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Missing microbes : how the overuse of antibiotics is fueling our modern plagues
\"A critically important and startling look at the harmful effects of overusing antibiotics, from the field's leading expert Tracing one scientist's journey toward understanding the crucial importance of the microbiome, this revolutionary book will take readers to the forefront of trail-blazing research while revealing the damage that overuse of antibiotics is doing to our health: contributing to the rise of obesity, asthma, diabetes, and certain forms of cancer. In Missing Microbes, Dr. Martin Blaser invites us into the wilds of the human microbiome where for hundreds of thousands of years bacterial and human cells have existed in a peaceful symbiosis that is responsible for the health and equilibrium of our body. Now, this invisible eden is being irrevocably damaged by some of our most revered medical advances--antibiotics--threatening the extinction of our irreplaceable microbes with terrible health consequences. Taking us into both the lab and deep into the fields where these troubling effects can be witnessed firsthand, Blaser not only provides cutting edge evidence for the adverse effects of antibiotics, he tells us what we can do to avoid even more catastrophic health problems in the future. \"-- Provided by publisher.
Book
Antibiotic use and its consequences for the normal microbiome
Anti-infectives, including antibiotics, are essentially different from all other drugs; they not only affect the individual to whom they are given but also the entire community, through selection for resistance to their own action. Thus, their use resides at the intersection of personal and public health. Antibiotics can be likened to a four-edged sword against bacteria. The first two edges of the antibiotic sword were identified immediately after their discovery and deployment in that they not only benefit an individual in treating their infection but also benefit the community in preventing the spread of that infectious agent. The third edge was already recognized by Alexander Fleming in 1945 in his Nobel acceptance speech, which warned about the cost to the community of antibiotic resistance that would inevitably evolve and be selected for during clinical practice. We have seen this cost mount up, as resistance curtails or precludes the activities of some of our most effective drugs for clinically important infections. But the fourth edge of the antibiotic sword remained unappreciated until recently, i.e., the cost that an antibiotic exerts on an individual's own health via the collateral damage of the drug on bacteria that normally live on or in healthy humans: our microbiota. These organisms, their genes, metabolites, and interactions with one another, as well as with their host collectively, represent our microbiome. Our relationship with these symbiotic bacteria is especially important during the early years of life, when the adult microbiome has not yet formed.
Journal Article
The human microbiome: at the interface of health and disease
Key Points
The human microbiome and its relationship to disease is a new and rapidly evolving field of study.
The co-evolution between hosts and their microbiomes has led to cooperative interactions in metabolism and homeostasis.
Concepts from community ecology — such as resilience, community disturbances and extinction — are useful in understanding the microbiome.
New computational and statistical tools are being developed to analyse the large sequence data sets that are generated by the increasingly powerful technologies.
The taxonomic composition and functional characteristics of the microbiome may allow individuals to be categorized into different microbial patterns, called enterotypes, in the gastrointestinal tract. Although low-level taxonomy varies substantially among individuals, higher-level taxonomy and functional characteristics seem to be largely preserved.
Many factors affect the composition of the microbiome over the course of a human lifetime. These include inheritance, the mode of infant delivery, diet and age-related changes in adults.
The relationships between the microbiome and several human diseases are being intensively studied for conditions that include colorectal cancer, inflammatory bowel disease and immunologically mediated skin diseases.
Causal relationships for many of the associations between the microbiome and disease states have yet to be proven.
Understanding the links between the microbiome and human disease may provide prophylactic or therapeutic tools to improve human health.
A growing understanding of the relationship between the microbiome and human health is made possible by advances in sequencing technologies and computational tools. These studies highlight how the composition and function of the microbiome varies across individuals and anatomical sites, over time, and also in disease.
Interest in the role of the microbiome in human health has burgeoned over the past decade with the advent of new technologies for interrogating complex microbial communities. The large-scale dynamics of the microbiome can be described by many of the tools and observations used in the study of population ecology. Deciphering the metagenome and its aggregate genetic information can also be used to understand the functional properties of the microbial community. Both the microbiome and metagenome probably have important functions in health and disease; their exploration is a frontier in human genetics.
Journal Article
Fecal Microbiota Transplantation for Dysbiosis — Predictable Risks
The term “dysbiosis” usually refers to a change in the human microbiome from a healthy pattern toward a pattern associated with disease. Although the term is increasingly being used, the definition, not surprisingly, is vague. Yet dysbiosis has become an area of great interest in medical science.
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Important questions are whether we can recognize dysbiosis in patients with particular medical conditions and whether reversing it, if possible, will lead to improved health. We are at the early stages of understanding these concepts. Dysbiosis occurs most evidently in patients with
Clostridioides difficile
infection. In such patients, it is clear that after . . .
