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Immunostimulation in the era of the metagenome.

ABSTRACT: Microbes are increasingly being implicated in autoimmune disease. This calls for a re-evaluation of how these chronic inflammatory illnesses are routinely treated. The standard of care for autoimmune disease remains the use of medications that slow the immune response, while treatments aimed at eradicating microbes seek the exact opposite-stimulation of the innate immune response. Immunostimulation is complicated by a cascade of sequelae, including exacerbated inflammation, which occurs in response to microbial death. Over the past 8 years, we have collaborated with American and international clinical professionals to research a model-based treatment for inflammatory disease. This intervention, designed to stimulate the innate immune response, has required a reevaluation of disease progression and amelioration. Paramount is the inherent conflict between palliation and microbicidal efficacy. Increased microbicidal activity was experienced as immunopathology-a temporary worsening of symptoms. Further studies are needed, but they will require careful planning to manage this immunopathology.

SUBMITTER: Proal AD

PROVIDER: S-EPMC4076734 | biostudies-other | 2011 May

REPOSITORIES: biostudies-other

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Project description:In the collective genomes (the metagenome) of the microorganisms inhabiting the Earth's diverse environments is written the history of life on this planet. New molecular tools developed and used for the past 15 years by microbial ecologists are facilitating the extraction, cloning, screening, and sequencing of these genomes. This approach allows microbial ecologists to access and study the full range of microbial diversity, regardless of our ability to culture organisms, and provides an unprecedented access to the breadth of natural products that these genomes encode. However, there is no way that the mere collection of sequences, no matter how expansive, can provide full coverage of the complex world of microbial metagenomes within the foreseeable future. Furthermore, although it is possible to fish out highly informative and useful genes from the sea of gene diversity in the environment, this can be a highly tedious and inefficient procedure. Microbial ecologists must be clever in their pursuit of ecologically relevant, valuable, and niche-defining genomic information within the vast haystack of microbial diversity. In this report, we seek to describe advances and prospects that will help microbial ecologists glean more knowledge from investigations into metagenomes. These include technological advances in sequencing and cloning methodologies, as well as improvements in annotation and comparative sequence analysis. More significant, however, will be ways to focus in on various subsets of the metagenome that may be of particular relevance, either by limiting the target community under study or improving the focus or speed of screening procedures. Lastly, given the cost and infrastructure necessary for large metagenome projects, and the almost inexhaustible amount of data they can produce, trends toward broader use of metagenome data across the research community coupled with the needed investment in bioinformatics infrastructure devoted to metagenomics will no doubt further increase the value of metagenomic studies in various environments.

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Immunostimulation in the era of the metagenome.

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