Bacteria in stools could be an unexpected weapon in the fight against cancer
LEWIS HOUGHTON/SCIENCE PHOTO LIBRARY
For people not responding to a type of cancer treatment, a faecal transplant from someone who had success with the drug could boost their odds. Altering the gut microbiome has knock-on effects on the immune system, which seemed to help stabilise tumours in a small trial of people with kidney cancer.
Faecal microbiota transplantation (FMT) is a safe procedure that involves transferring stool samples from one person to the gut of another, with the hope it will improve their microbiome. It is approved for treating recurrent antibiotic-resistant Clostridioides difficile infections in the UK and the US, and has shown promise for other conditions, such as irritable bowel syndrome.
When treating cancer, immunotherapy drugs known as checkpoint inhibitors can be effective by helping the immune system destroy cancer cells, but they don’t work for everyone. Prior studies suggest that a FMT from people who respond to these drugs to the guts of those who don’t can be beneficial. “The microbiome is a strong regulator of host immunity, so we hypothesise that altering it can boost immunity to help kill cancer,” says Gianluca Ianiro at the Catholic University of the Sacred Heart in Rome, Italy.
But such studies typically focused on melanoma, a type of skin cancer, and didn’t compare the effects of faecal transplants to a placebo. To address these limitations, Ianiro and his colleagues recruited 45 adults with kidney cancer who had started taking the checkpoint inhibitor pembrolizumab plus axitinib, a drug that disrupts tumours’ blood supply, within the past two months.
They then randomly assigned the participants to receive either a stool transplant – collected from a man who went into remission for cancer after receiving checkpoint inhibitors – or a saline solution, both delivered into the large intestine via a small tube through the anus.
At three and six months after the first transplant, most of the participants then took two further doses of their assigned treatment – either a FMT or saline solution – but this time in the form of oral pills.
Within the FMT group, the participants’ cancer was stable for two years, on average, after their first transplant, compared with nine months in the placebo group. What’s more, just over half of those in the FMT group saw their tumours shrink, compared with only around a third in the placebo group.
“This meaningfully strengthens the evidence that the gut microbiome can be therapeutically manipulated to influence immunotherapy outcomes,” says Hassane Zarour at the University of Pittsburgh in Pennsylvania.
Exactly how the faecal transplantation may have helped is unclear, but analysis of stool samples collected from the participants before and after the FMT suggests that it introduced a species of gut bacteria called Blautia wexlerae, which produces short-chain fatty acids known to promote anti-cancer immune cells.
The faecal transplants also seemed to alter levels of bacteria already present in the recipients’ guts. For instance, they reduced levels of a strain of Escherichia coli that promotes harmful inflammation, and raised levels of Ruminoccocus bromii, which encourages the growth of other bacteria that produce short-chain fatty acids.
The findings chime with another small trial out this week that showed FMT can substantially boost the effects of checkpoint inhibitors in people with non-small cell lung cancer, compared to those on the immunotherapy alone.
These trials suggest that FMT could also work against other tumour types that respond to checkpoint inhibitors – such as those affecting the bladder and head and neck – but large, randomised controlled trials are needed to confirm this, says Elkrief.
Further research also needs to establish exactly which bacteria strains within faeces are beneficial, which could enable the creation of artificial microbial samples that can be produced for cancer treatment on a large scale, says Ianiro.
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