Associated organisationsEth Hoenggerberg · Imperial College London · University of Liverpool · University of TubingenEurope PMC affiliations are not treated as award recipients or mapped locations.
Funding£4.8M
PeriodNov 2025 — Nov 2031
In plain English
AI plain-English summary
The trillions of bacteria living in a healthy human gut can block Salmonella infections, but no one knows why some people’s microbial defences work better than others. This project tackles that gap by building on a unique clinical study where volunteers were deliberately infected with *Salmonella* Typhimurium. Researchers will take stool samples from those volunteers—collected before infection—and transplant them into mice and lab fermenters to recreate the varying levels of protection seen in humans. By tracking how different *Salmonella* strains grow in these models and using multi-omics to analyse nutrient use by resident *E. coli* and other bacteria, they aim to pinpoint the specific microbial traits that determine colonisation resistance. If successful, the work could reveal whether a “universal” protective gut microbiota exists—one that blocks multiple *Salmonella* strains. The team will share the resulting bacterial communities and genome sequences openly, enabling other scientists to design microbiome-based preventative medicines. This is fundamental science: it asks how a complex ecosystem inside us works, with no immediate product in hand. But understanding the rules of microbial protection could eventually lead to probiotic treatments or dietary interventions that strengthen gut defences against diarrhoeal disease.
View original technical description
The gastrointestinal microbiota protects humans from many infections. It remains unknown why levels of “colonisation-resistance” vary from person-to- person. We will focus on S.Typhimurium diarrhoea, building on the unique Wellcome-funded CHANTS S.Typhimurium-human-challenge clinical study to close this knowledge gap.We will create a unique set of human-microbiota models using mice and fermenters. By combining pre-infection CHANTS stool samples with matched data on gut-colonisation by gastroenteritis-associated and bloodstream-associated S. Typhimurium strains, we aim to replicate colonisation-resistance seen in volunteers. We will measure Salmonella infection-kinetics and use multi-omics to probe mechanisms and investigate effects of dietary-composition on colonisation-resistance. Our transformative models will allow colonisation-resistance mechanisms of the human gut microbiota to be studied for first time. We will address critical unanswered questions regarding how the human gut microbiota prevents S.Typhimurium infections: 1) Do the nutrient-utilisation patterns of resident E.coli or other microbiota families determine the level of colonisation resistance?2) Can we identify or create gut microbiotas which universally-protect against a whole range of S.Typhimurium strains with distinct colonisation properties?We will share our microbiota-communities and individual genome-sequence microbiota strains with scientists worldwide to help transform understanding of how human microbiota prevents Salmonella infections, and enable the rational design of microbiome-based preventative medicines.
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