Journal Article
Sparse and Compositionally Robust Inference of Microbial Ecological Networks
16S ribosomal RNA (rRNA) gene and other environmental sequencing techniques provide snapshots of microbial communities, revealing phylogeny and the abundances of microbial populations across diverse ecosystems. While changes in microbial community structure are demonstrably associated with certain environmental conditions (from metabolic and immunological health in mammals to ecological stability in soils and oceans), identification of underlying mechanisms requires new statistical tools, as these datasets present several technical challenges. First, the abundances of microbial operational taxonomic units (OTUs) from amplicon-based datasets are compositional. Counts are normalized to the total number of counts in the sample. Thus, microbial abundances are not independent, and traditional statistical metrics (e.g., correlation) for the detection of OTU-OTU relationships can lead to spurious results. Secondly, microbial sequencing-based studies typically measure hundreds of OTUs on only tens to hundreds of samples; thus, inference of OTU-OTU association networks is severely under-powered, and additional information (or assumptions) are required for accurate inference. Here, we present SPIEC-EASI (SParse InversE Covariance Estimation for Ecological Association Inference), a statistical method for the inference of microbial ecological networks from amplicon sequencing datasets that addresses both of these issues. SPIEC-EASI combines data transformations developed for compositional data analysis with a graphical model inference framework that assumes the underlying ecological association network is sparse. To reconstruct the network, SPIEC-EASI relies on algorithms for sparse neighborhood and inverse covariance selection. To provide a synthetic benchmark in the absence of an experimentally validated gold-standard network, SPIEC-EASI is accompanied by a set of computational tools to generate OTU count data from a set of diverse underlying network topologies. SPIEC-EASI outperforms state-of-the-art methods to recover edges and network properties on synthetic data under a variety of scenarios. SPIEC-EASI also reproducibly predicts previously unknown microbial associations using data from the American Gut project.
Journal Article
The theory of disappearing microbiota and the epidemics of chronic diseases
In recent decades, the incidence of many apparently unrelated chronic diseases has markedly increased. Here, I theorize that losses of particular bacterial species of our ancestral microbiota have altered the context in which immunological, metabolic and cognitive development occur in early life, which results in increased disease. This ominous trend suggests that we must refocus efforts to understand and reverse the underlying circumstances that are responsible for our disappearing microbiota.
Journal Article
Role of the microbiome in human development
The host-microbiome supraorganism appears to have coevolved and the unperturbed microbial component of the dyad renders host health sustainable. This coevolution has likely shaped evolving phenotypes in all life forms on this predominantly microbial planet. The microbiota seems to exert effects on the next generation from gestation, via maternal microbiota and immune responses. The microbiota ecosystems develop, restricted to their epithelial niches by the host immune system, concomitantly with the host chronological development, providing early modulation of physiological host development and functions for nutrition, immunity and resistance to pathogens at all ages. Here, we review the role of the microbiome in human development, including evolutionary considerations, and the maternal/fetal relationships, contributions to nutrition and growth. We also discuss what constitutes a healthy microbiota, how antimicrobial modern practices are impacting the human microbiota, the associations between microbiota perturbations, host responses and diseases rocketing in urban societies and potential for future restoration.
Journal Article
The microbiome revolution
The collection of bacteria, viruses, and fungi that live in and on the human body, collectively known as the microbiome, has recently emerged as an important factor in human physiology and disease. The gut in particular is a biological niche that is home to a diverse array of microbes that influence nearly all aspects of human biology through their interactions with their host; new technologies are beginning to reveal important aspects of host-microbe interactions. Articles in this Review series address how perturbations of the microbiota, such as through antibiotic use, influence its overall structure and function; how our microbiome influences the impact of infectious agents, such as C. difficile; how our microbiome mediates metabolism of xenobiotics; how the microbiota contribute to immunity as well as to metabolic and inflammatory diseases; and the role of commensal microbes in oncogenesis.
Journal Article
What are the consequences of the disappearing human microbiota?
The increase in allergic diseases that has occurred in developing countries in recent years has been attributed to a decrease in exposure to the microorganisms in the environment. Blaser and Falkow reflect that this increase, as well as the ongoing obesity epidemic and increased susceptibility to infectious disease, might instead be the result of changes in the human microbiota.
Humans and our ancestors have evolved since the most ancient times with a commensal microbiota. The conservation of indicator species in a niche-specific manner across all of the studied human population groups suggests that the microbiota confer conserved benefits on humans. Nevertheless, certain of these organisms have pathogenic properties and, through medical practices and lifestyle changes, their prevalence in human populations is changing, often to an extreme degree. In this Essay, we propose that the disappearance of these ancestral indigenous organisms, which are intimately involved in human physiology, is not entirely beneficial and has consequences that might include post-modern conditions such as obesity and asthma.
Journal Article