A recent study conducted in South Korea indicates that fecal microbiota transplants (FMTs) could potentially improve the effectiveness of immunotherapies in patients with gastrointestinal (GI) cancers who have developed resistance to these treatments. The proof-of-concept clinical trial, led by researchers at the Gwangju Institute of Science and Technology (GIST), offers new insights into the interplay between gut microbiota and cancer therapy outcomes.
The study, published in Cell Host and Microbe, involved 13 patients with metastatic solid tumors that were resistant to the anti-PD-1 antibody drug nivolumab (Opdivo). These patients had either gastric cancer (4), esophageal cancer (5), or hepatocellular carcinoma (4). The FMT procedure involved colonoscopic implantation of fecal microbiota from donors who had previously shown complete or partial responses to anti-PD-1 drugs like nivolumab or pembrolizumab (Keytruda) for at least six months.
Impact of FMT on Immunotherapy-Resistant Cancers
Researchers found that 6 out of the 13 patients (46.2%) experienced benefits from the FMTs. Notably, one patient with hepatocellular carcinoma, who initially showed no response to the first FMT, exhibited remarkable tumor shrinkage after receiving a second transplant from a different donor. According to Sook Ryun Park, MD, PhD, from Asan Medical Center, "One of the most surprising results was from a [patient with] hepatocellular carcinoma who initially showed no response to the first [FMT] and continued to experience cancer progression. However, after switching the donor for the second [transplant], the patient exhibited remarkable tumor shrinkage."
Key Bacterial Strains Identified
The study also identified specific bacterial strains that influenced the effectiveness of FMTs. The presence of Prevotella merdae was associated with improved outcomes, while Lactobacillus salivarius and Bacteroides plebeius had detrimental effects. These findings highlight the complex role of the gut microbiome in modulating the response to cancer immunotherapy.
Challenges and Future Directions
Despite the promising results, the researchers acknowledge challenges to the widespread adoption of FMTs. Hansoo Park, MD, PhD, from GIST, noted, "This research highlights the complex interplay between beneficial and detrimental bacteria within the gut microbiota in determining treatment outcomes...our study provides concrete evidence and new avenues for improving treatment outcomes in a broader range of cancers." Addressing challenges such as efficient and cost-effective production and distribution methods is essential for integrating FMT into the standard of care for cancer treatment.
Further research and clinical trials are necessary to validate these findings and optimize FMT protocols for cancer treatment. The study underscores the potential for microbiome analysis to guide clinicians in treating patients with gastrointestinal cancers and improve therapeutic success by identifying optimal microbial communities.
