Ex-germfree mice harboring intestinal microbiota derived from other animal species as an experimental model for ecology and metabolism of intestinal bacteria.

Ex-germfree (GF) animals harboring intestinal microbiota derived from other animal species, e.g. human-flora-associated (HFA) and pig-flora-associated (PFA) mice, have been considered as a tool for studying the ecology and metabolism of intestinal bacteria of man and animals. Human fecal microbiota was transferred into the intestines of the mice with minor modification by inoculating GF mice with human fecal suspensions. Interestingly, bifidobacteria were eliminated from some of the HFA mouse groups, whereas other dominant bacterial groups remained constant. Elimination of bifidobacteria appeared to be dependent on the composition of microbiota in the inoculated sample. Human fecal microbiota established in the intestines of the HFA mice reproduced in the intestine of offspring of these HFA mice and of cage-mated ex-GF mice without any remarkable change in composition. Although the HFA mice could be used for studying the effects of diet on human intestinal microbiota, the metabolism of microbiota of HFA mice reflected that of human feces with respect to some metabolic activities but not others. PFA mice were also a good model for studying the ecosystem of pig fecal microbiota and the control of short chain fatty acids in pig intestines, but not for studying putrefactive products generated in pig intestines. In conclusion, HFA and PFA mice provide a stable and valuable tool for studying the ecosystem and metabolism of the human and animal intestinal microbiota, but they have some limitations as a model.     

Development of intestinal microbiota in mice and its possible interaction with the evolution of luminal IgA in the intestine.

The development of the intestinal microbiota and the evolution of the fecal IgA in mice were analyzed from 18 to 40 days old by PCR temperature gradient gel electrophoresis (TGGE) and ELISA, respectively. There were two events for the diversification of the intestinal microbiota from suckling to maturity. The first change occurred between days 21 and 22 after birth, when the diversity of the intestinal microbiota showed a remarkable increase at this time. The second change occurred from days 27 to 30 after birth, and the increase in the diversity of the intestinal microbiota ceased. The amount of fecal IgA decreased from days 18 to 20, remained low until day 22, on day 23, it recovered and then continued to increase. This study suggests that there are possible interactions between the development of intestinal microbiota and the evolution of intestinal secretion of IgA in mice, the same as in rats, although the second change in mice intestinal microbiota occurred a few days later than in rats. The decline in maternal IgA supply as the suckling period proceeded presumably allowed the bacterial colonization. As a consequence of this increase in bacterial colonization, the secretion of the self-SIgA was accelerated in the pups.     

The Gut Microbiota of Wild Mice

The gut microbiota profoundly affects the biology of its host. The composition of the microbiota is dynamic and is affected by both host genetic and many environmental effects. The gut microbiota of laboratory mice has been studied extensively, which has uncovered many of the effects that the microbiota can have. This work has also shown that the environments of different research institutions can affect the mouse microbiota. There has been relatively limited study of the microbiota of wild mice, but this has shown that it typically differs from that of laboratory mice (and that maintaining wild caught mice in the laboratory can quite quickly alter the microbiota). There is also inter-individual variation in the microbiota of wild mice, with this principally explained by geographical location. In this study we have characterised the gut (both the caecum and rectum) microbiota of wild caught Mus musculus domesticus at three UK sites and have investigated how the microbiota varies depending on host location and host characteristics. We find that the microbiota of these mice are generally consistent with those described from other wild mice. The rectal and caecal microbiotas of individual mice are generally more similar to each other, than they are to the microbiota of other individuals. We found significant differences in the diversity of the microbiotas among mice from different sample sites. There were significant correlations of microbiota diversity and body weight, a measure of age, body-mass index, serum concentration of leptin, and virus, nematode and mite infection.     

