Recent results from a small clinical trial indicate that fecal microbiota transplants (FMTs) might enhance the effectiveness of immunotherapy in various gastrointestinal cancers. In this study, published on July 25 in the journal Cell Host & Microbe, six out of 13 patients who had previously resisted immune checkpoint inhibitors saw improvements after receiving FMTs from donors who had responded well to the treatment. The researchers also identified specific bacterial strains linked to either better or poorer responses to both FMT and immune checkpoint therapies.
Recent results from a small clinical trial indicate that fecal microbiota transplants (FMTs) might enhance the effectiveness of immunotherapy in various gastrointestinal cancers. In this study, published on July 25 in the journal Cell Host & Microbe, six out of 13 patients who had previously resisted immune checkpoint inhibitors saw improvements after receiving FMTs from donors who had responded well to the treatment. The researchers also identified specific bacterial strains linked to either better or poorer responses to both FMT and immune checkpoint therapies.
“This study emphasizes the intricate relationship between helpful and harmful bacteria in the gut microbiota and how it influences treatment outcomes,” stated co-corresponding author Hansoo Park from the Gwangju Institute of Science and Technology in South Korea. “As interest in the connection between gut microbiota and immune response to cancer treatments grows, our findings provide tangible evidence and new pathways for enhancing treatment results across a wider array of cancers.”
Though immune checkpoint inhibitors have transformed cancer therapy, many patients either do not respond or develop resistance post-initial treatment. The researchers chose to investigate FMT in patients on immune checkpoint inhibitors because emerging evidence suggests the gut microbiota plays a pivotal role in regulating the immune system, significantly affecting the effectiveness of these therapies. Some prior small clinical trials indicated that FMTs could help overcome resistance to immune checkpoint inhibitors in certain melanoma patients, but the potential for FMTs in other advanced solid tumors had not been examined until now. This study marks the first time this treatment’s potential benefits have been demonstrated in clinical settings outside melanoma.
The trial involved patients with metastatic solid tumors resistant to the anti-PD-1 drug nivolumab. Of these patients, four were diagnosed with gastric cancer, five with esophageal cancer, and four with hepatocellular carcinoma. The study involved six FMT donors who also had either gastric cancer, esophageal cancer, or hepatocellular carcinoma, and who had displayed a complete or partial response for at least six months following nivolumab or pembrolizumab treatment. FMTs were administered through colonoscopy after the recipients received antibiotics to reduce their own microbiotas.
“One of the most unexpected findings was from a hepatocellular carcinoma patient who initially showed no improvement after the first FMT and continued to experience cancer growth. However, after changing the donor for the second FMT, the patient showed an impressive reduction in tumor size,” noted co-corresponding author Sook Ryun Park from Asan Medical Center at the University of Ulsan College of Medicine in Seoul, South Korea. “Both donors had good long-term responses to anti-PD-1 inhibitors, but as we had yet to identify the bacteria responsible for the FMT response, we could not foresee whether the treatment would succeed.”
The researchers further examined which bacterial strains might influence the effectiveness of FMT along with checkpoint inhibitors. They discovered a new bacterial strain, Prevotella merdae Immunoactis, which improved the efficacy of FMTs, as well as two strains, Lactobacillus salivarius and Bacteroides plebeius, that negatively impacted FMT effectiveness.
They intend to continue their investigation of these and other strains, aiming to find improved methods for enhancing immunotherapy via gut microbiota modification. “By exploring the intricate interactions within the microbiome, we aspire to identify optimal microbial communities that can be harnessed to improve cancer treatment outcomes,” stated Hansoo Park. “This thorough approach aims to clarify how the complete microbial ecosystem contributes to therapeutic success.”
The researchers recognize the complexities involved in making FMT part of standard treatment widely, citing the absence of standardized protocols and regulatory guidelines, the risk of spreading pathogens, and logistical hurdles regarding mass production and distribution of FMT products. “Creating efficient and cost-effective production and distribution methods is crucial for broader adoption,” remarked Sook Ryun Park. “Addressing these challenges through comprehensive research and meticulous planning will be vital for incorporating FMT into standard cancer treatment practices.”
