Japan researchers identify gut bacteria strain that boosts anticancer drugs

Japan Times

14-07-2025

The gut microbiome, comprising over 100 trillion bacteria in the intestines, is known to play a vital role in human health, affecting the immune system, heart function and weight. Now, researchers at the National Cancer Center Japan say they have discovered how a previously unknown group of gut bacteria can boost the efficacy of a class of anticancer drugs.
In a study published Tuesday in the journal Nature, NCCJ researchers said this bacteria group, which they named YB328, was found to improve the performance of cancer therapies called immune checkpoint inhibitors.
Several such immunotherapy drugs, such as Opdivo and Keytruda, have been launched over the past decade and are used for a broad range of advanced cancers, boosting the long-term survival of some patients. But their response rate is currently at around 20%, meaning they don't work for the majority of people who receive them.
The researchers analyzed stool samples from 50 patients with lung and stomach cancer who underwent checkpoint inhibitor therapies, examining the performance of the drugs for each patient and their gut microbiome. The genomic analysis showed that a group whose therapies worked had higher ratios of bacteria belonging to the Ruminococcaceae family, while those who didn't see improvement after checkpoint inhibitor therapies had higher ratios of other types of bacteria.
The median number of days that patients managed to keep their disease from worsening was 119 for those with high Ruminococcaceae ratios and 38 for those whose Ruminococcaceae ratios were low.
The researchers also isolated the YB328 strain of the Ruminococcaceae family from the patients' feces, then cultured and administered the bacteria to mice. They found that the strain activated dendritic cells, which are immune cells that capture pathogens and cancer cells and instruct other cells to attack them.
Furthermore, the activated dendritic cells were observed to move to lymph tissues and tumor cells, triggering the antitumor response by T cells, a type of white blood cell that helps fight cancer, the researchers said.
'Not only have we succeeded in finding a new group of bacteria that affects the efficacy of anticancer drugs, but we have also made clear how these gut bacteria affect the immune environment of tumors far away from the intestines,' said Hiroyuki Mano, head of the research institute at NCCJ, adding that the researchers see both discoveries as significant.
Immune checkpoint inhibitors are a type of immunotherapy that, instead of attacking cancer cells directly, allow the immune system to recognize and attack cancer cells. The inhibitors block proteins on immune cells that act like 'brakes' on the immune system. The scientists think that adding YB328 to the gut microbiome would improve the chances of immune cells switching off the brakes.
The researchers are working closely with ARC Therapies, an NCCJ spinoff, which is eying a clinical trial of an oral drug based on YB328.
But it will be years before the bacteria become available as a medication, as many questions remain unresolved, such as what component of the bacteria is responsible for the boosted T cell response and the suitable doses for humans, Mano said.