Microbiota In Human Health Research Articles

Gut microbiota and obesity.

The human intestine harbors a complex bacterial community called the gut microbiota. This microbiota is specific to each individual despite the existence of several bacterial species shared by the majority of adults. The influence of the gut microbiota in human health and disease has been revealed in the recent years. Particularly, the use of germ-free animals and microbiota transplant showed that the gut microbiota may play a causal role in the development of obesity and associated metabolic disorders, and lead to identification of several mechanisms. In humans, differences in microbiota composition, functional genes and metabolic activities are observed between obese and lean individuals suggesting a contribution of the gut microbiota to these phenotypes. Finally, the evidence linking gut bacteria to host metabolism could allow the development of new therapeutic strategies based on gut microbiota modulation to treat or prevent obesity.

Temporal and technical variability of human gut metagenomes.

BackgroundMetagenomics has become a prominent approach for exploring the role of the gut microbiota in human health. However, the temporal variability of the healthy gut microbiome has not yet been studied in depth using metagenomics and little is known about the effects of different sampling and preservation approaches. We performed metagenomic analysis on fecal samples from seven subjects collected over a period of up to two years to investigate temporal variability and assess preservation-induced variation, specifically, fresh frozen compared to RNALater. We also monitored short-term disturbances caused by antibiotic treatment and bowel cleansing in one subject.ResultsWe find that the human gut microbiome is temporally stable and highly personalized at both taxonomic and functional levels. Over multiple time points, samples from the same subject clustered together, even in the context of a large dataset of 888 European and American fecal metagenomes. One exception was observed in an antibiotic intervention case where, more than one year after the treatment, samples did not resemble the pre-treatment state. Clustering was not affected by the preservation method. No species differed significantly in abundance, and only 0.36% of gene families were differentially abundant between preservation methods.ConclusionsTechnical variability is small compared to the temporal variability of an unperturbed gut microbiome, which in turn is much smaller than the observed between-subject variability. Thus, short-term preservation of fecal samples in RNALater is an appropriate and cost-effective alternative to freezing of fecal samples for metagenomic studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0639-8) contains supplementary material, which is available to authorized users.

Implication of gut microbiota in human health.

Gut-microbiota (GM) is considered a hidden metabolic organ of the human body, providing biochemical pathways which are absent in the host. Balanced diet with calorie restriction (CR) promotes growth of healthy microbiota, leading to longevity by down-regulating inflammatory responses. While, dysbiosis leads to body dysfunction, inducing metabolic disorders, causing poor epithelial architecture, and impeding the development of mucosal-associated lymphoid tissue, resulting in with reduced T and B cell populations, rendering the body prone to infections, cancer and allergy. The GM enzymes activity is a new risk factor for cancer while gut-derived interleukin-6 is associated with hepatocellular carcinoma development. GM can also influence the brain biochemistry and emotional behavior. The altered GM affects the genes involved in second messenger pathway and long-term potentiation, leading to their differential expression in the hippocampus, cortex, striatum and cerebellum. In addition, the dysbiotic GM is associated with autistic disorder. Living with dysbiotic GM is possible with consequences of serious impairments.

The Interplay between the Microbiota and Enterohemorrhagic Escherichia coli

The gastrointestinal tract of mammals is home to a plethora of microbial species that comprise the microbiota. The role of the microbiota in human health is at the forefront of science in recent years, because it is now appreciated that this intricate microbe-host association shapes the host's immune response and physiology. Many diseases are associated with changes in the microbiota, called dysbiosis. Dysbiosis is associated with obesity, metabolic syndromes, inflammatory bowel-disease, inflammatory bowel syndrome, cancer, diabetes, allergies, and autism. The microbiota is largely regarded as a barrier to enteric infections, such as with enterohemorrhagic Escherichia coli (EHEC). However, the interactions between pathogens and the microbiota are largely unknown, as is how these interactions influence the outcome of enteric disease. The microbial composition of the gastrointestinal tract shapes the landscape in which EHEC survives within the host. This organism competes for nutrients derived from the host diet, liberates additional resources from dietary and host sources, and produces signaling molecules sensed by EHEC to direct gene expression. To successfully colonize the recto-anal junction of a ruminant, the EHEC reservoir, or the colon of a human, an accidental host, EHEC must alter its physiology to survive within the host digestive tract. In this article, we explore the classes of molecules produced or modified by the microbiota that appear to be instrumental in governing virulence gene expression of EHEC. We also explore how interaction with different microbiotas influences EHEC infectivity and host interaction.

