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.
"Both protective immune responses and dysregulation during autoimmunity are activated by signals initiated by innate immunity and driven by microbial stimuli . Many studies have thus investigated microbial function in the gut microbiome in these diverse autoimmune diseases, with several recent examples including inflammatory bowel disease [31,32,86,87], rheumatoid arthritis , and allergy and atopy [18,42,88] (as described earlier), as well as metabolic syndrome [89,90] and neurological disorders [15,47-49]. As a T-cell-mediated metabolic disease, type 1 diabetes is another prime candidate for involvement of the gut microbiota [5,10,91]. "
[Show abstract][Hide abstract] 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. DOI:10.1186/gm469 · 5.34 Impact Factor
"Specific bacteria also induce the formation of regulatory T-lymphocytes that suppress potentially dangerous immune responses that can cause inflammatory bowel disease (Mazmanian et al. 2008; Chow et al. 2010). The role of symbiotic microbes in mammalian disease prevention is well recognized today (Mazmanian et al. 2008; Lee and Mazmanian 2010; Ballal et al. 2011), and new metagenomic sequencing continues to provide new insights into the relationships between human physiological states and the microbial populations found in humans (Turnbaugh and Gordon 2009; Greenblum et al. 2012). And there is reciprocity. "
[Show abstract][Hide abstract] ABSTRACT: The notion of the "biological individual" is crucial to studies of genetics, immunology, evolution, development, anatomy, and physiology. Each of these biological subdisciplines has a specific conception of individuality, which has historically provided conceptual contexts for integrating newly acquired data. During the past decade, nucleic acid analysis, especially genomic sequencing and high-throughput RNA techniques, has challenged each of these disciplinary definitions by finding significant interactions of animals and plants with symbiotic microorganisms that disrupt the boundaries that heretofore had characterized the biological individual. Animals cannot be considered individuals by anatomical or physiological criteria because a diversity of symbionts are both present and functional in completing metabolic pathways and serving other physiological functions. Similarly, these new studies have shown that animal development is incomplete without symbionts. Symbionts also constitute a second mode of genetic inheritance, providing selectable genetic variation for natural selection. The immune system also develops, in part, in dialogue with symbionts and thereby functions as a mechanism for integrating microbes into the animal-cell community. Recognizing the "holobiont"--the multicellular eukaryote plus its colonies of persistent symbionts--as a critically important unit of anatomy, development, physiology, immunology, and evolution opens up new investigative avenues and conceptually challenges the ways in which the biological subdisciplines have heretofore characterized living entities.
The Quarterly Review of Biology 12/2012; 87(4):325-41. DOI:10.1086/668166 · 4.89 Impact Factor
"Of particular interest are investigations of microflora community structure among hosts. One of the underlying reasons for this interest is the hypothesis that observed relationships between hosts and their microbial communities are the result of factors that promote symbiotic relationships via natural selection acting on both hosts and microbial communities (Ballal et al. 2011). The factors (explanatory variables) that are thought to shape observed structure can be considered as temporally stratified, with the evolutionary time represented in the host sample being the broadest measurable variable, whereas lifespan processes of an individual host (physiological changes associated with growth and development, health status, etc.) represent the most recent perceivable temporal aspect of the data. "
[Show abstract][Hide abstract] ABSTRACT: Metagenomic methods provide an experimental approach to inform the relationships between hosts and their microbial inhabitants. Previous studies have provided the conceptual realization that microbiomes are dynamic among hosts and the intimacy of relation between micro- and macroorganisms. Here, we present an intestinal microflora community analysis for members of the order Chiroptera and investigate the relative influence of variables in shaping observed microbiome relationships. The variables ranged from those considered to have ancient and long-term influences (host phylogeny and life history) to the relatively transient variable of host reproductive condition. In addition, collection locality data, representing the geographic variable, were included in analyses. Results indicate a complex influence of variables in shaping sample relationships in which signal for host phylogeny is recovered at broad taxonomic levels (family), whereas intrafamilial analyses disclosed various degrees of resolution for the remaining variables. Although cumulative probabilities of assignment indicated both reproductive condition and geography influenced relationships, comparison of ecological measures among groups revealed statistical differences between most variable classifications. For example, ranked ecological diversity was associated with host phylogeny (deeper coalescences among families were associated with more microfloral diversity), dietary strategy (herbivory generally retained higher diversity than carnivory) and reproductive condition (reproductively active females displayed more diverse microflora than nonreproductive conditions). Overall, the results of this study describe a complex process shaping microflora communities of wildlife species as well as provide avenues for future research that will further inform the nature of symbiosis between microflora communities and hosts.
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