Lung cancer remains one of the deadliest diseases, with current immune-boosting treatments helping only about 20-30 per cent of patients. These therapies work by unleashing the body’s natural defences to attack tumours, but many people don’t respond well.
Now, researchers at the University of Florida Health Cancer Center have uncovered a promising breakthrough. They have discovered a small molecule produced by bacteria in the gut that could significantly improve treatment outcomes.
The molecule, called Bac429, comes from a group of friendly gut bacteria known as Bacteroides. Scientists identified it by studying stool/feces samples from lung cancer patients who responded well to immune therapies and compared them to those who didn’t. In patients who benefitted from treatment, these bacteria were more abundant and they produced higher levels of Bac429.
This compound acts like a natural booster, helping immune cells produce a substance that increases their ability to target and shrink tumours. In experiments with mice engineered to mimic human non-small cell lung cancer (NSCLC), the researchers tested Bac429 alongside standard immune treatments. The results were striking: tumours shrank by up to 50 per cent in treated mice, and the effect even spread to untreated tumours elsewhere in the body. This activity suggests a whole-body immune activation.
Importantly, Bac429 worked without needing to introduce live bacteria into the tumours. It seems to start its helpful effects in the gut, then signals immune cells to travel and fight cancer more effectively.
The molecule’s specific structure, with a unique chemical bond, is key to its power. Similar versions without this feature had inferior performance.
The University of Florida researchers documented their findings in the peer-reviewed science journal Cell Reports Medicine on Dec. 19.
Online now: Microbial-derived immunostimulatory small molecule augments anti-PD-1 therapy in lung cancer https://t.co/lLR3VidV93
— Cell Reports Medicine (@CellRepMed) December 25, 2025
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Findings highlight the importance of gut health
This discovery builds on the growing understanding that our gut bacteria play a big role in overall well-being, including how we respond to cancer treatments. For instance, diets rich in certain carbs might encourage these helpful bacteria to thrive and produce more Bac429.
The team used advanced techniques like separating bacterial products and testing them on immune cells from both mice and humans to validate their findings.
Going forward, the researchers are developing drug versions of Bac429 for human trials, possibly delivered through injections or combined with other therapies.
If successful, it could boost response rates by half, offering new hope for the millions negatively impacted by lung cancer without invasive procedures like fecal transplants.
While more studies are needed to understand exactly how it works and ensure safety, this research highlights the untapped potential of our body’s microbial partners for fighting against disease.
“These findings present exciting avenues for research in bacterial-derived metabolites as precision lead therapeutics,” the authors concluded in their article. “While additional investigation is needed to identify the mechanism behind Bac429 stimulation of cytotoxic CD8+ T cells [cancer-killing immune cells] as well as optimal dosing strategies, this molecular family represents a potentially impactful new treatment in the clinic for deadly later stage NSCLC.”
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