on microbial interactions with olfaction in insects and mammals, which contribute to social signalling and communication. Following these discussions, we examine evidence of microbial associations with emotion and social behaviour in humans, focussing on psychobiotic studies, microbe–depression correlations, early human development, autism, and issues of statistical power, replication, and causality. We analyse how the putative physiological mediators of the microbiome–sociality connection may be investigated, and discuss issues relating to the interpretation of results. We also suggest that other candidate molecules should be studied, insofar as they exert effects on social behaviour and are known to interact with the microbiome. Finally, we consider different models of the sequence of microbial effects on host physiological development, and how these may contribute to host social behaviour.     

Primate microbiomes over time: Longitudinal answers to standing questions in microbiome research

To date, most insights into the processes shaping vertebrate gut microbiomes have emerged from studies with cross‐sectional designs. While this approach has been valuable, emerging time series analyses on vertebrate gut microbiomes show that gut microbial composition can change rapidly from 1 day to the next, with consequences for host physical functioning, health, and fitness. Hence, the next frontier of microbiome research will require longitudinal perspectives. Here we argue that primatologists, with their traditional focus on tracking the lives of individual animals and familiarity with longitudinal fecal sampling, are well positioned to conduct research at the forefront of gut microbiome dynamics. We begin by reviewing some of the most important ecological processes governing microbiome change over time, and briefly summarizing statistical challenges and approaches to microbiome time series analysis. We then introduce five questions of general interest to microbiome science where we think field‐based primate studies are especially well positioned to fill major gaps: (a) Do early life events shape gut microbiome composition in adulthood? (b) Do shifting social landscapes cause gut microbial change? (c) Are gut microbiome phenotypes heritable across variable environments? (d) Does the gut microbiome show signs of host aging? And (e) do gut microbiome composition and dynamics predict host health and fitness? For all of these questions, we highlight areas where primatologists are uniquely positioned to make substantial contributions. We review preliminary evidence, discuss possible study designs, and suggest future directions.     

Early sexual dimorphism in the developing gut microbiome of northern elephant seals

The gut microbiome is an integral part of a species' ecology, but we know little about how host characteristics impact its development in wild populations. Here, we explored the role of such intrinsic factors in shaping the gut microbiome of northern elephant seals (Mirounga angustirostris) during a critical developmental window of 6 weeks after weaning, when the pups stay ashore without feeding. We found substantial sex differences in the early‐life gut microbiome, even though males and females could not yet be distinguished morphologically. Sex and age both explained around 15% of the variation in gut microbial beta diversity, while microbial communities sampled from the same individual showed high levels of similarity across time, explaining another 40% of the variation. Only a small proportion of the variation in beta diversity was explained by health status, assessed by full blood counts, but clinically healthy individuals had a greater microbial alpha diversity than their clinically abnormal peers. Across the post‐weaning period, the northern elephant seal gut microbiome was highly dynamic. We found evidence for several colonization and extinction events as well as a decline in Bacteroides and an increase in Prevotella, a pattern that has previously been associated with the transition from nursing to solid food. Lastly, we show that genetic relatedness was correlated with gut microbiome similarity in males but not females, again reflecting early sex differences. Our study represents a naturally diet‐controlled and longitudinal investigation of how intrinsic factors shape the early gut microbiome in a species with extreme sex differences in morphology and life history.     

Roles of Probiotic Lactobacilli Inclusion in Helping Piglets Establish Healthy Intestinal Inter-environment for Pathogen Defense

The gastrointestinal tract of pigs is densely populated with microorganisms that closely interact with the host and with ingested feed. Gut microbiota benefits the host by providing nutrients from dietary substrates and modulating the development and function of the digestive and immune systems. An optimized gastrointestinal microbiome is crucial for pigs’ health, and establishment of the microbiome in piglets is especially important for growth and disease resistance. However, the microbiome in the gastrointestinal tract of piglets is immature and easily influenced by the environment. Supplementing the microbiome of piglets with probiotic bacteria such as Lactobacillus could help create an optimized microbiome by improving the abundance and number of lactobacilli and other indigenous probiotic bacteria. Dominant indigenous probiotic bacteria could improve piglets’ growth and immunity through certain cascade signal transduction pathways. The piglet body provides a permissive habitat and nutrients for bacterial colonization and growth. In return, probiotic bacteria produce prebiotics such as short-chain fatty acids and bacteriocins that benefit piglets by enhancing their growth and reducing their risk of enteric infection by pathogens. A comprehensive understanding of the interactions between piglets and members of their gut microbiota will help develop new dietary interventions that can enhance piglets’ growth, protect piglets from enteric diseases caused by pathogenic bacteria, and maximize host feed utilization.