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Together, they form a suite of complementary approaches to genetically engineer undomesticated gut commensal bacteria and probe the functional genetic networks in the gut microbiome, which will enhance our understanding of microbiome ecology and host-microbiome interactions. In addition, the expanded range of genetic manipulations made possible by these tools may enable production of more diverse, perhaps personalized, probiotics containing engineered functions, such as sensing disease markers or drug delivery.
The 21st century has witnessed a complete revolution in the understanding and description of bacteria in eco- systems and microbial assemblages, and how they are regulated by complex interactions among microbes, hosts, and environments. The human organism is no longer considered a monolithic assembly of tissues, but is instead a true ecosystem composed of human cells, bacteria, fungi, algae, and viruses. As such, humans are not unlike other complex ecosystems containing microbial assemblages observed in the marine and earth environments. They all share a basic functional principle: Chemical communication is the universal language that allows such groups to properly function together. These chemical networks regulate interactions like metabolic exchange, antibiosis and symbiosis, and communication. The National Academies of Sciences, Engineering, and Medicine's Chemical Sciences Roundtable organized a series of four seminars in the autumn of 2016 to explore the current advances, opportunities, and challenges toward unveiling this "chemical dark matter" and its role in the regulation and function of different ecosystems. The first three focused on specific ecosystemsâ€"earth, marine, and humanâ€"and the last on all microbiome systems. This publication summarizes the presentations and discussions from the seminars.
The mammalian gut is residence to a large microbial community whose collective set of millions of genes (microbiome) encodes a vast array of functions, including many that process dietary components. Few tools are available to change the microbiome's properties to promote host health because the factors governing community assembly and operation are poorly understood. My thesis focused on the impact of one factor, host diet. I used a variety of experimental and computational methods to perform a comparative metagenomic study of the fecal communities of 39 diverse mammals to assess microbiome variation. These animals included herbivores, omnivores and carnivores representing different portions of the mammalian tree, Targeted sequencing of the bacterial 16S rRNA gene and shotgun gene sequencing of total fecal DNA revealed that animals with similar diets possessed similar microbiomes, both in terms of bacterial species detected and the functions that their genomes encoded. A large number of genes were found in all gut microbiomes, but the relative abundance of many traits was differentially represented in carnivorous compared to herbivorous hosts, demonstrating that diet can shape a microbiome. We next studied microbiome variation within a single host species consuming a range of diets, using a population of 18 calorie-restricted adult humans with carefully recorded dietary intake. Even in these free-living, unrelated individuals, the amount of protein and dietary fiber consumed was significantly correlated with the variation in the gut metagenomes. My second study addressed the period of dramatic dietary variation in human life when breast fed infants are weaned. The study population was a birth cohort of 103 children born in Bangladesh, some of who developed malnutrition during the first two years of life. My results demonstrate that despite large inter-personal variation, common patterns are found in the establishment of bacterial species and functions as the children age. The data revealed a developmental pattern of human gut microbiome functional assembly. This was exemplified by the emergence of glycan degradation capacity in all children studied. Some of the taxonomic and functional changes can be correlated with the host's diet, but many properties of the developing infant microbiome cannot be explained by diet alone.
Examining the enormous potential of microbiome manipulation to improve health Associations between the composition of the intestinal microbiome and many human diseases, including inflammatory bowel disease, cardiovascular disease, metabolic disorders, and cancer, have been elegantly described in the past decade. Now, whole-genome sequencing, bioinformatics, and precision gene-editing techniques are being combined with centuries-old therapies, such as fecal microbiota transplantation, to translate current research into new diagnostics and therapeutics to treat complex diseases. Bugs as Drugs provides a much-needed overview of microbes in therapies and will serve as an excellent resource for scientists and clinicians as they carry out research and clinical studies on investigating the roles the microbiota plays in health and disease. In Bugs as Drugs, editors Robert A. Britton and Patrice D. Cani have assembled a fascinating collection of reviews that chart the history, current efforts, and future prospects of using microorganisms to fight disease and improve health. Sections cover traditional uses of probiotics, next-generation microbial therapeutics, controlling infectious diseases, and indirect strategies for manipulating the host microbiome. Topics presented include: How well-established probiotics support and improve host health by improving the composition of the intestinal microbiota of the host and by modulating the host immune response. The use of gene editing and recombinant DNA techniques to create tailored probiotics and to characterize next-generation beneficial microbes. For example, engineering that improves the anti-inflammatory profile of probiotics can reduce the number of colonic polyps formed, and lactobacilli can be transformed into targeted delivery systems carrying therapeutic proteins or bioengineered bacteriophage. The association of specific microbiota composition with colorectal cancer, liver diseases, osteoporosis, and inflammatory bowel disease. The gut microbiota has been proposed to serve as an organ involved in regulation of inflammation, immune function, and energy homeostasis. Fecal microbiota transplantation as a promising treatment for numerous diseases beyond C. difficile infection. Practical considerations for using fecal microbiota transplantation are provided, while it is acknowledged that more high-quality evidence is needed to ascertain the importance of strain specificity in positive treatment outcomes. Because systems biology approaches and synthetic engineering of microbes are now high-throughput and cost-effective, a much wider range of therapeutic possibilities can be explored and vetted.
