阴道微生物组：种群特征与疾病干预治疗

高通量测序技术的发展显著加快了对人类微生物组的理解。将人体微生物组与疾病关联,力求阐明疾病的发生进程,是推进个性化精准医疗的重要研究方向。近年来,栖居于女性阴道的微生物菌群日益受到关注,发现其生态失调与疾病发生、演变密不可分。文中综述了阴道微生物组与生殖道疾病发生、进展和治疗的最新进展,同时对阴道微生物组培养组、益生菌工程化改造以及合成菌群在阴道微生物组学研究以及疾病干预与治疗方面的前景进行了展望。     

Intestinal microbiota in human health and disease: the impact of probiotics

The complex communities of microorganisms that colonise the human gastrointestinal tract play an important role in human health. The development of culture-independent molecular techniques has provided new insights in the composition and diversity of the intestinal microbiota. Here, we summarise the present state of the art on the intestinal microbiota with specific attention for the application of high-throughput functional microbiomic approaches to determine the contribution of the intestinal microbiota to human health. Moreover, we review the association between dysbiosis of the microbiota and both intestinal and extra-intestinal diseases. Finally, we discuss the potential of probiotic microorganism to modulate the intestinal microbiota and thereby contribute to health and well-being. The effects of probiotic consumption on the intestinal microbiota are addressed, as well as the development of tailor-made probiotics designed for specific aberrations that are associated with microbial dysbiosis.     

Dysbiotic drift and biopsychosocial medicine: how the microbiome links personal,public and planetary health

The emerging concept of planetary health emphasizes that the health of human civilization is intricately connected to the health of natural systems within the Earth’s biosphere; here, we focus on the rapidly progressing microbiome science - the microbiota-mental health research in particular - as a way to illustrate the pathways by which exposure to biodiversity supports health. Microbiome science is illuminating the ways in which stress, socioeconomic disadvantage and social polices interact with lifestyle and behaviour to influence the micro and macro-level biodiversity that otherwise mediates health. Although the unfolding microbiome and mental health research is dominated by optimism in biomedical solutions (e.g. probiotics, prebiotics), we focus on the upstream psychosocial and ecological factors implicated in dysbiosis; we connect grand scale biodiversity in the external environment with differences in human-associated microbiota, and, by extension, differences in immune function and mental outlook. We argue that the success of planetary health as a new concept will be strengthened by a more sophisticated understanding of the ways in which individuals develop emotional connections to nature (nature relatedness) and the social policies and practices which facilitate or inhibit the pro-environmental values that otherwise support personal, public and planetary health.     

Investigating the biological and clinical significance of human dysbioses

Culture-independent microbiological technologies that interrogate complex microbial populations without prior axenic culture, coupled with high-throughput DNA sequencing, have revolutionized the scale, speed and economics of microbial ecological studies. Their application to the medical realm has led to a highly productive merger of clinical, experimental and environmental microbiology. The functional roles played by members of the human microbiota are being actively explored through experimental manipulation of animal model systems and studies of human populations. In concert, these studies have appreciably expanded our understanding of the composition and dynamics of human-associated microbial communities (microbiota). Of note, several human diseases have been linked to alterations in the composition of resident microbial communities, so-called dysbiosis. However, how changes in microbial communities contribute to disease etiology remains poorly defined. Correlation of microbial composition represents integration of only two datasets (phenotype and microbial composition). This article explores strategies for merging the human microbiome data with multiple additional datasets (e.g. host single nucleotide polymorphisms and host gene expression) and for integrating patient-based data with results from experimental animal models to gain deeper understanding of how host-microbe interactions impact disease.     

Targeting friend and foe: Emerging therapeutics in the age of gut microbiome and disease

Mucosal surfaces that line our gastrointestinal tract are continuously exposed to trillions of bacteria that form a symbiotic relationship and impact host health and disease. It is only beginning to be understood that the cross-talk between the host and microbiome involve dynamic changes in commensal bacterial population, secretion, and absorption of metabolites between the host and microbiome. As emerging evidence implicates dysbiosis of gut microbiota in the pathology and progression of various diseases such as inflammatory bowel disease, obesity, and allergy, conventional treatments that either overlook the microbiome in the mechanism of action, or eliminate vast populations of microbes via wide-spectrum antibiotics need to be reconsidered. It is also becoming clear the microbiome can influence the body’s response to therapeutic treatments for cancers. As such, targeting the microbiome as treatment has garnered much recent attention and excitement from numerous research labs and biotechnology companies. Treatments range from fecal microbial transplantation to precision-guided molecular approaches. Here, we survey recent progress in the development of innovative therapeutics that target the microbiome to treat disease, and highlight key findings in the interplay between host microbes and therapy.     

