The large majority of studies on the role of the microbiome in the pathogenesis of disease are correlative and preclinical; several have influenced clinical practice.
Human-associated microbes have ...primarily been viewed through the lens of a single species and its environment. Advances in culture-independent technologies have shown the enormous diversity, functional capacity, and age-associated dynamics of the human microbiome (see the Glossary). A large number of diverse microbial species reside in the distal gastrointestinal tract, and gut microbiota dysbiosis — imbalances in the composition and function of these intestinal microbes — is associated with diseases ranging from localized gastroenterologic disorders to neurologic, respiratory, metabolic, hepatic, and cardiovascular illnesses. Much effort is currently concentrated on exploring potential causality and related microbiota-mediated disease mechanisms, with the hope that an . . .
Over the past decade, our view of human-associated microbes has expanded beyond that of a few species toward an appreciation of the diverse and niche-specialized microbial communities that develop in ...the human host with chronological age. The largest reservoir of microbes exists in the distal gastrointestinal tract, both in the lumen, where microbes facilitate primary and secondary metabolism, and on mucosal surfaces, where they interact with host immune cell populations. While local microbial-driven immunomodulation in the gut is well described, more recent studies have demonstrated a role for the gut microbiome in influencing remote organs and mucosal and hematopoietic immune function. Unsurprisingly, therefore, perturbation to the composition and function of the gut microbiota has been associated with chronic diseases ranging from gastrointestinal inflammatory and metabolic conditions to neurological, cardiovascular, and respiratory illnesses. Considerable effort is currently focused on understanding the natural history of microbiome development in humans in the context of health outcomes, in parallel with improving our knowledge of microbiome-host molecular interactions. These efforts ultimately aim to develop effective approaches to rehabilitate perturbed human microbial ecosystems as a means to restore health or prevent disease. This review details the role of the gut microbiome in modulating host health with a focus on immunomodulation and discusses strategies for manipulating the gut microbiome for the management or prevention of chronic inflammatory conditions.
According to World Health Organization statistics of 2011, infectious diseases remain in the top five causes of mortality worldwide. However, despite sophisticated research tools for microbial ...detection, rapid and accurate molecular diagnostics for identification of infection in humans have not been extensively adopted. Time-consuming culture-based methods remain to the forefront of clinical microbial detection. The 16S rRNA gene, a molecular marker for identification of bacterial species, is ubiquitous to members of this domain and, thanks to ever-expanding databases of sequence information, a useful tool for bacterial identification. In this study, we assembled an extensive repository of clinical isolates (n = 617), representing 30 medically important pathogenic species and originally identified using traditional culture-based or non-16S molecular methods. This strain repository was used to systematically evaluate the ability of 16S rRNA for species level identification. To enable the most accurate species level classification based on the paucity of sequence data accumulated in public databases, we built a Naïve Bayes classifier representing a diverse set of high-quality sequences from medically important bacterial organisms. We show that for species identification, a model-based approach is superior to an alignment based method. Overall, between 16S gene based and clinical identities, our study shows a genus-level concordance rate of 96% and a species-level concordance rate of 87.5%. We point to multiple cases of probable clinical misidentification with traditional culture based identification across a wide range of gram-negative rods and gram-positive cocci as well as common gram-negative cocci.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Asthma and atopy, classically associated with hyper-activation of the T helper 2 (Th2) arm of adaptive immunity, are among the most common chronic illnesses worldwide. Emerging evidence relates atopy ...and asthma to the composition and function of the human microbiome, the collection of microbes that reside in and on and interact with the human body. The ability to interrogate microbial ecology of the human host is due in large part to recent technological developments that permit identification of microbes and their products using culture-independent molecular detection techniques. In this review we explore the roles of respiratory, gut, and environmental microbiomes in asthma and allergic disease development, manifestation, and attenuation. Though still a relatively nascent field of research, evidence to date suggests that the airway and/or gut microbiome may represent fertile targets for prevention or management of allergic asthma and other diseases in which adaptive immune dysfunction is a prominent feature.
Asthma and atopy are common chronic illnesses, particularly prevalent in westernized nations. Fujimura and Lynch explore the emerging relationships between respiratory, gastrointestinal, and environmental microbiomes in asthma and atopy development, manifestation, and attenuation.