Ingestible gastrointestinal sampling devices: state-of-the-art and future directions.

Despite the significant contribution of gastrointestinal diseases to the global disease burden and the increasing recognition of the role played by the intestinal microbiota in human health and disease states, conventional methods of exploring and collecting samples from the gastrointestinal tract remain invasive, resource intensive, and often unable to capture all the information contained in these heterogeneous samples. A new class of gastrointestinal sampling capsules is emerging in the literature, which contains the components required for an autonomous intra-luminal device and preserves the spatial and temporal information of the gastrointestinal samples. In this paper, we identify the primary design requirements for gastrointestinal sampling capsules, and we review the state-of-the-art for different components and functionalities. We also suggest two design concepts, and we highlight future directions for this class of biomedical devices.

The microbiome explored: recent insights and future challenges

One of the most exciting scientific advances in recent years has been the realization that commensal microorganisms are not simple 'passengers' in our bodies, but instead have key roles in our physiology, including our immune responses and metabolism, as well as in disease. These insights have been obtained, in part, through the work of large-scale, consortium-driven metagenomic projects. Here, five experts in the field of microbiome research discuss the most surprising and exciting new findings, and outline the future steps that will be necessary to elucidate the numerous roles of the microbiota in human health and disease and to develop viable therapeutic strategies.

Multivariate Approach for Studying Interactions between Environmental Variables and Microbial Communities

To understand the role of human microbiota in health and disease, we need to study effects of environmental and other epidemiological variables on the composition of microbial communities. The composition of a microbial community may depend on multiple factors simultaneously. Therefore we need multivariate methods for detecting, analyzing and visualizing the interactions between environmental variables and microbial communities. We provide two different approaches for multivariate analysis of these complex combined datasets: (i) We select variables that correlate with overall microbiota composition and microbiota members that correlate with the metadata using canonical correlation analysis, determine independency of the observed correlations in a multivariate regression analysis, and visualize the effect size and direction of the observed correlations using heatmaps; (ii) We select variables and microbiota members using univariate or bivariate regression analysis, followed by multivariate regression analysis, and visualize the effect size and direction of the observed correlations using heatmaps. We illustrate the results of both approaches using a dataset containing respiratory microbiota composition and accompanying metadata. The two different approaches provide slightly different results; with approach (i) using canonical correlation analysis to select determinants and microbiota members detecting fewer and stronger correlations only and approach (ii) using univariate or bivariate analyses to select determinants and microbiota members detecting a similar but broader pattern of correlations. The proposed approaches both detect and visualize independent correlations between multiple environmental variables and members of the microbial community. Depending on the size of the datasets and the hypothesis tested one can select the method of preference.

The PharmacoMicrobiomics Portal: A Database for Drug-Microbiome Interactions

The human microbiota directly and indirectly impacts drug pharmacokinetics and pharmacodynamics, thus affecting treatment outcome and subsequently human health. The Human Microbiome Project (HMP) revived interest in the role of human microbiota in health and disease. Yet, no repository of reported drug-microbe interactions is publicly available, and no attempts have been made to link those interactions to the human microbiome in a structured way. To begin addressing the need for such a crucial and timely resource, we analyzed published experimental data to extract drug-microbe interactions so as to enable the application of emerging HMP knowledge in postgenomics personalized medicine. We hereby report the creation of the PharmacoMicrobiomics Database, which aims to collect, classify, and cross-reference known drug-microbiome interactions and categorize them according to body site and microbial taxonomy. The database is integrated into a web portal that includes a search engine, through which students and scholars can locate drug-microbiome interaction of interest, compiled from and connected to public databases, such as PubMed, PubChem, and Comparative Toxicogenomics. Making these data available is a significant first step towards the prediction of interactions between drugs with similar chemical properties and microbes with similar metabolic abilities. Currently, the PharmacoMicrobiomics Database contains drug-microbiome interactions for more than 60 drugs curated from over 100 research and review articles. Further developments will include the automation of data updating, classification based on drug classes and biochemical pathways, and the participation of the community into data curation and analysis. This work provides a timely and much needed pioneering resource to the global open science community and usefully builds bridges between the rapidly growing fields of pharmacogenomics and human microbiome research. Database URL: http://www.pharmacomicrobiomics.org; Source Code: http://sourceforge.net/projects/ pharmacomicro. Keywords: Biocuration, human microbiome research, personalized medicine, pharmacokinetics, pharmacodynamics, pharmacomicrobiomics, microbiota, relational database.

