CoRe Defense: fortifying the resident gut microbiota’s colonization resistance to combat intestinal bacterial infections.

Introduction

Currently, we rely on antibiotics to combat potentially life-threatening gastrointestinal (GI) bacterial infections. However, the susceptibility to infection and the severity of symptoms can vary significantly among individuals exposed to the same pathogen. If we could unravel the factors responsible for differences in infection susceptibility, we could formulate strategies to reduce the incidence of symptomatic infections, ultimately saving lives and reducing the need for antibiotics.

Research Perspectives

Traditionally, researchers have approached this puzzle from two main perspectives:

1. A human-centered view, delving into the intricacies of the host immune system.
2. A pathogen-centered view, scrutinizing variations in bacterial strains.

Proposed Approach

With CoRe defense, I advocate for a paradigm shift by adopting a microbiota-centered perspective. This approach is grounded in the concept of colonization resistance, the mechanism whereby the intestinal microbiota protects itself against incursion by new microorganisms.

Challenges in Current Methods

Despite their tremendous potential to prevent and treat bacterial infections, microbial alternatives to antibiotics are still spread thin as we currently lack adequate methods to select potential candidates.

Objectives

My aim is to develop a method for the selection of personalized bacterial consortia capable of preventing Campylobacteriosis. I will do so by:

1. Investigating its ecological niche and competitors through metabolic modelling.
2. Screening for growth-reducing bacterial strains or consortia using a newly developed in vitro co-culturing platform.
3. Testing colonization resistance predictions of a simple model based on these in silico and in vitro results in human-microbiome associated mice.

Expected Outcomes

By investigating the protective function of the microbiota, I will generate ground-breaking findings that will transform our understanding of the factors governing bacterial infection susceptibility. It will usher in an era where we view bacteria not only as the problem but also as part of the solution.