The book provides an overview on how the microbiome contributes to human health and disease. The microbiome has also become a burgeoning field of research in medicine, agriculture & environment. The readers will obtain profound knowledge on the connection between intestinal microbiota and immune defense systems, medicine, agriculture & environment. The book may address several researchers, clinicians and scholars working in biomedicine, microbiology and immunology. The application of new technologies has no doubt revolutionized the research initiatives providing new insights into the dynamics of these complex microbial communities and their role in medicine, agriculture & environment shall be more emphasized. Drawing on broad range concepts of disciplines and model systems, this book primarily provides a conceptual framework for understanding these human-microbe, animal-microbe & plant-microbe, interactions while shedding critical light on the scientific challenges that lie ahead. Furthermore this book explains why microbiome research demands a creative and interdisciplinary thinking—the capacity to combine microbiology with human, animal and plant physiology, ecological theory with immunology, and evolutionary perspectives with metabolic science.This book provides an accessible and authoritative guide to the fundamental principles of microbiome science, an exciting and fast-emerging new discipline that is reshaping many aspects of the life sciences. These microbial partners can also drive ecologically important traits, from thermal tolerance to diet in a typical immune system, and have contributed to animal and plant diversification over long evolutionary timescales. Also this book explains why microbiome research presents a more complete picture of the biology of humans and other animals, and how it can deliver novel therapies for human health and new strategies.
Scientific advances over the past several decades have accelerated the ability to engineer existing organisms and to potentially create novel ones not found in nature. Synthetic biology, which collectively refers to concepts, approaches, and tools that enable the modification or creation of biological organisms, is being pursued overwhelmingly for beneficial purposes ranging from reducing the burden of disease to improving agricultural yields to remediating pollution. Although the contributions synthetic biology can make in these and other areas hold great promise, it is also possible to imagine malicious uses that could threaten U.S. citizens and military personnel. Making informed decisions about how to address such concerns requires a realistic assessment of the capabilities that could be misused. Biodefense in the Age of Synthetic Biology explores and envisions potential misuses of synthetic biology. This report develops a framework to guide an assessment of the security concerns related to advances in synthetic biology, assesses the levels of concern warranted for such advances, and identifies options that could help mitigate those concerns.
The Food Forum convened a public workshop on February 22-23, 2012, to explore current and emerging knowledge of the human microbiome, its role in human health, its interaction with the diet, and the translation of new research findings into tools and products that improve the nutritional quality of the food supply. The Human Microbiome, Diet, and Health: Workshop Summary summarizes the presentations and discussions that took place during the workshop. Over the two day workshop, several themes covered included: The microbiome is integral to human physiology, health, and disease. The microbiome is arguably the most intimate connection that humans have with their external environment, mostly through diet. Given the emerging nature of research on the microbiome, some important methodology issues might still have to be resolved with respect to undersampling and a lack of causal and mechanistic studies. Dietary interventions intended to have an impact on host biology via their impact on the microbiome are being developed, and the market for these products is seeing tremendous success. However, the current regulatory framework poses challenges to industry interest and investment.
A great number of diverse microorganisms inhabit the human body and are collectively referred to as the human microbiome. Until recently, the role of the human microbiome in maintaining human health was not fully appreciated. Today, however, research is beginning to elucidate associations between perturbations in the human microbiome and human disease and the factors that might be responsible for the perturbations. Studies have indicated that the human microbiome could be affected by environmental chemicals or could modulate exposure to environmental chemicals. Environmental Chemicals, the Human Microbiome, and Health Risk presents a research strategy to improve our understanding of the interactions between environmental chemicals and the human microbiome and the implications of those interactions for human health risk. This report identifies barriers to such research and opportunities for collaboration, highlights key aspects of the human microbiome and its relation to health, describes potential interactions between environmental chemicals and the human microbiome, reviews the risk-assessment framework and reasons for incorporating chemicalâ€"microbiome interactions.
Beginning with the germ theory of disease in the 19th century and extending through most of the 20th century, microbes were believed to live their lives as solitary, unicellular, disease-causing organisms . This perception stemmed from the focus of most investigators on organisms that could be grown in the laboratory as cellular monocultures, often dispersed in liquid, and under ambient conditions of temperature, lighting, and humidity. Most such inquiries were designed to identify microbial pathogens by satisfying Koch's postulates.3 This pathogen-centric approach to the study of microorganisms produced a metaphorical "war" against these microbial invaders waged with antibiotic therapies, while simultaneously obscuring the dynamic relationships that exist among and between host organisms and their associated microorganisms-only a tiny fraction of which act as pathogens. Despite their obvious importance, very little is actually known about the processes and factors that influence the assembly, function, and stability of microbial communities. Gaining this knowledge will require a seismic shift away from the study of individual microbes in isolation to inquiries into the nature of diverse and often complex microbial communities, the forces that shape them, and their relationships with other communities and organisms, including their multicellular hosts. On March 6 and 7, 2012, the Institute of Medicine's (IOM's) Forum on Microbial Threats hosted a public workshop to explore the emerging science of the "social biology" of microbial communities. Workshop presentations and discussions embraced a wide spectrum of topics, experimental systems, and theoretical perspectives representative of the current, multifaceted exploration of the microbial frontier. Participants discussed ecological, evolutionary, and genetic factors contributing to the assembly, function, and stability of microbial communities; how microbial communities adapt and respond to environmental stimuli; theoretical and experimental approaches to advance this nascent field; and potential applications of knowledge gained from the study of microbial communities for the improvement of human, animal, plant, and ecosystem health and toward a deeper understanding of microbial diversity and evolution. The Social Biology of Microbial Communities: Workshop Summary further explains the happenings of the workshop.