Findings from a small, proof-of-concept clinical trial have suggested that fecal microbiota transplants (FMTs) may increase the effectiveness of immunotherapy in a range of gastrointestinal cancers. In the study, published July 25 in the journal Cell host and microbe6 of 13 patients who had previously shown resistance to immune checkpoint inhibitors benefited from receiving FMTs from donors who had previously responded to treatment. The researchers also identified specific bacterial strains associated with better or worse responses to FMT and immune checkpoint agents.
“This study highlights the complex interplay between beneficial and harmful bacteria in the gut microbiota in determining treatment outcomes,” said co-corresponding author Hansoo Park of the Gwangju Institute of Science and Technology in Gwangju, South Korea. “While the link between the gut microbiota and the immune response to cancer therapy is a growing area of interest, our study provides concrete evidence and new opportunities to improve treatment outcomes in a broader range of cancers.”
Immune checkpoint inhibitors have revolutionized cancer treatment, but many patients never respond or develop resistance after an initial response. The researchers decided to study FMT in patients receiving immune checkpoint inhibitors because emerging evidence suggests that the gut microbiota plays a critical role in modulating the immune system and may significantly impact the efficacy of these therapies. Previous small clinical trials had reported that FMTs could overcome resistance to immune checkpoint inhibitors in some melanoma patients, but the potential of FMTs to overcome resistance in other advanced solid cancers had not been explored. This study is the first to demonstrate the potential benefits of this treatment in a clinical setting outside of melanoma.
The study enrolled patients with metastatic cancer from solid tumors that were resistant to the anti-PD-1 drug nivolumab. Four had gastric cancer, five had esophageal cancer and four had hepatocellular carcinoma. The six FMT donors, who also had gastric cancer, esophageal cancer or hepatocellular carcinoma, had had a complete or partial response for at least 6 months after treatment with nivolumab or pembrolizumab. The FMTs were administered via colonoscopy after recipients received antibiotics to target their own microbiota.
“One of the most surprising results was that of a hepatocellular carcinoma patient who initially showed no response to the first FMT and continued to experience cancer progression. However, after switching donors for the second FMT, the patient showed remarkable tumor shrinkage,” says co . -corresponding author Sook Ryun Park, from the Asan Medical Center at the University of Ulsan College of Medicine in Seoul, South Korea. “Both donors responded long-term and well to anti-PD-1 inhibitors, but because we did not yet know the causative bacteria responsible for the FMT response, we could not predict whether the treatment would be effective.”
The researchers then took a closer look at which bacteria were most likely to influence whether patients benefited from FMT in combination with checkpoint inhibitors. In doing so, they identified a new bacterial strain that helped improve the effectiveness of FMT. Prevotella merdae Immunoactis. They also identified two strains that adversely affected the efficacy of FMT: Lactobacillus salivarius And Bacteroides plebeius.
They plan to continue studying these and other strains with the goal of developing better ways to increase the effectiveness of immunotherapy by altering the gut microbiota. “By examining the complex interactions within the microbiome, we hope to identify optimal microbial communities that can be used to improve cancer treatment outcomes,” says Hansoo Park. “This comprehensive approach will help us understand how the microbial ecosystem as a whole contributes to therapeutic success.”
The researchers acknowledge the challenges of adopting FMT as part of standard treatment on a broad scale, including the lack of standardized protocols and regulatory guidelines, the potential risks of pathogen transmission, and logistical issues surrounding the large-scale production and distribution of FMT products . “Developing efficient and cost-effective methods for production and distribution is necessary for widespread adoption,” says Sook Ryun Park. “Addressing these challenges through extensive research and careful planning will be essential to integrating FMT into the standard of care for cancer treatment.”