Dysbiotic drift: mental health,environmental grey space,and microbiota

Advances in research concerning the mental health implications of dietary patterns and select nutrients have been remarkable. At the same time, there have been rapid increases in the understanding of the ways in which non-pathogenic microbes can potentially influence many aspects of human health, including those in the mental realm. Discussions of nutrition and microbiota are often overlapping. A separate, yet equally connected, avenue of research is that related to natural (for example, green space) and built environments, and in particular, how they are connected to human cognition and behaviors. It is argued here that in Western industrial nations a ‘disparity of microbiota’ might be expected among the socioeconomically disadvantaged, those whom face more profound environmental forces. Many of the environmental forces pushing against the vulnerable are at the neighborhood level. Matching the developing microbiome research with existing environmental justice research suggests that grey space may promote dysbiosis by default. In addition, the influence of Westernized lifestyle patterns, and the marketing forces that drive unhealthy behaviors in deprived communities, might allow dysbiosis to be the norm rather than the exception in those already at high risk of depression, subthreshold (subsyndromal) conditions, and subpar mental health. If microbiota are indeed at the intersection of nutrition, environmental health, and lifestyle medicine (as these avenues pertain to mental health), then perhaps the rapidly evolving gut-brain-microbiota conversation needs to operate through a wider lens. In contrast to the more narrowly defined psychobiotic, the term eco-psychotropic is introduced.     

Global amphibian declines: sorting the hypotheses

Abstract. Reports of malformed amphibians and global amphibian declines have led to public concern, particularly because amphibians are thought to be indicator species of overall environmental health. The topic also draws scientific attention because there is no obvious, simple answer to the question of what is causing amphibian declines? Complex interactions of several anthropogenic factors are probably at work, and understanding amphibian declines may thus serve as a model for understanding species declines in general. While we have fewer answers than we would like, there are six leading hypotheses that we sort into two classes. For class I hypotheses, alien species, over‐exploitation and land use change, we have a good understanding of the ecological mechanisms underlying declines; these causes have affected amphibian populations negatively for more than a century. However, the question remains as to whether the magnitude of these negative effects increased in the 1980s, as scientists began to notice a global decline of amphibians. Further, remedies for these problems are not simple. For class II hypotheses, global change (including UV radiation and global climate change), contaminants and emerging infectious diseases we have a poor, but improving understanding of how each might cause declines. Class II factors involve complex and subtle mechanistic underpinnings, with probable interactions among multiple ecological and evolutionary variables. They may also interact with class I hypotheses. Suspected mechanisms associated with class II hypotheses are relatively recent, dating from at least the middle of the 20th century. Did these causes act independently or in concert with pre‐existing negative forces of class I hypotheses to increase the rate of amphibian declines to a level that drew global attention? We need more studies that connect the suspected mechanisms underlying both classes of hypotheses with quantitative changes in amphibian population sizes and species numbers. An important step forward in this task is clarifying the hypotheses and conditions under which the various causes operate alone or together.     

Two amphibian diseases, chytridiomycosis and ranaviral disease, are now globally notifiable to the World Organization for Animal Health (OIE): an assessment

The global trade in amphibians entails the transport of tens of millions of live animals each year. In addition to the impact harvesting wild animals can have on amphibian populations, there is mounting evidence that the emerging pathogens Batrachochytrium dendrobatidis and ranaviruses, the aetiological agents of chytridiomycosis and ranaviral disease, respectively, are spread through this trade. The link between these pathogens and amphibian declines and extinctions suggests that the epidemiological impact of the trade is significant and may negatively affect conservation and trade economics. Here we present a brief assessment of the volume of the global trade in live amphibians, the risk of individuals harboring infection, and information on the recent listing by the World Organization for Animal Health (OIE) of chytridiomycosis and ranaviral disease in the OIE Aquatic Animal Health Code. This listing made chytridiomycosis and ranaviral disease internationally notifiable diseases and thus subject to OIE standards, which aim to assure the sanitary safety of international trade in live amphibians and their products.     

Beyond microbial community composition: functional activities of the oral microbiome in health and disease

The oral microbiome plays a relevant role in the health status of the host and is a key element in a variety of oral and non-oral diseases. Despite advances in our knowledge of changes in microbial composition associated with different health conditions the functional aspects of the oral microbiome that lead to dysbiosis remain for the most part unknown. In this review, we discuss the progress made towards understanding the functional role of the oral microbiome in health and disease and how novel technologies are expanding our knowledge on this subject.     