羊水菌群的研究进展

传统观念认为胎儿在宫内发育的过程是无菌的。随着研究方法的快速发展,针对于微生物的研究方法从传统的培养到现代分子生物学检测的进步,研究者已经认识到胎盘、羊水中具有微生物的存在。目前的研究尚不能明确胎儿宫内胎盘、羊水的菌群来源及菌群转移的具体途径,但已有的研究提示羊水菌群最可能来源为母亲肠道、生殖道以及口腔。本文综述了研究者对羊水菌群认识的转变、羊水菌群的来源以及羊水菌群与早产的相关性。     

Gut microbiota in patients after surgical treatment for colorectal cancer

Colorectal cancer (CRC) is a common disease worldwide that is strongly associated with the gut microbiota. However, little is known regarding the gut microbiota after surgical treatment. 16S rRNA gene sequencing was used to evaluate differences in gut microbiota among colorectal adenoma patients, CRC patients, CRC postoperative patients and healthy controls by comparing gut microbiota diversity, overall composition and taxonomic signature abundance. The gut microbiota of CRC patients, adenoma patients and healthy controls developed in accordance with the adenoma-carcinoma sequence, with impressive shifts in the gut microbiota before or during the development of CRC. The gut microbiota of postoperative patients and CRC patients differed significantly. Subdividing CRC postoperative patients according to the presence or absence of newly developed adenoma which based on the colonoscopy findings revealed that the gut microbiota of newly developed adenoma patients differed significantly from that of clean intestine patients and was more similar to the gut microbiota of carcinoma patients than to the gut microbiota of healthy controls. The alterations of the gut microbiota between the two groups of postoperative patients corresponded to CRC prognosis. More importantly, we used the different gut microbiota as biomarkers to distinguish postoperative patients with or without newly developed adenoma, achieving an AUC value of 0.72. These insights on the changes in the gut microbiota of CRC patients after surgical treatment may allow the use of the microbiota as non-invasive biomarkers for the diagnosis of newly developed adenomas and to help prevent cancer recurrence in postoperative patients.     

The Effects and Mechanisms of Flavonoids on Cancer Prevention and Therapy: Focus on Gut Microbiota

Flavonoids are a group of polyphenolic compounds which are ubiquitously found in plants and are consumed as part of the human diet in substantial amounts. The verification of flavonoids'' cancer chemopreventive benefits has led to a significant interest in this field. Gut microbiota includes a diverse community of microorganisms and has a close relationship with cancer development. Increasing evidence has indicated that flavonoids exert anticarcinogenic effects by reshaping gut microbiota. Gut microbiota can convert flavonoids into bioactive metabolites that possess anticancer activity. Here, we present a brief introduction to gut microbiota and provide an overview of the interplay between gut microbiota and cancer pathogenesis. We also highlight the crucial roles of flavonoids in preventing cancer based on their regulation of gut microbiota. This review would encourage research on the flavonoid-intestinal microbiota interactions and clinical trials to validate the chemotherapeutic potentials of targeting gut microbiota by dietary bioactive compounds.     

How does plant sex alter microbiota assembly in dioecious plants?

Plant microbiota can greatly impact plant growth, defense, and health in different environments. Thus, it might be evolutionarily beneficial for plants to be able to control processes related to microbiota assembly. Dioecious plant species display sexual dimorphism in morphology, physiology, and immunity. These differences imply that male and female individuals might differently regulate their microbiota, but the role of sex in microbiota assembly has been largely neglected so far. Here, we introduce the mechanism of how sex controls microbiota in plants analogically to the sex regulation of gut microbiota in animals, in particular in humans. We argue that plant sex imposes selective pressure on filtering and constructing microbiota in the rhizosphere, phyllosphere, and endosphere along the soil–plant continuum. Since male plants are more resistant than female plants to environmental stresses, we suggest that a male host forms more stable and resistant plant microbiota that cooperate more effectively with the host to resist stresses. Male and female plants can distinguish whether a plant is of the same or different sex, and males can alleviate stress-caused damage in females. The impact of a male host on microbiota would protect female plants from unfavorable environments.     