States of oral health and disease reflect the compositional and functional capacities of, as well as the interspecies interactions within, the oral microbiota. The oral cavity exists as a highly ...dynamic microbial environment that harbors many distinct substrata and microenvironments that house diverse microbial communities. Specific to the oral cavity, the nonshedding dental surfaces facilitate the development of highly complex polymicrobial biofilm communities, characterized not only by the distinct microbes comprising them, but cumulatively by their activities. Adding to this complexity, the oral cavity faces near‐constant environmental challenges, including those from host diet, salivary flow, masticatory forces, and introduction of exogenous microbes. The composition of the oral microbiome is shaped throughout life by factors including host genetics, maternal transmission, as well as environmental factors, such as dietary habits, oral hygiene practice, medications, and systemic factors. This dynamic ecosystem presents opportunities for oral microbial dysbiosis and the development of dental and periodontal diseases. The application of both in vitro and culture‐independent approaches has broadened the mechanistic understandings of complex polymicrobial communities within the oral cavity, as well as the environmental, local, and systemic underpinnings that influence the dynamics of the oral microbiome. Here, we review the present knowledge and current understanding of microbial communities within the oral cavity and the influences and challenges upon this system that encourage homeostasis or provoke microbiome perturbation, and thus contribute to states of oral health or disease.
The prevalence of allergy· and asthma has increased significantly over the post several decades, particularly so in industrialized nations where environmental exposures and lifestyles have rapidly ...diverged from those with which humans evolved. Multifactorial and heterogenous, there is an urgent need to understand the origins of allergy and asthma and develop effective interventions for precision treatment and prevention. Epidemiological studies have identified prenatal and early-life exposures that prevent or promote disease in childhood, a number of which exert strong selective pressures on the types, functions, epigenetic modifications, and development of cellular populations (microbial and immune) critical to immune training, function, and asthma pathogenesis.
Bacterial activation of T helper 17 (Th17) cells exacerbates mouse models of autoimmunity, but how human-associated bacteria impact Th17-driven disease remains elusive. We show that human gut ...Actinobacterium Eggerthella lenta induces intestinal Th17 activation by lifting inhibition of the Th17 transcription factor Rorγt through cell- and antigen-independent mechanisms. E. lenta is enriched in inflammatory bowel disease (IBD) patients and worsens colitis in a Rorc-dependent manner in mice. Th17 activation varies across E. lenta strains, which is attributable to the cardiac glycoside reductase 2 (Cgr2) enzyme. Cgr2 is sufficient to induce interleukin (IL)-17a, a major Th17 cytokine. cgr2+ E. lenta deplete putative steroidal glycosides in pure culture; related compounds are negatively associated with human IBD severity. Finally, leveraging the sensitivity of Cgr2 to dietary arginine, we prevented E. lenta-induced intestinal inflammation in mice. Together, these results support a role for human gut bacterial metabolism in driving Th17-dependent autoimmunity.
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•The prevalent gut Actinobacterium Eggerthella lenta activates Th17 cells•E. lenta is associated with human disease and exacerbates colitis in mice•A strain-specific enzyme Cgr2 induces IL-17a via the metabolism of Rorγt inhibitors•Dietary arginine blocks E. lenta-induced intestinal inflammation
Alexander et al. show an autoimmune-associated microbe, Eggerthella lenta, activates Th17 cells and worsens mouse models of colitis. Using strain-level variation, comparative genomics, and bacterial genetics they demonstrate that the cardiac glycoside reductase 2 (Cgr2) enzyme is sufficient for Th17 activation and that elevated dietary arginine blocks E. lenta-induced colitis.
Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development, and dog ownership is associated with a distinct house dust microbial exposure. Here, we ...demonstrate, using murine models, that exposure of mice to dog-associated house dust protects against ovalbumin or cockroach allergen-mediated airway pathology. Protected animals exhibited significant reduction in the total number of airway T cells, down-regulation of Th2-related airway responses, as well as mucin secretion. Following dog-associated dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii . Supplementation of wild-type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii -mediated protection was associated with significant reductions in the total number and proportion of activated CD11c ⁺/CD11b ⁺ and CD11c ⁺/CD8 ⁺ cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct gastrointestinal microbiome composition. Moreover, the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults.
Studying the role of the human microbiome as it relates to human health status has revolutionized our view of microbial community contributions to a large number of diseases, particularly chronic ...inflammatory disorders. The lower gastrointestinal (GI) tract houses trillions of microbial cells representing a large diversity of species in relatively well‐defined phylogenetic ratios that are associated with maintenance of key aspects of host physiology and immune homeostasis. It is not surprising, therefore, that many GI inflammatory diseases, including inflammatory bowel disease (IBD), are associated with substantial changes in the composition of these microbial assemblages, either as a cause or consequence of host inflammatory response. Here we review current knowledge in the emerging field of human microbiome research as it relates to IBD, specifically focusing on Crohn's disease (CD) and ulcerative colitis (UC). We discuss bacteriotherapeutic efforts to restore GI microbial assemblage integrity via probiotic supplementation of IBD patients, and speculate on future directions for the field. (Inflamm Bowel Dis 2011;)
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