The amphibian microbiome exhibits poor resilience following pathogen-induced disturbance

Infectious pathogens can disrupt the microbiome in addition to directly affecting the host. Impacts of disease may be dependent on the ability of the microbiome to recover from such disturbance, yet remarkably little is known about microbiome recovery after disease, particularly in nonhuman animals. We assessed the resilience of the amphibian skin microbial community after disturbance by the pathogen, Batrachochytrium dendrobatidis (Bd). Skin microbial communities of laboratory-reared mountain yellow-legged frogs were tracked through three experimental phases: prior to Bd infection, after Bd infection (disturbance), and after clearing Bd infection (recovery period). Bd infection disturbed microbiome composition and altered the relative abundances of several dominant bacterial taxa. After Bd infection, frogs were treated with an antifungal drug that cleared Bd infection, but this did not lead to recovery of microbiome composition (measured as Unifrac distance) or relative abundances of dominant bacterial groups. These results indicate that Bd infection can lead to an alternate stable state in the microbiome of sensitive amphibians, or that microbiome recovery is extremely slow—in either case resilience is low. Furthermore, antifungal treatment and clearance of Bd infection had the additional effect of reducing microbial community variability, which we hypothesize results from similarity across frogs in the taxa that colonize community vacancies resulting from the removal of Bd. Our results indicate that the skin microbiota of mountain yellow-legged frogs has low resilience following Bd-induced disturbance and is further altered by the process of clearing Bd infection, which may have implications for the conservation of this endangered amphibian.Subject terms: Microbial ecology, Community ecology     

Immune and genetic gardening of the intestinal microbiome

The mucosal immune system – consisting of adaptive and innate immune cells as well as the epithelium – is profoundly influenced by its microbial environment. There is now growing evidence that the converse is also true, that the immune system shapes the composition of the intestinal microbiome. During conditions of health, this bidirectional interaction achieves a homeostasis in which inappropriate immune responses to non-pathogenic microbes are averted and immune activity suppresses blooms of potentially pathogenic microbes (pathobionts). Genetic alteration in immune/epithelial function can affect host gardening of the intestinal microbiome, contributing to the diversity of intestinal microbiota within a population and in some cases allowing for unfavorable microbial ecologies (dysbiosis) that confer disease susceptibility.     

Cervicovaginal microbiome dynamics after taking oral probiotics

The vaginal microbiota is less complex than the gut microbiota, and the colonization of Lactobacillus in the female vagina is considered to be critical for reproductive health. Oral probiotics have been suggested as promising means to modulate vaginal homeostasis in the general population. In this study, 60 Chinese women were followed for over a year before, during, and after treatment with the probiotics Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14. Shotgun metagenomic data of 1334 samples from multiple body sites did not support a colonization route of the probiotics from the oral cavity to the intestinal tract and then to the vagina. Our analyses enable the classification of the cervicovaginal microbiome into a stable state and a state of dysbiosis. The microbiome in the stable group steadily maintained a relatively high abundance of Lactobacilli over one year, which was not affected by probiotic intake, whereas in the dysbiosis group, the microbiota was more diverse and changed markedly over time. Data from a subset of the dysbiosis group suggests this subgroup possibly benefited from supplementation with the probiotics,indicating that probiotics supplementation can be prescribed for women in a subclinical microbiome setting of dysbiosis, providing opportunities for targeted and personalized microbiome reconstitution.     

Circadian Disorganization Alters Intestinal Microbiota

Intestinal dysbiosis and circadian rhythm disruption are associated with similar diseases including obesity, metabolic syndrome, and inflammatory bowel disease. Despite the overlap, the potential relationship between circadian disorganization and dysbiosis is unknown; thus, in the present study, a model of chronic circadian disruption was used to determine the impact on the intestinal microbiome. Male C57BL/6J mice underwent once weekly phase reversals of the light:dark cycle (i.e., circadian rhythm disrupted mice) to determine the impact of circadian rhythm disruption on the intestinal microbiome and were fed either standard chow or a high-fat, high-sugar diet to determine how diet influences circadian disruption-induced effects on the microbiome. Weekly phase reversals of the light:dark (LD) cycle did not alter the microbiome in mice fed standard chow; however, mice fed a high-fat, high-sugar diet in conjunction with phase shifts in the light:dark cycle had significantly altered microbiota. While it is yet to be established if some of the adverse effects associated with circadian disorganization in humans (e.g., shift workers, travelers moving across time zones, and in individuals with social jet lag) are mediated by dysbiosis, the current study demonstrates that circadian disorganization can impact the intestinal microbiota which may have implications for inflammatory diseases.     

