Translational research : the journal of laboratory and clinical medicine
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Among the many areas being revolutionized by the recent introduction of culture-independent microbial identification techniques is investigation of the relationship between close contact with large animals, antibiotics, breast feeding, mode of birth, and other exposures during infancy as related to a reduced risk of asthma and allergic disease. These exposures were originally clustered under the "Hygiene Hypothesis" which has evolved into the "Microbiota Hypothesis". This review begins by summarizing epidemiologic studies suggesting that the common feature of these allergy risk-related exposures is their influence on the founding and early development of a child's gut microbiota. ⋯ Finally, selected mouse and human studies are presented which begin to corroborate the protective exposures identified in epidemiologic studies by elucidating mechanisms through which microbes can alter immune development and function. These microbially driven immune alterations demonstrate that microbial exposures in many cases could alter the risk of subsequent allergic disease and asthma. Hopefully, a better understanding of how microbes influence allergic disease will lead to safe and effective methods for reducing the prevalence of all forms of allergic disease.
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In the past several years, advances in sequencing platforms and bioinformatics have transformed our understanding of the relationship between microbial ecology and human health. Both the normal and diseased lung are host to hundreds of bacterial genera, blurring the lines between "colonization" and "infection". However, whereas in health the respiratory microbiome is determined primarily by the dynamic balance of immigration and elimination, in chronic disease conditions become much more favorable for the reproduction of resident bacteria. ⋯ Changes in the relative abundance of specific bacterial taxa during COPD exacerbations have also been noted although further longitudinal analyses are needed to ascertain the malleability and resilience of this ecological system and its role in the occurrence and frequency of exacerbations. Whether patients with a "frequent exacerbator" phenotype possess specific or greater alterations in their airway microbiome that predispose them to recurrent exacerbations as compared with nonfrequent exacerbators needs to be determined. Although recent data suggest that the presence of bacteria has the potential to influence the host immune response, a key challenge in the next few years will be to continue to move beyond descriptive studies to define the clinical relevance of differences in lung microbiota associated with COPD.
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The human microbiome plays an important and increasingly recognized role in human health. Studies of the microbiome typically use targeted sequencing of the 16S rRNA gene, whole metagenome shotgun sequencing, or other meta-omic technologies to characterize the microbiome's composition, activity, and dynamics. Processing, analyzing, and interpreting these data involve numerous computational tools that aim to filter, cluster, annotate, and quantify the obtained data and ultimately provide an accurate and interpretable profile of the microbiome's taxonomy, functional capacity, and behavior. ⋯ These methods aim to quantify strain-level composition and variation, detect and characterize rare microbiome species, link specific genes to individual taxa, and more accurately characterize the functional capacity and dynamics of the microbiome. These methods and the ability to produce detailed and precise microbiome information are clearly essential for informing microbiome-based personalized therapies. In this review, we survey these methods, highlighting the challenges each method sets out to address and briefly describing methodological approaches.
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Food allergy is a common disease affecting approximately 8% of children and 5% of adults. The prevalence has increased over the last two decades, suggesting an important environmental contribution to susceptibility. Studies have identified mode of birth, pet exposure, and having older siblings as being significant risk modifying factors in the development of food allergy. ⋯ Studies from animal models have clearly shown that the composition of the intestinal microbiota confers susceptibility to food allergy, and that there are organisms such as Clostridia species that are protective in the development of food allergy. Our understanding of microbial regulation of food allergy is in its nascency, but the state of the field supports an important contribution of intestinal microbes to susceptibility. Challenges going forward are to identify commensal-derived microorganisms that could be used therapeutically to prevent or perhaps treat food allergy.
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Gut microbiota changes are important in determining the occurrence and progression of chronic liver disease related to alcohol, nonalcoholic fatty liver disease, and cirrhosis. Specifically, the systemic inflammation, endotoxemia, and the vasodilation that leads to complications such as spontaneous bacterial peritonitis and hepatic encephalopathy could be related to the gut milieu. ⋯ Recent human and animal studies have shown that the relative abundance and the functional changes of microbiota in the stool, colonic mucosa, and saliva have varying consequences on the presence and prognosis of chronic liver disease and cirrhosis. The impact of therapies on the microbiota is slowly being understood and will likely lead to a more targeted approach to gut microbiota modification in chronic liver disease and cirrhosis.