Gut microbiome may influence pancreatic cancer survival
Click Here to Manage Email Alerts
Key takeaways:
- Long-term survivors of pancreatic cancer had significant enrichment of Faecalibacterium prausnitzii and Akkermansia muciniphilia.
- The relationship between these species and long-term survival remains unclear.
Stool from long-term survivors of pancreatic adenocarcinoma had an increased relative abundance of the bacterial species Faecalibacterium prausnitzii and Akkermansia muciniphilia, according to data published in Cancer.
Both species have previously been associated with immune response to cancer therapies, researchers noted.
“We were surprised to find that the species enriched in long-term survivors were those that have been previously associated with enhanced immune response to cancer treatment in preclinical studies, including Faecalibacterium prausnitzii,” Jordan Kharofa, MD, associate professor in the department of radiation oncology at University of Cincinnati College of Medicine, told Healio. “This piece of data along with several others in the preclinical space justifies further study of the relationship between the gut microbiome and pancreatic cancer treatment response.”
Methodology, results
The 5-year OS rate for patients with pancreatic adenocarcinoma stands below 10%, according to study background.
Delayed tumor growth as a result of unknown mechanisms that involve the fecal microbiota has been demonstrated in preclinical studies using fecal transplant experiments from long-term survivors of pancreatic adenocarcinoma. The fecal microbiome of patients with long-term survival, however, has not been well described.
Researchers conducted a cross-sectional study of stool from patients with pancreatic adenocarcinoma with long-term survival (n = 16), defined as having had a pancreatectomy and therapy more than 4 years prior without recurrence. They compared patients considered long-term survivors with control patients with pancreatic adenocarcinoma who had completed pancreatectomy and chemotherapy (n = 8).
All patients underwent pancreatectomy and chemotherapy prior to sample donation.
Researchers reported a median time from pancreatectomy of 6 years (range, 4-14) for long-term survivors with no evidence of disease and median DFS from pancreatectomy of 1.8 years in the control group, with no differences observed in overall microbial diversity between the two groups.
Results showed long-term survivors had significant enrichment of species relative abundance for the Ruminococacceae family, specifically Faecalibacterium prausnitzii and Akkermansia muciniphilia.
Next steps
The potential relationship between these bacterial species and long-term survival of patients with pancreatic adenocarcinoma remains unclear and will be studied further, according to Kharofa.
“The research in this space is still quite early,” he told Healio. “The interplay between the gut microbiome and the normal function of the immune system is becoming more apparent. Whether this can be exploited to assist in cancer therapy is of great interest but remains an open question.
“Potential mechanisms to do this would be through diet, oral bacterial supplementation or even fecal transplantation in some cases. Additional understanding of mechanisms as well as clinical trials will be needed to determine if any of these types of interventions will be effective,” he added.
For more information:
Jordan Kharofa, MD, can be reached at University of Cincinnati Cancer Center, 234 Goodman St. ML 0757, Cincinnati, OH 45267; email: kharofjr@ucmail.uc.edu.
Perspective
Back to Top
Suneel Kamath, MD
The data showing an association between relative abundance of Faecalibacterium prausnitzii and Akkermansia muciniphila and long-term survival in pancreatic cancer adds to the emerging literature connecting the gut microbiome with oncogenesis and cancer outcomes. This is of particular interest in pancreatic cancer, a highly lethal disease that is resistant to existing treatments, including traditional immunotherapies.
The study included 24 patients — 16 long-term survivors and eight controls — all of whom underwent pancreatectomy and adjuvant chemotherapy. This study is especially important because all included patients initially were diagnosed with nonmetastatic disease, whereas much of the literature on microbiome in pancreatic cancer has been in the metastatic setting.
Although there were no differences in overall stool microbial diversity between long-term survivors and controls, there was significant enrichment in Ruminococacceae family species, specifically Faecalibacterium prausnitzii and Akkermansia muciniphila.
Enrichment in Ruminococacceae family species is associated with improved response to immunotherapy in a number of studies in lung and renal cell cancers as well as melanoma. Pancreatic cancer remains highly resistant to traditional immune checkpoint inhibition, but it appears enrichment in Faecalibacterium prausnitzii and Akkermansia muciniphila mediates improved natural anti-tumor immune response. Enrichment in Akkermansia species also has been described in early-onset colorectal cancer and is associated with improved OS in that population, as well, perhaps for the same reasons.
We still don’t know if the observed differences in microbiome causally mediate improved survival or if they are simply bystanders to some other undetected prognostic factor. Early efforts to modulate the microbiome in melanoma and renal cell carcinoma have generated modest improvements in response to immunotherapy, but these are much more immune-sensitive diseases. There is much more to elucidate about the microbiome in pancreatic cancer, but it has been an exciting beginning so far.
Collapse
Read more about
Click Here to Manage Email Alerts