On the origin of species: Factors shaping the establishment of infant's gut microbiota

The human gut microbiota is a complex and dynamic ecosystem, which naturally lives in a symbiotic relationship with the host. Perturbations of the microbial composition (dysbiosis) and reduced diversity may promote disease susceptibility and recurrence. In contrast to the mature intestinal microbiota of healthy adults, which appears relatively stable over time, the infant's microbiome only establishes and matures during the first years of life. In this respect, early childhood seems to represent a crucial age‐window in disease prevention, since microbial diversification and maturation of the microbiome primarily occurs during this period of life. A better understanding of ecological processes and pioneer consortia in microbial development is crucial, in order to support the development of a beneficial microbiota. Various deterministic and stochastic aspects seem to shape the microbiome in early life, including maternal, environmental, and host factors. Here, we review the current understanding of the origin of pioneer bacteria and the evolutionary factors that influence the development of the gut microbiota in infants. In addition, future perspectives, including manipulating and promoting the succession of initial bacteria during infancy, will be highlighted. Birth Defects Research (Part C) 105:240–251, 2015. © 2015 Wiley Periodicals, Inc.     

A comparison of understanding of the amphibian crisis by zoo visitors across three countries

Despite the global declines in the rate of amphibians, evaluation of public understanding of the crisis has not yet been carried out. We surveyed visitors (n = 1,293) at 15 zoos in Brazil, New Zealand, and the United Kingdom, using a certainty‐based assessment method to compare visitor knowledge of the global amphibian crisis. We further analyzed zoo educational material about amphibians to explore its potential to raise awareness through amphibian‐focused environmental education. Visitors in the three countries had relatively little understanding of amphibians and the global amphibian crisis. When the degree of confidence in answering the questions (high, medium, and low) is accounted for, correct answers varied between 28% and 39%. This compared to scores of between 58% and 73% when the degree of confidence in responding was not accounted for. However, specific areas of knowledge (e.g., biology, conservation, biogeography, and conceptual ideas) varied significantly across the countries. Visitors had a weaker grasp of biogeographical and conservation issues than general amphibian biology. Zoo visitors in Brazil knew less about amphibian conservation than those in New Zealand or the United Kingdom. There was less amphibian‐focused content in educational materials in zoos in Brazil than there was in the United Kingdom. Improving information about the global amphibian crisis may increase support for future conservation actions. Outreach education is one of the most important approaches in any strategic planning for conservation of species. Amphibian‐focused environmental education at institutions such as zoos and aquaria can be a crucial intervention to support amphibian conservation worldwide.     

The dynamic microbiome

While our genomes are essentially static, our microbiomes are inherently dynamic. The microbial communities we harbor in our bodies change throughout our lives due to many factors, including maturation during childhood, alterations in our diets, travel, illnesses, and medical treatments. Moreover, there is mounting evidence that our microbiomes change us, by promoting health through their beneficial actions or by increasing our susceptibility to diseases through a process termed dysbiosis. Recent technological advances are enabling unprecedentedly detailed studies of the dynamics of the microbiota in animal models and human populations. This review will highlight key areas of investigation in the field, including establishment of the microbiota during early childhood, temporal variability of the microbiome in healthy adults, responses of the microbiota to intentional perturbations such as antibiotics and dietary changes, and prospective analyses linking changes in the microbiota to host disease status. Given the importance of computational methods in the field, this review will also discuss issues and pitfalls in the analysis of microbiome time-series data, and explore several promising new directions for mathematical model and algorithm development.     

Conservation metagenomics: a new branch of conservation biology

Multifaceted approaches are required to monitor wildlife populations and improve conservation efforts. In the last decade,increasing evidence suggests that metagenomic analysis offers valuable perspectives and tools for identifying microbial communities and functions. It has become clear that gut microbiome plays a critical role in health, nutrition, and physiology of wildlife, including numerous endangered animals in the wild and in captivity. In this review, we first introduce the human microbiome and metagenomics, highlighting the importance of microbiome for host fitness. Then, for the first time, we propose the concept of conservation metagenomics, an emerging subdiscipline of conservation biology, which aims to understand the roles of the microbiota in evolution and conservation of endangered animals. We define what conservation metagenomics is along with current approaches, main scientific issues and significant implications in the study of host evolution, physiology,nutrition, ecology and conservation. We also discuss future research directions of conservation metagenomics. Although there is still a long way to go, conservation metagenomics has already shown a significant potential for improving the conservation and management of wildlife.