Host and gut microbiota symbiotic factors: lessons from inflammatory bowel disease and successful symbionts.
ABSTRACT Humans are colonized by a diverse collection of microbes, the largest numbers of which reside in the distal gut. The vast majority of humans coexist in a beneficial equilibrium with these microbes. However, disruption of this mutualistic relationship can manifest itself in human diseases such as inflammatory bowel disease. Thus the study of inflammatory bowel disease and its genetics can provide insight into host pathways that mediate host-microbiota symbiosis. Bacteria of the human intestinal ecosystem face numerous challenges imposed by human dietary intake, the mucosal immune system, competition from fellow members of the gut microbiota, transient ingested microbes and invading pathogens. Considering features of human resident gut bacteria provides the opportunity to understand how microbes have achieved their symbiont status. While model symbionts have provided perspective into host-microbial homeostasis, high-throughput approaches are becoming increasingly practical for functionally characterizing the gut microbiota as a community.
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ABSTRACT: The microbial residents of the human gut are a major factor in the development and lifelong maintenance of health. The gut microbiota differs to a large degree from person to person and has an important influence on health and disease due to its interaction with the human immune system. Its overall composition and microbial ecology have been implicated in many autoimmune diseases, and it represents a particularly important area for translational research as a new target for diagnostics and therapeutics in complex inflammatory conditions. Determining the biomolecular mechanisms by which altered microbial communities contribute to human disease will be an important outcome of current functional studies of the human microbiome. In this review, we discuss functional profiling of the human microbiome using metagenomic and metatranscriptomic approaches, focusing on the implications for inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis. Common themes in gut microbial ecology have emerged among these diverse diseases, but they have not yet been linked to targetable mechanisms such as microbial gene and genome composition, pathway and transcript activity, and metabolism. Combining these microbial activities with host gene, transcript and metabolic information will be necessary to understand how and why these complex interacting systems are altered in disease-associated inflammation.Genome Medicine 07/2013; 5(7):65. · 4.94 Impact Factor
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ABSTRACT: A central challenge in microbial community ecology is the delineation of appropriate units of biodiversity, which can be taxonomic, phylogenetic or functional in nature. The term "community" is applied ambiguously; in some cases the term refers simply to a set of observed entities, while in other cases it requires that these entities interact with one another. Microbes can rapidly gain and lose genes, potentially decoupling community roles from taxonomic and phylogenetic groupings. Trait-based approaches offer a useful alternative, but many traits can be defined based on gene functions, metabolic modules, and genomic properties, and the optimal set of traits to choose is often not obvious. An analysis that considers taxon assignment and traits in concert may be ideal, with the strengths of each approach offsetting the weaknesses of the other. Individual genes also merit consideration as entities in an ecological analysis, with characteristics such as diversity, turnover, and interactions modeled using genes rather than organisms as entities. We identify some promising avenues of research that are likely to yield a deeper understanding of microbial communities that shift from observation-based questions of "Who is There?" and "What Are They Doing?" to the mechanistically driven "How Will They Respond?" This article is protected by copyright. All rights reserved.FEMS microbiology reviews 08/2013; · 10.96 Impact Factor
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ABSTRACT: Molecular analyses of symbiotic relationships are challenging our biological definitions of individuality and supplanting them with a new notion of normal part-whole relationships. This new notion is that of a 'holobiont', a consortium of organisms that becomes a functionally integrated 'whole'. This holobiont includes the zoological organism (the 'animal') as well as its persistent microbial symbionts. This new individuality is seen on anatomical and physiological levels, where a diversity of symbionts form a new 'organ system' within the zoological organism and become integrated into its metabolism and development. Moreover, as in normal development, there are reciprocal interactions between the 'host' organism and its symbionts that alter gene expression in both sets of cells. The immune system, instead of being seen as functioning solely to keep microbes out of the body, is also found to develop, in part, in dialogue with symbionts. Moreover, the immune system is actively involved in the colonization of the zoological organism, functioning as a mechanism for integrating microbes into the animal-cell community. Symbionts have also been found to constitute a second mode of genetic inheritance, providing selectable genetic variation for natural selection. We develop, grow and evolve as multi-genomic consortia/teams/ecosystems.Journal of Biosciences 04/2014; 39(2):201-9. · 1.76 Impact Factor