Application of Novel PCR-Based Methods for Detection, Quantitation, and Phylogenetic Characterization of Sutterella Species in Intestinal Biopsy Samples from Children with Autism and Gastrointestinal Disturbances

ABSTRACTGastrointestinal disturbances are commonly reported in children with autism and may be associated with compositional changes in intestinal bacteria. In a previous report, we surveyed intestinal microbiota in ileal and cecal biopsy samples from children with autism and gastrointestinal dysfunction (AUT-GI) and children with only gastrointestinal dysfunction (Control-GI). Our results demonstrated the presence of members of the family Alcaligenaceae in some AUT-GI children, while no Control-GI children had Alcaligenaceae sequences. Here we demonstrate that increased levels of Alcaligenaceae in intestinal biopsy samples from AUT-GI children result from the presence of high levels of members of the genus Sutterella. We also report the first Sutterella-specific PCR assays for detecting, quantitating, and genotyping Sutterella species in biological and environmental samples. Sutterella 16S rRNA gene sequences were found in 12 of 23 AUT-GI children but in none of 9 Control-GI children. Phylogenetic analysis revealed a predominance of either Sutterella wadsworthensis or Sutterella stercoricanis in 11 of the individual Sutterella-positive AUT-GI patients; in one AUT-GI patient, Sutterella sequences were obtained that could not be given a species-level classification based on the 16S rRNA gene sequences of known Sutterella isolates. Western immunoblots revealed plasma IgG or IgM antibody reactivity to Sutterella wadsworthensis antigens in 11 AUT-GI patients, 8 of whom were also PCR positive, indicating the presence of an immune response to Sutterella in some children.

Probiotics, Prebiotics, and Synbiotics: Gut and Beyond

The human intestinal tract has been colonized by thousands of species of bacteria during the coevolution of man and microbes. Gut-borne microbes outnumber the total number of body tissue cells by a factor of ten. Recent metagenomic analysis of the human gut microbiota has revealed the presence of some 3.3 million genes, as compared to the mere 23 thousand genes present in the cells of the tissues in the entire human body. Evidence for various beneficial roles of the intestinal microbiota in human health and disease is expanding rapidly. Perturbation of the intestinal microbiota may lead to chronic diseases such as autoimmune diseases, colon cancers, gastric ulcers, cardiovascular disease, functional bowel diseases, and obesity. Restoration of the gut microbiota may be difficult to accomplish, but the use of probiotics has led to promising results in a large number of well-designed (clinical) studies. Microbiomics has spurred a dramatic increase in scientific, industrial, and public interest in probiotics and prebiotics as possible agents for gut microbiota management and control. Genomics and bioinformatics tools may allow us to establish mechanistic relationships among gut microbiota, health status, and the effects of drugs in the individual. This will hopefully provide perspectives for personalized gut microbiota management.

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.

The Impact of Gut Microbiota in Human Health and Diseases: Implication for Therapeutic Potential

Humans have and hold 100 trillion intestinal bacteria that are essential for health. For millions of years human-microorganisms interaction has co-evolved, and maintained close symbiotic relationship. Gut bacteria contributes to human health and metabolism, and humans provides the optimum nutrition-rich environment for bacteria. What is the mechanism of the host distinguishing the intestinal bacteria as its cohabiting partner and what kind of benefits does the gut microbiota provide the human are the fundamental questions to be asked and solved in order to make human life a higher quality. This review explains the physiological relationship and mutualism between the host and gut microorganism, and highlights the potential therapeutic approach for treating diseases, maintaining and improving health based on these correlations.

Gut Microbiota-targeted, Whole-Body Systems Biology for Understanding Traditional Chinese Medicine

Abstract Traditional Chinese medicine (TCM) is a medical system with its own theoretical framework focusing on functions at the whole-body level, and it has accumulated abundant clinical experience. However, TCM approaches are empirical, and the manifestations that it reads in human bodies can hardly be communicated in molecular language with modern medicine. Whole-body systems biology considers the human body as a “superorganism,” which consists of cells of both human and symbiotic microorganisms. Taking advantage of “-omic” technologies, biological information in urine, fecal, and blood samples can be profiled as emergent functions of the complex human system for understanding its dynamics in disease and health. This top-down systems biology approach emphasizes the functions of gut microbiota in human health. It is a holistic approach similar to TCM, but it assesses human health with molecular-marker-based methods; therefore, it can serve as a bridge between TCM and western medical science. This article summarizes the concepts, methodologies, clinical applications, and advantages of “functional metagenomics,” a whole-body systems-biology platform, as a new research strategy for modernization of TCM.

