Topological distortion and reorganized modular structure of gut microbial co-occurrence networks in inflammatory bowel disease.

Steven N Baldassano,Danielle S Bassett

doi:10.1038/srep26087

Abstract

The gut microbiome plays a key role in human health, and alterations of the normal gut flora are associated with a variety of distinct disease states. Yet, the natural dependencies between microbes in healthy and diseased individuals remain far from understood. Here we use a network-based approach to characterize microbial co-occurrence in individuals with inflammatory bowel disease (IBD) and healthy (non-IBD control) individuals. We find that microbial networks in patients with IBD differ in both global structure and local connectivity patterns. While a “core” microbiome is preserved, network topology of other densely interconnected microbe modules is distorted, with potent inflammation-mediating organisms assuming roles as integrative and highly connected inter-modular hubs. We show that while both networks display a rich-club organization, in which a small set of microbes commonly co-occur, the healthy network is more easily disrupted by elimination of a small number of key species. Further investigation of network alterations in disease might offer mechanistic insights into the specific pathogens responsible for microbiome-mediated inflammation in IBD.

Highlights

Previous studies have focused on alterations in abundance levels of microbial species in disease, with less consideration of changes in larger-scale interspecies relationships
We assess the organization of microbial co-occurrence networks with a battery of statistics drawn from the toolbox of techniques developed in the field of network science
Each assessment addresses a different scale of organization within the networks

Summary

Introduction

Previous studies have focused on alterations in abundance levels of microbial species in disease, with less consideration of changes in larger-scale interspecies relationships. We measure the robustness of each network to simulated attacks in which species are removed to assess their topological role This simulation technique enables us to compare the predicted fragilities of the healthy and diseased networks and to gain insight into the possible effects of broad-spectrum antibiotic use. This hierarchical, graph-based analysis of co-occurrence networks in IBD provides a unique perspective for the identification of potential pathogenic species, comparison of microbial communities, and assessment of global network fitness

Methods

Results

Discussion

Conclusion