肠道微生物群在人类健康衰老中的作用机制研究进展北大核心

衰老的特征是组织器官的功能衰退以及衰老相关疾病风险的增加,这给维护和促进健康长寿带来一系列新的挑战。尽管进行了广泛的衰老相关研究,但进展有限。人们越来越意识到肠道微生物群的结构和功能积极参与了衰老过程。肠道微生物群紊乱表现为许多与年龄相关的肠外器官轴的衰老。肠道微生物群可以被调节,这暗示了通过肠道微生物群抗衰老是一个可以实现的重要目标。本综述总结了肠道微生物群在不同年龄段中的动态演替,这种动态的肠道微生物群从胎儿到出生和婴儿期开始迅速发展,从断奶期到幼儿期迅速变化,然后建立稳定的成年人菌群,直到随着年龄增长最后发生衰退;肠道微生物群与肠外器官轴(大脑、心脏、肝脏、胰腺、肌肉、皮肤和骨骼)衰老相关疾病,以及通过饮食、粪菌移植和微生态制剂调节肠道微生物群靶向抗衰老的研究进展,以期为调控肠道微生物群抗衰老研究提供参考。     

肠道菌群与心血管疾病关系研究进展

近年来,越来越多的研究表明肠道菌群在心血管疾病、2型糖尿病、肥胖等疾病的发病过程中起着主要作用,肠道菌群组成改变以及肠道菌群代谢物水平改变是导致疾病发生发展的重要因素,人们对肠道菌群与宿主之间的相互作用产生极大兴趣。本文系统总结了肠道菌群组成结构改变及肠道菌群代谢物改变与动脉粥样硬化、高血压、心肌梗死、心力衰竭等心血管疾病的相关性,阐明了肠道菌群可能是促进心血管疾病发病的原因之一。因此,通过改变饮食结构和使用抗生素、益生菌制剂及肠道菌群代谢物氧化三甲胺(TMAO)小分子抑制剂,来调控肠道菌群组成及代谢物水平有望作为心血管疾病治疗的新靶点。     

肠道微生物对肥胖影响

肠道微生物是哺乳动物最密集的微生物群落,也是最多样化的微生物群落之一。随着宏基因组学的不断发展,肠道微生物成为热门的研究领域。肠道微生物具有保护和代谢等功能,在胰岛素抵抗和肥胖等疾病中发挥重要作用。本文介绍了肠道微生物及其代谢物通过调节食欲、神经递质合成分泌、炎性反应进而调节肥胖,探讨了肠道微生物的影响因素,展望了肠道微生物对治疗人类肥胖的应用前景。     

Carbon metabolism of the cryptoendolithic microbiota from the Antarctic desert.

The carbon metabolism of the cryptoendolithic microbiota of sandstones from the Ross Desert of Antarctica was studied in situ and in vitro. Organic and inorganic carbon compounds were metabolized by the microbiota, with bicarbonate incorporation into community lipids occurring primarily in the light. Light intensity affected the photometabolism of carbon with a photosynthesis-intensity response optimum at about 200 to 300 micromoles of photons per m2 per s. Photosynthesis was also affected by temperature, with a minimum activity at -5 degrees C, an optimum activity at 15 degrees C, and complete inhibition at 35 degrees C, indicating that the cryptoendolithic community was psychrophilic. The primary source of CO2 for photosynthesis in situ was the atmosphere. CO2 may also be photometabolized by using the carbon produced from respiration within the endolithic community. Photosynthesis occurred maximally when the microbiota was wet with liquid water and to a lesser extent in a humid atmosphere. This simple microbial community, therefore, exists under extremes of water, light, and temperature stress which affect and control its metabolism.     

肠道微生态与白血病的研究进展

微生物群与人体的健康密切相关,约20%的恶性肿瘤与微生态失调有关。研究显示肠道微生物可以调节造血,其与血液系统疾病的关系逐渐得到研究者的关注,肠道微生物参与白血病的发生发展,影响白血病的治疗效果。较早的暴露于微生物群是儿童白血病的保护性因素,化疗会引起肠道微生物紊乱,肠道微生物可以改变化疗药物的疗效和毒性,其多样性和组成能够预测化疗相关的并发症,通过微生态制剂和粪菌移植可以减少化疗相关的并发症。本文从肠道微生态与白血病及其并发症的关系,以及调节肠道微生态对白血病的影响两个方面的最新进展进行综述。     

