Origin, evolution and function of bacterial extracellular vesicles in the human host-gut microbiome system

Introduction

Bacterial extracellular vesicles (BEVs) are small membrane vesicles secreted by a diverse range of bacteria that act as bioactive nanocarriers of a high diversity of proteins, lipids, and nucleic acids. BEVs have mostly been studied in pathogenic bacterial models, owing to their causal role in pathogenicity.

Background

Compared to other microbial features, such as taxa, genes, or metabolites, BEVs secreted by the large diversity of commensal bacterial species of the human gut microbiota have received little attention so far. This leaves their influence upon gut microbial ecology and human health almost entirely unknown.

Hypothesis

We hypothesize that gut BEVs and their molecular cargos (i.e., the gut bacterial vesiculome) play critical roles in bacteria-bacteria and host-microbiome interactions, and in shaping phenotypes of host-microbiome systems.

Project Objectives

Our project will enable a comprehensive profiling of BEV molecular diversity across a large number of gut bacterial taxa, and a functional analysis of their impact on inter-species and inter-kingdom interactions. We intend to tackle these objectives through three aims:

1. Characterize the origin, diversity, and evolution of the human gut bacterial vesiculome.
2. Investigate the role of BEVs in promoting horizontal gene transfers among bacterial species in the gut microbiome.
3. Investigate the role of BEVs on bacteria-bacteria and host-bacteria interactions.

Methodology

We will tackle each of these aims from three diversity perspectives:

• Investigating multiple bacterial species.
• Including geographically-distinct healthy human populations.
• Comparing healthy vs. disease.

Expected Outcomes

The project will expand our basic understanding of the evolution and function of bacterial vesiculation. It will also generate the first atlas of BEV profiles across gut bacterial taxa and host cohorts, providing key resources to mine for vesicular characteristics and functions that have translational potential for biomedicine.