Changes to gut bacteria found to improve chemotherapy drug delivery to tumours

Researchers have found that a short course of antibiotics can reshape the gut microbiome to help nanoparticle-based chemotherapy circulate for longer and reach tumours more effectively

A study led by scientists at The University of Texas MD Anderson Cancer Center, Houston, Texas, USA, has identified a way to reshape the gut microbiome that can enhance the delivery of certain chemotherapies to tumours, offering a potential strategy to make nanoparticle-based cancer drugs more effective.

The study was led by Dr. Betty Kim, professor in the Department of Neurosurgery, Dr. Wen Jiang, associate professor in the Department of Radiation Oncology, and Dr. Jennifer Wargo, professor in the Departments of Surgical Oncology and Genomic Medicine. Kim and Wargo are both core members of the James P. Allison Institute, and the research was carried out as a collaborative project through the Platform for Innovative Microbiome and Translational Research (PRIME-TR) based at MD Anderson.

In preclinical models, reshaping gut bacteria with a short course of antibiotics roughly doubled the length of time nanoparticle-based chemotherapy remained in circulation, increasing how much of the drug accumulated in tumours and improving survival across several cancer types. Notably, the effect was driven by the microbiome itself rather than the immune system, a finding that suggests microbiome-directed approaches could one day be used to improve delivery in this class of chemotherapy.

“For decades, scientists have tried to address how aggressively the liver filters out nanomedicine by redesigning the drugs themselves. Our research shows that the host's biology – specifically the gut microbiome – is just as important as the particle design,” Jiang said.

“This is the first study to demonstrate that the gut microbiome can directly impact chemotherapy, opening up an entirely new strategy for boosting cancer treatment,” he added.

Nanoparticle-based chemotherapy – drugs packaged inside microscopic carriers such as liposomes or albumin particles – is used to treat a range of cancers, including breast, ovarian and pancreatic. However, most of the therapy never reaches the tumour, because immune cells in the liver – known as Kupffer cells – aggressively clear the drug particles from the body.

Gut bacteria send chemical signals to those liver cells through bile acids, natural chemicals produced when gut bacteria process bile. When researchers administered the commonly used antibiotic metronidazole to selectively reduce certain gut bacteria, bile acid levels dropped, causing the Kupffer cells to shift into a 'quiet' state.

As a result, the Kupffer cells cleared fewer of the nanomedicine particles, allowing for extended circulation and increased accumulation in the tumour. This translated into significantly slowed tumour growth and prolonged survival in preclinical models of four cancer types: colon, breast, melanoma and pancreatic.

To determine whether the microbiome itself was responsible, rather than residual antibiotic, the researchers carried out faecal microbiota transplantation (FMT), transferring gut microbial communities from antibiotic-treated donors into germ-free recipient models. Testing confirmed that the transferred material carried no detectable antibiotic, yet these recipients still showed the same improved tumour delivery seen in the original antibiotic-treated group.

Earlier research from the Wargo Laboratory and PRIME-TR has shown that the gut microbiome can improve the effectiveness of immunotherapy by reinvigorating the immune system to attack cancer cells. These latest results confirm that the beneficial effect is encoded within the microbiome and can be transferred between hosts.

The study is the first to show that the gut microbiome can directly improve chemotherapy by changing how drugs are physically distributed around the body, a finding that positions microbiome-targeted strategies as potential future approaches for enhancing nanoparticle cancer therapy.

In this study, FMT served to demonstrate that the microbiome drives the effect and can carry it between hosts, rather than as a proposed cancer therapy in its own right. The findings nonetheless present several promising avenues for clinical translation. Metronidazole has already been approved by the US Food and Drug Administration and has a well-established safety profile which makes short-course administration alongside nanoparticle-based chemotherapy a tractable strategy for near-term clinical investigation.

Rather than relying on prolonged antibiotic exposure that broadly depletes the gut microbial community, future research could explore how to selectively engineer a beneficial microbiome state through short-course antibiotic modulation, defined microbial consortia or bile acid-directed therapies that reproduce the effect. The study also suggests that gut microbiome profiles and bile acid signatures could one day serve as biomarkers to predict which patients will respond best to nanomedicine, and which might benefit from microbiome-modulating co-treatment beforehand.

“Hepatic clearance is not a fixed physiological constraint but a dynamic state that can be modulated through the microbiome,” Wargo said.

“By understanding how the microbiome shapes drug delivery, we can begin thinking about chemotherapy not just as a drug-tumour interaction, but as a drug-microbiome-host interaction, which changes how we might design treatment plans for patients in the future,” she explained.

For further reading please visit: 10.1038/s41563-026-02690-8