Composition and temporal stability of the gut microbiota in older persons

The composition and function of the human gut microbiota has been linked to health and disease. We previously identified correlations between habitual diet, microbiota composition gradients and health gradients in an unstratified cohort of 178 elderly subjects. To refine our understanding of diet–microbiota associations and differential taxon abundance, we adapted an iterative bi-clustering algorithm (iterative binary bclustering of gene sets (iBBiG)) and applied it to microbiota composition data from 732 faecal samples from 371 ELDERMET cohort subjects, including longitudinal samples. We thus identified distinctive microbiota configurations associated with ageing in both community and long-stay residential care elderly subjects. Mixed-taxa populations were identified that had clinically distinct associations. Microbiota temporal instability was observed in both community-dwelling and long-term care subjects, particularly in those with low initial microbiota diversity. However, the stability of the microbiota of subjects had little impact on the directional change of the microbiota as observed for long-stay subjects who display a gradual shift away from their initial microbiota. This was not observed in community-dwelling subjects. This directional change was associated with duration in long-stay. Changes in these bacterial populations represent the loss of the health-associated and youth-associated microbiota components and gain of an elderly associated microbiota. Interestingly, community-associated microbiota configurations were impacted more by the use of antibiotics than the microbiota of individuals in long-term care, as the community-associated microbiota showed more loss but also more recovery following antibiotic treatment. This improved definition of gut microbiota composition patterns in the elderly will better inform the design of dietary or antibiotic interventions targeting the gut microbiota.     

Root microbiota shift in rice correlates with resident time in the field and developmental stage

Land plants in natural soil form intimate relationships with the diverse root bacterial microbiota. A growing body of evidence shows that these microbes are important for plant growth and health. Root microbiota composition has been widely studied in several model plants and crops; however, little is known about how root microbiota vary throughout the plant's life cycle under field conditions. We performed longitudinal dense sampling in field trials to track the time-series shift of the root microbiota from two representative rice cultivars in two separate locations in China. We found that the rice root microbiota varied dramatically during the vegetative stages and stabilized from the beginning of the reproductive stage, after which the root microbiota underwent relatively minor changes until rice ripening. Notably, both rice genotype and geographical location influenced the patterns of root microbiota shift that occurred during plant growth. The relative abundance of Deltaproteobacteria in roots significantly increased overtime throughout the entire life cycle of rice, while that of Betaproteobacteria, Firmicutes, and Gammaproteobacteria decreased. By a machine learning approach, we identified biomarker taxa and established a model to correlate root microbiota with rice resident time in the field(e.g., Nitrospira accumulated from 5 weeks/tillering in field-grown rice). Our work provides insights into the process of rice root microbiota establishment.     

Motility allows S. Typhimurium to benefit from the mucosal defence

The mammalian intestine is colonized by a dense bacterial community, called microbiota. The microbiota shields from intestinal infection (colonization resistance). Recently, we have shown that enteropathogenic Salmonella spp. can exploit inflammation to compete with the intestinal microbiota. The mechanisms explaining the enhanced pathogen growth in the inflamed intestine are elusive. Here, we analysed the function of bacterial flagella in the inflamed intestine using a mouse model for acute Salmonella Typhimurium enterocolitis. Mutations affecting flagellar assembly (Fla^-) and chemotaxis (Che^-) impaired the pathogen's fitness in the inflamed intestine, but not in the normal gut. This was attributable to a localized source of high-energy nutrients (e.g. galactose-containing glyco-conjugates, mucin) released as an element of the mucosal defence. Motility allows Salmonella Typhimurium to benefit from these nutrients and utilize them for enhanced growth. Thus, nutrient availability contributes to enhanced pathogen growth in the inflamed intestine. Strategies interfering with bacterial motility or nutrient availability might offer starting points for therapeutic approaches.     

