Hundreds of new viruses living inside bacteria within our gut have been discovered in an international study led by Professor Jeremy J. Barr from Monash University's School of Biological Sciences and Associate Professor Sam Forster from Hudson Institute of Medical Research.
These viruses, known as bacteriophages, could eventually be used to reshape the gut microbiome, potentially influencing gut health and the progression of various disease states.
Published in Nature , the study is the first of its kind and uses a large-scale, culture-based approach to isolate and study temperate bacteriophages in the human gut.
The research team worked with 252 bacterial isolates from the human microbiome, which were sourced from the Australian Microbiome Culture Collection (AusMiCC).
These isolates had to be grown in the lab using specialised anaerobic chambers devoid of oxygen, and were then treated with ten diverse compounds, foods, and conditions. Surprisingly, the team found that Stevia, a common plant-based sugar substitute, and compounds released by our own gut cells, were leading activators for gut phages.
"This is a foundational study that changes how we think about and study the viruses within the human gut," said Professor Barr, who was the senior author of the study.
"We found that compounds produced in human gut cells can wake up dormant viruses inside gut bacteria. This could have major implications for gut diseases like inflammatory bowel disease (IBD), where inflammation and cell death are common."
The study also revealed that most gut bacteriophages are dormant, with only a small fraction capable of being activated under the tested conditions.
However, when exposed to human gut cells, the activation rate of these viruses jumped significantly, suggesting that human biology plays an important and direct role in shaping the viral landscape of the gut.
"We've known that the gut is full of viruses, but until now, we didn't have the tools and experimental approaches to study them in the lab," explained Dr Sofia Dahlman , first author on the study. "Our findings suggest that the human host isn't just a passive environment, it's actively influencing viral behaviour."
Using CRISPR-based genetic engineering, the team further identified mutations in viral genes that prevent activation, offering insight into how some gut viruses become permanently dormant. This discovery could inform future therapeutic strategies aimed at manipulating the gut microbiome for health benefits.
The research represents over eight years of collaborative work between Monash University and Hudson Institute of Medical Research, along with several other national and international research teams.
Associate Professor Forster believes that this foundational study will have significant implications for health translation.
"Being able to grow these viruses allows us to understand their function and provides the opportunity to develop microbiome therapeutics for diseases from inflammatory bowel disease to cancers. This technology also provides a capacity to engineer probiotic strains with tailored viral functions," he said.
Professor Barr agreed, saying: "This work lays the groundwork for future applications in synthetic biology, biotechnology, and microbiome therapeutics; it's a major step forward in decoding the viral dark matter of the human gut."
DOI: 10.1038/s41586-025-09614-7
