Microbiome Influence in Pancreatic Cancer

The human microbiome exerts a multifaceted influence on the initiation, progression and treatment response of pancreatic ductal adenocarcinoma (PDAC). Microbial communities in the gut, oral cavity and within tumour tissue interact with host immunity, metabolism and the tumour microenvironment. Dysbiosis, characterised by shifts in microbial diversity and the enrichment of specific taxa, can perpetuate chronic inflammation, alter barrier function and modulate antitumour immune surveillance. Microbiota‐derived metabolites, including tryptophan catabolites, shape systemic oxidative stress and autophagy in cancer cells, thereby affecting sensitivity to chemotherapeutic agents. Concurrently, non‐invasive profiling of faecal and salivary microbiota has yielded promising diagnostic and prognostic biomarkers, offering potential for early detection and personalised risk stratification. Advances in shotgun metagenomics, metabolomics and integrated multi‐omics approaches are refining our understanding of microbe–host interactions in PDAC and paving the way for microbiome‐based therapeutics and dietary interventions.

Research from Nature Portfolio

Recent studies have shown that the tryptophan‐derived microbial metabolite indole-3-acetic acid (3-IAA) is enriched in patients who respond to first-line chemotherapy for PDAC and that modulation of faecal microbiota or direct 3-IAA administration enhances chemotherapeutic efficacy in humanised mouse models. Neutrophil‐derived myeloperoxidase mediates 3-IAA oxidation, resulting in reactive oxygen species accumulation and suppression of autophagy in tumour cells. In parallel, analysis of faecal microbial communities in patients with pancreatic adenocarcinoma has identified a set of bacterial features capable of discriminating cancer from controls with high accuracy. A machine-learning classifier based on these faecal signatures achieved area under the receiver operating characteristic curve values exceeding 0.80, although inter-individual variability and stage specificity highlight the need for larger prospective validation.

Microbiome Influence in Pancreatic Cancer publication trend

The graph below shows the total number of articles in microbiome influence in pancreatic cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Dysbiosis: A disturbance in the composition or function of the microbiome that can promote disease processes.

Indole-3-acetic acid (3-IAA): A microbial catabolite of tryptophan that can modulate reactive oxygen species and autophagy in cancer cells.

Shotgun metagenomics: A sequencing approach that captures the collective genomes of microbial communities to identify species and functional genes.

Biomarker: A measurable indicator, such as a microbial species or metabolite, used for diagnosis, prognosis or monitoring of disease.

Pancreatic ductal adenocarcinoma (PDAC): The most common and aggressive form of pancreatic cancer arising from the ductal epithelium.

References

1. Microbiota-derived 3-IAA influences chemotherapy efficacy in pancreatic cancer. Nature (2023).
2. A faecal microbiota signature with high specificity for pancreatic cancer. Gut (2022).
3. Metagenomic Identification of Microbial Signatures Predicting Pancreatic Cancer From a Multinational Study. Gastroenterology (2022).
4. The microbiota and microbiome in pancreatic cancer: more influential than expected. Molecular Cancer (2019).