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New research shows antibiotics upset the gut microbiome, allowing drug-resistant pathogens to spread, but restoring microbial balance could stop them.
Researchers from the Department of Life Sciences have uncovered how antibiotic treatment alters the gut environment in ways that promote colonisation by vancomycin-resistant enterococci (VRE) – pathogens responsible for serious, hard-to-treat infections. The findings, published in Nature Communications, could help inform the design of next-generation microbiome therapeutics aimed at preventing such infections before they begin.

VRE are a major cause of hospital-acquired infections, including bloodstream infections, urinary tract infections and endocarditis. The gut serves as a key reservoir for VRE, with colonisation often preceding invasive disease.

The research team, led by Dr Julie McDonald from Imperial’s Department of Life Sciences and Centre for Bacterial Resistance Biology, found that antibiotics can unintentionally make the gut a more hospitable environment for opportunistic pathogens by damaging the protective community of microbes – the gut microbiota – that normally keeps harmful bacteria in check.

How antibiotics open the door to superbugs

While essential to modern medicine, antibiotics also kill beneficial gut bacteria. First author Dr Olivia King said: ‘It was striking how antibiotic treatment reshapes the gut in a manner which unintentionally favours pathogens like VRE – it highlights the delicate balance between using antibiotics to treat infection and the risk of fuelling resistance’.

This disruption has two major consequences: it increases the availability of nutrients in the gut that VRE can exploit while also decreasing the production of protective microbial compounds, called metabolites, that normally suppress VRE growth.

In a healthy gut, beneficial microbes compete for nutrients and produce metabolites called short-chain fatty acids that act like natural antibiotics to restrict VRE growth. After antibiotic treatment, these defences are weakened or lost. While individual metabolites had limited effects, combinations of these short-chain fatty acids could completely inhibit VRE growth under lab conditions.

The team also showed that antibiotics killed beneficial bacteria from the gut microbiota that normally deplete a wide range of nutrients. They found that these nutrients became more abundant during antibiotic treatment, and VRE used these nutrients as food sources to support their growth.
Finally, the team discovered that VRE occupied distinct microenvironments in the gut, separate from those used by other antibiotic-resistant pathogens like carbapenem-resistant Enterobacteriaceae (CRE) – suggesting that tailored therapeutic strategies may be needed to target specific pathogens.

Towards new microbiome-based therapies

The findings could pave the way for new treatments that work with the microbiome to prevent infection. These may include probiotic cocktails that restore protective gut bacteria and deplete nutrients used by VRE and metabolite-based supplements administered alongside antibiotics to suppress harmful bacteria.
Dr McDonald said: ‘Our findings lay the foundation for the development of novel targeted microbiome therapeutics that could be used to restore a healthy gut environment that restricts VRE growth’. ‘This could remove a major reservoir for VRE, preventing the development of difficult-to-treat infections.’
The team collaborated with researchers across Imperial, including Dr Thomas Clarke (Department of Infectious Disease), Dr Benjamin Mullish, and Professor Julian Marchesi (Department of Metabolism, Digestion and Reproduction), who contributed to key experiments such as the mouse model, human faecal sample collection, and sequencing work.