Bifidobacteria as a model system for host-microbe interaction

Our bodies are home to a staggering collection of microbes with the human gut contains up to 2 kilograms of microbial mass.

In healthy individuals the interplay between the immune system and the microbiota prevents tissue damaging inflammatory responses to commensal species of bacteria while permitting immune responses against infectious microbes.

Changes in the gut microbiome have been linked to perturbation of immune function and several inflammatory gut disorders.

Conversely, commensal microorganisms with purported health promoting effects (probiotics) have been implicated as potential therapeutics for several ailments with over 1,300 registered clinical trials using probiotics. Bifidobacteria, a Gram-positive commensal accounts for 475 of these trials.

Bifidobacteria colonise the gastrointestinal tract immediately after birth and affect the maturation of the host’s immune system.

Despite the impact of microbes on our health and the large number of clinical trials underway, our current knowledge of the impact of the microbiota, including probiotics, on health is based almost exclusively on descriptive and correlative studies with a need for studies focused on causality and mechanism.

The central goal of this project is to understand the mechanisms by which Bifidobacterium breve induces an anti-inflammatory and anti-microbial state in host immune cells and to determine if this can be replicated using a synthetic biology approach.

The ability of a range of commensals to elicit immune modulatory responses will also be studied to identify shared mechanisms of host-microbe dialogue across bacterial species.

A thorough understanding of host-microbe interactions that lead to a tolerogenic, anti-inflammatory, and anti-microbial phenotype will aid in the development of novel microbiome-based treatments while the ability to replicate these effects using synthetic biology will establish a basis for novel immune based therapies.