Active Infection & Immunity Digestion, Kidneys & Other Organs

Harnessing nutrient metabolism by the gut microbiota to restrict the intestinal colonisation with multidrug-resistant pathogens

Funder Wellcome Charity-funded
Recipient organisation Imperial College London
Funding £2.7M
Period Apr 2024 — Apr 2032

In plain English

AI plain-English summary

The gut of a hospital patient on antibiotics becomes a breeding ground for drug-resistant bacteria, and this project aims to starve those pathogens out by manipulating their food supply. Multidrug-resistant pathogens like *C. difficile* and drug-resistant *E. coli* first colonise the intestine, then spread to cause bloodstream or urinary tract infections that are difficult or impossible to treat. Antibiotics wipe out the protective gut microbes that normally compete for nutrients and produce inhibitory chemicals, leaving empty niches that resistant pathogens exploit. Current methods to clear this intestinal reservoir are limited. The researchers plan to map exactly which nutrients each pathogen and beneficial microbe consumes, and which metabolites inhibit pathogen growth. They will then design synthetic bacterial consortia—custom blends of harmless microbes—that outcompete the pathogens for specific nutrients or produce targeted inhibitors. If successful, this would provide a precision alternative to faecal transplants, allowing clinicians to predictably clear resistant bacteria from a patient’s gut before they cause invasive infections. The work is fundamental science with a clear translational path: understanding the metabolic rules of gut colonisation to build microbiome-based therapies.

View original technical description
The intestine is the primary colonisation site for multidrug-resistant (MDR) pathogens and acts as a reservoir of pathogens that seed difficult-to-treat invasive infections. Methods to remove the intestinal reservoir of MDR pathogens are urgently needed. The healthy gut microbiota protects against pathogen colonisation via colonisation resistance (e.g. nutrient competition and metabolite inhibition). However, antibiotics disrupt colonisation resistance and promote MDR pathogen colonisation. Our aim is to predict and restrict MDR pathogen intestinal colonisation by manipulating the nutrient- and metabolite-defined niches occupied by MDR pathogens. Our objectives are: (1) to define the nutrient utilisation abilities and metabolite inhibition susceptibilities of MDR pathogens and gut commensals, (2) to investigate how MDR pathogens occupy nutrient-enriched and metabolite-depleted intestinal niches; (3) to predict the impact of excluding microbial functional groups on MDR pathogen colonisation, and (4) to manipulate nutrient metabolism by the gut microbiota to protect against MDR pathogen colonisation. This proposal will deliver a significant shift in the field by establishing that we can predict and control MDR pathogen colonisation within the intestine by modifying nutrient- and metabolite-defined intestinal niches using synthetic bacterial consortia. This project will lay the groundwork to design effective microbiome therapeutics to prevent or restrict MDR pathogen intestinal colonisation.

View the original record at the funder ↗

Researchers

Julie Anne Kathryn McDonald (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Nutrient competition and metabolite production by the gut microbiota to reduce carbapenem-resistant Enterobacteriaceae growth in the human intestine
Decoding metabolic niche to engineer microbiome communities
Investigating the role of gut microbiota-mediated colonisation resistance against carbapenem-resistant Enterobacteriaceae
Gut-on-chip models for clearing pathogens with the competitive abilities of gut strains
The ecology and metabolome of microbial communities

Original classification

Career Development Award

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.