For individuals whose cancer does not respond to standard treatments, a faecal transplant from a donor who achieved success with medication could potentially improve their outcomes. Modifications to the gut microbiome have cascading effects on the immune system, and these seem to have aided in stabilizing tumors during a small trial involving kidney cancer patients.
Faecal microbiota transplantation (FMT) is recognized as a safe procedure. It involves the transfer of stool samples from one individual to the digestive tract of another with the goal of improving their microbial composition. This treatment is already approved in the UK and the US for managing recurrent Clostridioides difficile infections that are resistant to antibiotics. Furthermore, it has demonstrated potential benefits for other conditions, such as irritable bowel syndrome.
Investigating FMT’s Role in Cancer Therapy
In cancer treatment, a class of immunotherapy drugs called checkpoint inhibitors can be effective by enabling the immune system to target and eliminate cancer cells. However, their efficacy is not universal. Previous research has suggested that transferring faecal matter from individuals who respond well to these drugs to the guts of those who do not can yield positive results. “The microbiome is a powerful regulator of host immunity, thus we hypothesize that altering it can enhance immunity to aid in cancer eradication,” stated Gianluca Ianiro from the Catholic University of the Sacred Heart in Rome, Italy.
Prior studies, however, primarily concentrated on melanoma, a type of skin cancer. Crucially, they did not compare the effects of faecal transplants against a placebo. To address these shortcomings, Ianiro and his research team enlisted 45 adult participants diagnosed with kidney cancer. These individuals had recently commenced treatment with pembrolizumab, a checkpoint inhibitor, in combination with axitinib, a drug designed to disrupt tumor blood supply, within the preceding two months.
The participants were then randomly assigned to one of two groups. One group received a stool transplant, sourced from a male donor who had achieved cancer remission after undergoing checkpoint inhibitor treatment. The other group received a saline solution. Both treatments were administered directly into the large intestine using a small tube inserted through the anus.
Treatment Regimen and Observed Outcomes
At the three-month and six-month marks following their initial transplant, the majority of participants received two additional doses of their assigned treatment. These subsequent doses were administered orally in the form of pills, rather than through direct intestinal transfer. This approach applied to both the FMT group and the placebo group.
A significant difference emerged in the FMT group. On average, participants maintained stable cancer conditions for two years subsequent to their first transplant. This contrasts sharply with the placebo group, where cancer remained stable for an average of nine months. Furthermore, the study indicated that just over half of the patients in the FMT group experienced a reduction in tumor size. In comparison, only approximately one-third of those in the placebo group achieved similar results.
Hassane Zarour, affiliated with the University of Pittsburgh in Pennsylvania, commented on these findings, stating, “This meaningfully strengthens the evidence that the gut microbiome can be therapeutically manipulated to influence immunotherapy outcomes.”
Potential Mechanisms and Further Implications
The precise mechanisms by which faecal transplantation may have contributed to improved outcomes remain under investigation. However, an analysis of stool samples collected from participants both before and after the FMT revealed the introduction of a specific gut bacterium species, Blautia wexlerae. This bacterium is known to produce short-chain fatty acids, which are recognized for their role in promoting anti-cancer immune responses.
The faecal transplants also appeared to influence the existing bacterial populations within the recipients’ guts. Specifically, they led to a decrease in the levels of a particular strain of Escherichia coli, known to contribute to detrimental inflammation. Concurrently, there was an increase in the abundance of Ruminoccocus bromii, a bacterium that promotes the growth of other beneficial bacteria capable of producing short-chain fatty acids.
These findings align with those of another recent small trial. That study indicated that FMT could substantially enhance the effectiveness of checkpoint inhibitors in individuals with non-small cell lung cancer, particularly when compared to patients receiving immunotherapy alone.
While these trials suggest that FMT might also be effective against other tumor types that respond to checkpoint inhibitors, such as those affecting the bladder and head and neck regions, comprehensive, large-scale randomized controlled trials are essential for confirmation. This perspective was shared by Elkrief.
Further research is also necessary to precisely identify which bacterial strains within faeces are beneficial. Such an understanding could pave the way for the development of artificial microbial formulations suitable for large-scale cancer treatment applications, as noted by Ianiro.