Investigating the biological and clinical significance of human dysbioses

Abstract

Culture-independent microbiological technologies that interrogate complex microbial populations without prior axenic culture, coupled with high-throughput DNA sequencing, have revolutionized the scale, speed, and economics of microbial ecological studies. Their application to the medical realm has lead to a highly productive merger of clinical, experimental, and environmental microbiology. The functional roles played by members of the human microbiota are being actively explored through experimental manipulation of animal model systems and studies of human populations. In concert, these studies have appreciably expanded our understanding of the composition and dynamics of human-associated microbial communities (microbiota). Of note, several human diseases have been linked to alterations in the composition of resident microbial communities, so-called dysbiosis [1]. However, how changes in microbial communities contribute to disease etiology remains poorly defined. Correlation of microbial composition represents integration of only two datasets (phenotype and microbial composition). This article explores strategies for merging the human microbiome data with multiple additional datasets (e.g. host single nucleotide polymorphisms [SNP] and host gene expression) and for integrating patient-based data with results from experimental animal models to gain deeper understanding of how host-microbe interactions impact disease.

Prevention of Virus-Induced Type 1 Diabetes with Antibiotic Therapy

“…All of the changes detected in at-risk subjects were attributed to Bacteroides, and .20% of the changes within this genus were observed in the Bacteroides ovatus species (13). Whether these changes in the gut microbiome contribute to T1D progression or simply are a consequence of disease remains an open question (19). Other groups have demonstrated that gut bacteria are linked with T1D in the diabetes-prone BioBreeding (BB) rat (20) and NOD mouse (14,21).…”

Evidence of Uncultivated Bacteria in the Adult Female Bladder

“…Bacterial community composition, as revealed by deep 16S sequence analyses, is argued to contribute to diverse human health and disease states (10). While the microbial community structure has been shown to influence susceptibility to infection in models of gastrointestinal disease (2,4,5,34), the application of this concept to the female urinary tract has not been pursued.…”

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

“…Although CRS could be associated with shifts in microbiota and may be associated with decreased bacterial diversity, it is unclear whether there is a causal relationship between these alterations and disease progression or if they are a byproduct of either the pathogenic process or ensuing medical therapies. 448 For instance, antibiotic administration results in a dramatic decrease in richness and diversity of resident bacterial communities, as observed in the gut of healthy subjects and in a study of AECRS. 449,450 Observed alterations in local microbiota in CRS may result from repeated and prolonged medical therapies.…”