The Human Gutome: Nutrigenomics of the Host–Microbiome Interactions

Demonstrating the importance of the gut microbiota in human health and well-being represents a major transformational task in both medical and nutritional research. Owing to the high-throughput -omics methodologies, the complexity, evolution with age, and individual nature of the gut microflora have been more thoroughly investigated. The balance between this complex community of gut bacteria, food nutrients, and intestinal genomic and physiological milieu is increasingly recognized as a major contributor to human health and disease. This article discusses the "gutome," that is, nutritional systems biology of gut microbiome and host-microbiome interactions. We examine the novel ways in which the study of the human gutome, and nutrigenomics more generally, can have translational and transformational impacts in 21st century practice of biomedicine. We describe the clinical context in which experimental methodologies, as well as data-driven and process-driven approaches are being utilized in nutrigenomics and microbiome research. We underscore the pivotal importance of the gutome as a common platform for sharing data in the emerging field of the integrated metagenomics of gut pathophysiology. This vision needs to be articulated in a manner that recognizes both the omics biotechnology nuances and the ways in which nutrigenomics science can effectively inform population health and public policy, and vice versa.

Metagenomic study of the human skin microbiome associated with acne

The human microbiota contributes to our normal postnatal development and plays a significant role in defining our physiology. To understand the role of microbiota in human health and disease, we study the skin microbiome in pilosebaceous units (hair follicles) and its association with acne.Acne is one of the most common skin diseases. Although its etiology still needs to be defined, a bacterial factor has been suggested in the development of the disease. In fact, antibiotic therapy targeting Propionibacterium acnes has been a mainstay treatment for more than 30 years.Our preliminary study shows that the microcomedone, a specialized skin compartment where acne arises, has a tractable microbiome, with a single dominant species, P. acnes. This system offers a unique advantage allowing in-depth analysis of a human microbiome at the subspecies level by sequencing. Our preliminary study suggests that the microbiome associated with acne offers promise for understanding the correlation between the composition of the microbiome and human health and disease.The goal of the project is to determine whether the microbiota in the pilosebaceous units contributes to acne. We plan to investigate the microbiome associated with acne in three directions. First, we plan to investigate the strain diversity of P. acnes in a disease cohort and a normal cohort and examine whether certain strains of P. acnes are correlated with the disease. Second, we plan to investigate the non- P. acnes microbes in microcomedones and disease lesions and examine whether they correlate with acne pathogenesis. Third, we will examine the interactions between the microbes and the host by transcriptional profiling of both the microbiota and the host.During the first year of this project, two main questions were asked. 1. Are certain strains of P. acnes associated with acne, but rarely found in normal individuals? 2. If specific strains are associated with acne, what are the differences in their genetic composition compared to other P. acnes strains that are not associated with acne? We collected microcomedone samples from more than 100 subjects, including acne patients and normal individuals. Genomic DNA was extracted from each sample, and 16S rDNA was amplified using universal primers (8F and 1510R), cloned and sequenced using Sanger method. Approximately 384 near full length 16S rDNA sequences were obtained for each sample. Some of the microcomedone samples were also cultured under anaerobic condition to isolate different P. acnes strains. Sixty-eight isolates were selected for whole genome shotgun sequencing using Solexa/Illumina platform. By the end of the first year of the project, we completed the sequencing of more than 40,000 16S rDNA clones and 68 genomes of P. acnes isolates.

