Gut Bacterial Metabolite Boosts Immune Checkpoint Therapy Efficacy in Lung Cancer: Study Shows - Video

80% of lung cancer patients fail immunotherapy, but UF researchers found a gut bacteria molecule that could DOUBLE response rates.

UF Health Cancer Institute scientists discovered Bac429, a natural compound from gut bacteria that slashed lung tumor growth by 50% when paired with immunotherapy in mice. Published in Cell Reports Medicine, Rachel Newsome, Ph.D., and Christian Jobin's team's breakthrough, now drug-ready for humans, promises to transform the deadliest cancer's weakest treatment.

Immune checkpoint inhibitors "release the brakes on immune cells to attack cancer, but only 20% of patients respond across all cancers. Lung cancer fares worst. The gut microbiome (trillions of bacteria) mysteriously determines who benefits—responders have different bacteria than non-responders.

How they cracked the microbiome code:

1. Human feces → mice: Transplant stool from immunotherapy responders into tumor-bearing mice. Non-responders suddenly responded.

2. From 180+ strains, isolated 6 superstar bacteria that boosted immunotherapy alone.

3. Pinpointed Bac429 metabolite that these bacteria produce. Injected directly into lung tumors = 50% less growth post-immunotherapy.

"Bac429 works like the six bacteria but as a simple drug—no messy fecal transplants needed." Christian Jobin: "We engineered a pipeline harvesting microbiome's therapeutic gold."

Bac429 likely activates gut immune cells that migrate to tumors, supercharging immunotherapy. Mouse tumors shrank dramatically even in "non-responder" models.

Drug derivatives in development. Could pair with checkpoint inhibitors to boost 20% → 40-50% response rates.

No surgery/chemo added—just pills enhancing immunotherapy's natural power. With microbiome science exploding, Bac429 proves gut bacteria hold cancer's secret weapon. Human trials imminent could slash lung cancer deaths while expanding immunotherapy's reach from 1-in-5 to majority of patients.

This isn't just a drug—it's microbiome medicine decoding why some immune systems fight cancer while others sleep. One bacteria byproduct could rewrite oncology.

REFERENCE: Newsome, R. C., et al. (2025). Microbial-derived immunostimulatory small molecule augments anti-PD-1 therapy in lung cancer. Cell Reports Medicine. doi: 10.1016/j.xcrm.2025.102519. https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00592-0