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     

Meta‐Omics‐ and Metabolic Modeling‐Assisted Deciphering of Human Microbiota Metabolism

The human microbiota is a complex community of commensal, symbiotic, and pathogenic microbes that play a crucial role in maintaining the homeostasis of human health. Such a homeostasis is maintained through the collective functioning of enzymatic genes responsible for the production of metabolites, enabling the interaction and signaling within microbiota as well as between microbes and the human host. Understanding microbial genes, their associated chemistries and functions would be valuable for engineering systemic metabolic pathways within the microbiota to manage human health and diseases. Given that there are many unknown gene metabolic functions and interactions, increasing efforts have been made to gain insights into the underlying functions of microbiota metabolism. This can be achieved through culture‐independent metagenomic approaches and metabolic modeling to simulate the microenvironment of human microbiota. In this article, the recent advances in metagenome mining and functional profiling for the discovery of the genetic and biochemical links in human microbiota metabolism as well as metabolic modeling for simulation and prediction of metabolic fluxes in the human microbiota are reviewed. This review provides useful insights into the understanding, reconstruction, and modulation of the human microbiota guided by the knowledge acquired from the basic understanding of the human microbiota metabolism.     

宿主遗传因素对肠道菌群的影响

随着高通量测序技术的发展,人们逐渐认识到肠道菌群与人类的健康和疾病密切相关,并发现肠道菌群受很多因素的影响。除了研究传统饮食和药物对肠道菌群的改变外,近年来,科学家也开始注重遗传因素在塑造肠道菌群中的作用。遗传因素可决定宿主的饮食偏好、肠道的生理结构、肠道屏障功能和免疫功能等,而这些都直接与肠道菌群相互作用,参与肠道微生态平衡的构建和稳定。因此,在研究肠道菌群与疾病发生相关性的过程中也需要考虑遗传因素的重要性。随着基因敲除、无菌小鼠和菌群移植等实验技术的革新,以及主成分分析、数量性状基因座和全基因组关联性分析等大数据分析手段的提高,科学家能够深入研究宿主遗传基因与肠道菌群之间的关联性,从而证明宿主遗传基因在塑造肠道微生态的过程中具有重要作用。本文将首先简述肠道菌群与疾病发生之间可能存在的联系,然后从多方面综述遗传因素对肠道菌群的影响及主要的研究进展,从而为今后该领域的深入研究提供重要的指导,也为今后预防和治疗疾病提供新思路和新方法。     

Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer

Recent reports have suggested the involvement of gut microbiota in the progression of colorectal cancer (CRC). We utilized pyrosequencing based analysis of 16S rRNA genes to determine the overall structure of microbiota in patients with colorectal cancer and healthy controls; we investigated microbiota of the intestinal lumen, the cancerous tissue and matched noncancerous normal tissue. Moreover, we investigated the mucosa-adherent microbial composition using rectal swab samples because the structure of the tissue-adherent bacterial community is potentially altered following bowel cleansing. Our findings indicated that the microbial structure of the intestinal lumen and cancerous tissue differed significantly. Phylotypes that enhance energy harvest from diets or perform metabolic exchange with the host were more abundant in the lumen. There were more abundant Firmicutes and less abundant Bacteroidetes and Proteobacteria in lumen. The overall microbial structures of cancerous tissue and noncancerous tissue were similar; however the tumor microbiota exhibited lower diversity. The structures of the intestinal lumen microbiota and mucosa-adherent microbiota were different in CRC patients compared to matched microbiota in healthy individuals. Lactobacillales was enriched in cancerous tissue, whereas Faecalibacterium was reduced. In the mucosa-adherent microbiota, Bifidobacterium, Faecalibacterium, and Blautia were reduced in CRC patients, whereas Fusobacterium, Porphyromonas, Peptostreptococcus, and Mogibacterium were enriched. In the lumen, predominant phylotypes related to metabolic disorders or metabolic exchange with the host, Erysipelotrichaceae, Prevotellaceae, and Coriobacteriaceae were increased in cancer patients. Coupled with previous reports, these results suggest that the intestinal microbiota is associated with CRC risk and that intestinal lumen microflora potentially influence CRC risk via cometabolism or metabolic exchange with the host. However, mucosa-associated microbiota potentially affects CRC risk primarily through direct interaction with the host.