Metagenomic study of the human skin microbiome associated with acne

AbstractThe human microbiota contributes to our normal postnatal development and plays a significant role in defining our physiology. To understand the role of microbiota in human health and disease, we study the skin microbiome in pilosebaceous units (hair follicles) and its association with acne.Acne is one of the most common skin diseases. Although its etiology still needs to be defined, a bacterial factor has been suggested in the development of the disease. In fact, antibiotic therapy targeting Propionibacterium acnes has been a mainstay treatment for more than 30 years.Our preliminary study shows that the microcomedone, a specialized skin compartment where acne arises, has a tractable microbiome, with a single dominant species, P. acnes. This system offers a unique advantage allowing in-depth analysis of a human microbiome at the subspecies level by sequencing. Our preliminary study suggests that the microbiome associated with acne offers promise for understanding the correlation between the composition of the microbiome and human health and disease.The goal of the project is to determine whether the microbiota in the pilosebaceous units contributes to acne. We plan to investigate the microbiome associated with acne in three directions. First, we plan to investigate the strain diversity of P. acnes in a disease cohort and a normal cohort and examine whether certain strains of P. acnes are correlated with the disease. Second, we plan to investigate the non- P. acnes microbes in microcomedones and disease lesions and examine whether they correlate with acne pathogenesis. Third, we will examine the interactions between the microbes and the host by transcriptional profiling of both the microbiota and the host.During the first year of this project, two main questions were asked. 1. Are certain strains of P. acnes associated with acne, but rarely found in normal individuals? 2. If specific strains are associated with acne, what are the differences in their genetic composition compared to other P. acnes strains that are not associated with acne? We collected microcomedone samples from more than 100 subjects, including acne patients and normal individuals. Genomic DNA was extracted from each sample, and 16S rDNA was amplified using universal primers (8F and 1510R), cloned and sequenced using Sanger method. Approximately 384 near full length 16S rDNA sequences were obtained for each sample. Some of the microcomedone samples were also cultured under anaerobic condition to isolate different P. acnes strains. Sixty-eight isolates were selected for whole genome shotgun sequencing using Solexa/Illumina platform. By the end of the first year of the project, we completed the sequencing of more than 40,000 16S rDNA clones and 68 genomes of P. acnes isolates.

Gut microbiota: a potential new territory for drug targeting

The significant involvement of the gut microbiota in human health and disease suggests that manipulation of commensal microbial composition through combinations of antibiotics, probiotics and prebiotics could be a novel therapeutic approach. A systems perspective is needed to help understand the complex host-bacteria interactions and their association with pathophysiological phenotypes so that alterations in the composition of the gut microbiota in disease states can be reversed. In this article, we describe the therapeutic rationale and potential for targeting the gut microbiota, and discuss strategies and systems-oriented technologies for achieving this goal.

The Food, GI-tract Functionality and Human Health Cluster: PROEUHEALTH and Beyond

Probiotics have become an important and rapidly expanding segment of the food market as processed food manufacturers seek to improve market share by promoting the health benefits provided by functional ingredients in their products. Scientific progress has been expanding the knowledge on how foods influence consumers in relation to specific health parameters. Probiotic foods targeted towards improving the balance and activity of the intestinal microbiota currently provide the largest segment of the functional food market in Europe, Japan and Australia. The human gastrointestinal (GI)-tract is the metabolically most active body organ and is the prime target of present and future functional foods. It is the primary site of food conversion and uptake but also the location where the mucosal immune system is primed and various local and systemic disorders become manifest. While sterile at birth, the GI-tract is colonized by a myriad of microbes / collectively called microbiota / that contribute towards food conversion, digestion, communication with the host and induction of specific biological responses contributing to many critical physiological functions. Hence, the GI-tract represents the site where the host’s well-being is mostly affected by food intake in both a direct way but also through modulating the interplay between gut microbes and the host. Various sequential steps are essential in the development of efficacious functional foods. A prerequisite for mechanistic studies of action is an understanding of the composition and activity of the intestinal microbiota as well as interactions with the host in both healthy and diseased individuals. High-throughput molecular methods are required to examine the intestinal microbiota and to track the location and activity of probiotic strains in the intestinal tract. An understanding of the mechanisms by which probiotics exert beneficial effects allows the selection of strains of lactic acid bacteria (LAB) that can be tested in human clinical studies following demonstration of their safety. An important area of research includes the technologies to maximize the stability of functional traits of probiotics during manufacture, formulation, storage and in the intestinal tract. Finally, an understanding of the most appropriate approaches to communicate the benefits of the probiotic foods to consumers and the influence of health messages on consumer choice is essential to ensure that products are appropriately applied and targeted to benefit specific populations. The Food, GI-tract Functionality and Human Health Cluster has brought together 64 research partners from 16 European countries in the quest to obtain greater knowledge of the role of the intestinal microbiota in human health and disease and to develop new functional foods and therapies. The reseach started in February 2001, it will run over 5 years ending in 2005 and is subsidized by the European Commission’s 5th Framework, Quality of Life and Management of Living Resources Programme. Eight complementary multicentre European projects are included in the cluster. They cover all aspects of the development of new probiotic foods, from designing molecular tools to study the ecology of the intestinal microbiota, to understanding mechanisms of bacterium / host interactions, providing solutions to food technology issues, and finally to conducting human clinical trials to assess efficacy in preventing or treating disease. The following research areas demonstrate the impact of the ongoing cluster: