For individuals unresponsive to conventional cancer therapies, fecal transplants from patients who have successfully undergone treatment could significantly enhance recovery odds. Modifying the gut microbiome impacts the immune response and has shown potential in stabilizing tumors during initial studies involving kidney cancer patients.

Fecal microbiota transplantation (FMT) is a safe procedure where a stool sample from one individual is transferred into another’s intestine to improve microbiome diversity. Initially approved to tackle recurring antibiotic-resistant Clostridioides difficile infections, FMT is on the rise in both the UK and US, and it has shown promise in conditions like irritable bowel syndrome.

While immunotherapy drugs, such as checkpoint inhibitors, enhance immune system functions to combat cancer cells, they may not be universally effective. Previous studies suggest that FMT from responding individuals could provide benefits for non-responders. “The microbiome significantly influences host immunity; thus, modifying it may enhance immune responses and facilitate cancer cell destruction,” states Gianluca Ianilo from the Catholic University of the Sacred Heart in Rome, Italy.

Prior research predominantly examined melanoma, a specific skin cancer, without comparing FMT effects to a placebo. To mitigate these gaps, Ianilo and colleagues enlisted 45 adults with kidney cancer who had commenced dual therapy with the checkpoint inhibitor pembrolizumab and axitinib—a medication obstructing tumor blood supply—within the last two months.

Participants were randomly split into two groups: one receiving FMT from a male donor whose cancer remitted post-checkpoint inhibitors, and the other receiving saline, both administered through a small tube rectally.

Following the initial transplant, most participants were given two additional doses (FMT or saline) three and six months later, but this time in oral pill form.

In the FMT cohort, participants maintained stable cancer status for an average of two years following the first transplant, contrasting with just nine months in the placebo group. Moreover, over half of those in the FMT group experienced tumor reduction, compared to approximately one-third in the placebo group.

“This provides robust evidence indicating that gut microbiome manipulation can significantly affect immunotherapy outcomes,” claims Hassan Zaroor from the University of Pittsburgh, Pennsylvania.

While the exact mechanism of FMT’s efficacy remains unclear, stool sample analyses taken before and after FMT indicate that FMT may introduce beneficial gut bacteria like Blautia wechslerae, which produce short-chain fatty acids that promote anti-cancer immune responses.

Additionally, FMT appeared to adjust the bacterial composition in recipients’ guts. For instance, it diminished levels of harmful strains like Escherichia coli, which trigger inflammation, while boosting beneficial bacteria like Ruminococcus bromii, known for enhancing growth of other beneficial bacteria that produce short-chain fatty acids.

This finding aligns with another recent study indicating that FMT can significantly enhance the effectiveness of checkpoint inhibitors in patients with non-small cell lung cancer compared to immunotherapy alone.

These trials suggest that FMT may also prove effective against additional tumor types responsive to checkpoint inhibitors, including those affecting the bladder and head and neck, although larger randomized controlled trials are necessary to validate these findings, according to Elkrief.

Future research must determine which specific bacterial strains confer benefits, potentially enabling the development of synthetic microbial preparations for widespread cancer treatments, Ianilo emphasizes.