Completed Infection & Immunity Plants, Animals & Ecology

Understanding and engineering complex microbial communities

In plain English

AI plain-English summary

The human gut’s natural microbial shield against dangerous bacteria often collapses under antibiotic treatment, leaving patients vulnerable to infections like Salmonella. This project aims to design synthetic microbial communities that remain stable and protective even when antibiotics are present. The problem is that the gut’s ecosystem is staggeringly complex—dozens of bacterial species interact, compete, and evolve in ways that make their collective behaviour nearly impossible to predict. Current probiotics are too simple to fill the gap. This research will first build mathematical theory and computational tools to model these interactions, then test those models by engineering lab-grown gut communities that resist both antibiotics and pathogen invasion. Finally, the team will move into live mice to see whether the engineered communities can block Salmonella infection in a real body. If successful, this work could lead to a new class of “designer” probiotic therapies—microbial cocktails tailored to restore colonisation resistance after antibiotic courses, reducing hospital-acquired infections and the need for further antibiotics. The project is fundamentally curiosity-driven, tackling the deep challenge of predicting complex biological systems. Past fundamental work on microbial ecology has already transformed wastewater treatment and agriculture; a similar understanding of the gut could eventually reshape how we manage infection risk in vulnerable patients.

View original technical description
The human microbiota provides protection against pathogens via colonisation resistance. However, this resistance is not guaranteed, especially in the face of antibiotic treatment that suppresses the microbiota. My goal is to engineer communities for robustness to both antibiotics and pathogens. The challenge is that communities are complex systems containing many interacting and evolving species, making them challenging to predict and understand. Aim 1. Develop theory and analysis tools for complex microbial communities We will develop complex systems theory and quantitative tools to meet the challenges of understanding and engineering diverse communities. Aim 2. Apply theory to in-vitro gut communities We will apply our theory and test our ability to design gut communities that are robust to either antibiotic treatment, colonisation by the enteric pathogen Salmonella Typhimurium, or both. We will then study community and pathogen evolution: can a pathogen easily resist a probiotic community? Will the community evolve in response? Aim 3. Apply theory to S. Typhimurium pathogenesis We will study S. Typhimurium in gnotobiotic mice and test our ability to design robust communities in vivo. We will ask if S. Typhimurium can overcome in vivo colonisation resistance.

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Researchers

Kevin Foster (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Innovative experimental approaches to determine how the human microbiota prevents Salmonella Typhimurium infections
The Evolution of Competition and Cooperation: how polymorphisms in microbial populations optimise virulence and mediate drug resistance
Antimicrobial resistance mechanisms in the presence of sub-inhibitory antibiotics and the microbiome
Bacterial competition in colonic crypts
Ecology and evolution of commensal and pathogen species within the gut microbiota

Original classification

Investigator Award in Science

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