Defining Dysbiosis for a Cluster of Chronic Diseases

Lamont J Wilkins,Manoj Monga,Aaron W Miller

doi:10.1038/s41598-019-49452-y

Abstract

The prevalence of many chronic diseases has increased over the last decades. It has been postulated that dysbiosis driven by environmental factors such as antibiotic use is shifting the microbiome in ways that increase inflammation and the onset of chronic disease. Dysbiosis can be defined through the loss or gain of bacteria that either promote health or disease, respectively. Here we use multiple independent datasets to determine the nature of dysbiosis for a cluster of chronic diseases that includes urinary stone disease (USD), obesity, diabetes, cardiovascular disease, and kidney disease, which often exist as co-morbidities. For all disease states, individuals exhibited a statistically significant association with antibiotics in the last year compared to healthy counterparts. There was also a statistically significant association between antibiotic use and gut microbiota composition. Furthermore, each disease state was associated with a loss of microbial diversity in the gut. Three genera, Bacteroides, Prevotella, and Ruminococcus, were the most common dysbiotic taxa in terms of being enriched or depleted in disease populations and was driven in part by the diversity of operational taxonomic units (OTUs) within these genera. Results of the cross-sectional analysis suggest that antibiotic-driven loss of microbial diversity may increase the risk for chronic disease. However, longitudinal studies are needed to confirm the causative effect of diversity loss for chronic disease risk.

Highlights

Many chronic diseases are on a trend of increasing prevalence
Despite the limitations of microbiome studies, many clinical studies use the differential abundance of operational taxonomic units (OTUs) between healthy and disease populations at a single time-point to determine if dysbiosis contributes to the disease, which can lead to erroneous results when it comes to the nature of dysbiosis and microbial taxa involved
Sequences from the stool and associated sample metadata were drawn from the April 26th, 2017 version of American Gut Project data (AGP), which has an extensive list of metadata that includes antibiotic history and the presence or absence of several disease states[41]

Summary

Introduction

Many chronic diseases are on a trend of increasing prevalence. Cardiovascular disease, obesity, diabetes, urinary stone disease (USD), asthma, and inflammatory bowel disease (IBD) are all on the rise, among others[1,2,3,4,5,6]. We quantified the use of antibiotics in disease populations compared to healthy controls, which can lead to a loss in microbial diversity relevant to disease processes[33,34,35,36,37,38,39,40], quantified metrics of loss or gain of microbiota diversity associated with each disease state relative to stochastically defined populations, determined the similarities and differences in microbial taxa enriched and depleted in disease populations, and determined which of these taxa were differentially abundant more than expected given their genus-level diversity in samples These diseases often exist as comorbidities in patients and have all been linked to the microbiome to some degree. We hypothesize that if the diseases in question are driven in part by dysbiosis, that there will be common metrics of dysbiosis that include antibiotic use, loss or gain of microbial diversity, and microbial taxa associated with disease

Methods

Results

Conclusion