New research explores gut microbiota’s role in pancreatic cancer diagnosis and therapy, sparking hope for innovative screening and treatment options.
Study: Gut Dysbiosis and Fecal Microbiota Transplantation in Pancreatic Cancer: Current Status and Perspectives. Image Credit: TopMicrobialStock/Shutterstock.com
A recent review in Cancer Screening and Prevention examines how the gut microbiome influences immunity, metabolism, and the tumor environment in pancreatic ductal adenocarcinoma (PDAC), a cancer with one of the highest mortality rates.
The review highlights gut microbiome-based anti-cancer strategies, potential for early PDAC screening through microbial signatures, and fecal microbiota transplantation (FMT) as a future treatment. It also addresses challenges in gut microbiome research and suggests ways to overcome them.
Background
Pancreatic ductal adenocarcinoma (PDAC), the most common and severe type of pancreatic cancer, accounts for over 80% of cases and causes more than 446,000 deaths annually.
Despite advances in treatment, PDAC has a five-year survival rate of just 10%, with nearly 90% of patients succumbing within a year due to delayed detection. Only 15–20% of cases are eligible for surgical removal at diagnosis.
Growing interest in diet and gut microbiota’s role in chronic diseases has driven metagenomic research, which explores microbial signatures for early cancer detection and potential treatments.
Fecal microbiota transplantation and PDAC gut dysbiosis
Fecal microbiota transplantation (FMT) is an ancient yet poorly understood medical treatment procedure involving transferring fecal products (beneficial microbiota) from a healthy donor's stools into a patient's digestive tract.
First recorded in traditional Chinese medicine (~300 AD), FMT has historically been ignored in Western medicine due to concerns about its safety and efficacy.
The intervention has recently experienced a resurgence of interest from within the scientific community due to a growing body of evidence highlighting its chemotherapy-enhancing properties and ability to attenuate adverse chemotherapeutic reactions.
Unfortunately, the mechanisms underpinning FMT's benefits remain largely elusive. Comparisons between the gut microbial compositions of healthy individuals and PDAC patients (revealed through RNA sequencing and metagenomic characterization) have revealed stark contrasts, with PDAC patients demonstrating enrichments in Streptococcus and Veillonella populations alongside significant reductions in Faecalibacterium species. Research has further hinted at the gut dysbiosis impacts of Helicobacter pylori infections, which correlate with significant increases in PDAC risk.
Gut microbial assemblages are highly variable across human ethnic- and geographical populations, with evidence of even siblings differing in their baseline (healthy) gut floral compositions.
This extensive variation hinders the establishment of standardized microbial signature-leveraging diagnostic procedures and complicates research on FMT outcomes.
Encouragingly, the advent of machine learning algorithms and the development of high-throughput 'next-generation' sequencing technologies have revealed a handful of fecal metagenomic classifiers capable of identifying PDAC substantially earlier than conventional screening approaches.
Metabolomics and FMT's potential in PDAC treatment
Metabolites, produced during growth, play key roles in diseases like cancer. Metabolomics shows that butyric acid from butyrate-producing bacteria can aid PDAC cell differentiation and reduce invasiveness.
PDAC patients have fewer butyrate-producing bacteria and lower levels of butyric acid and chemotherapy-boosting indole-3-acetic acid. Adjusting gut metabolite levels through microbial composition may improve PDAC outcomes, as gut health influences systemic therapy efficacy. Notably, PDAC patients on antibiotics often have poorer survival rates.
Future research aims to explore gut microbiota's role in supporting PDAC treatments, with fecal microbiota transplantation (FMT) as a promising approach. While animal studies show FMT’s potential to slow tumor growth and improve survival, human trials face risks like multidrug-resistant infections, emphasizing the need for rigorous donor screening and monitoring.
Conclusions
Gut microbial characterization and microbiome-leveraging interventions (e.g., FMT) show great promise in expediting PDAC detection (early screening) and attenuating disease pathophysiology. While a relatively novel field of clinical investigation, ongoing advances in next-generation metagenomic sequencing and metabolomic models may revolutionize future PDAC treatment.
However, care must be taken to ensure sufficient and routine donor screening and post-PDAC follow-up to prevent transplantation complications that have plagued previous human clinical trials.
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