SEARCHNARRATIVE_REVIEWoncology, gastroenterology

narrative_review·oncology, gastroenterology, immunology, systematic review·PMC10649877

Pancreatic Exocrine Insufficiency and the Gut Microbiome in Pancreatic Cancer: A Target for Future Diagnostic Tests and Therapies?

Cancers · 8 authors, 7 centres

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TL;DR

This narrative literature review synthesizes evidence that pancreatic exocrine insufficiency in pancreatic cancer patients is linked to gut microbiome dysbiosis, which may contribute to poorer treatment outcomes.

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This narrative literature review examines the relationship between pancreatic exocrine insufficiency (PEI), gut microbiome dysbiosis, and pancreatic cancer outcomes. Differences in intestinal microbiome composition between patients with short-term and long-term survival have been demonstrated using 16S rRNA gene sequencing. However, the authors acknowledge that the mechanisms linking PEI, dysbiosis, and outcomes are not fully understood and that findings regarding specific microbiome changes remain associative rather than causative.

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narrative_review

SPECIALTY

oncology

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ORIGINAL PAPER

PMC10649877

Pancreatic Exocrine Insufficiency and the Gut Microbiome in Pancreatic Cancer: A Target for Future Diagnostic Tests and Therapies?

Cancers

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ABSTRACT

Abstract Simple Summary It is now thought that bacteria in the gut and tumour of patients with pancreatic cancer play an important role in the growth of the cancer and its sensitivity to chemotherapy. It has been shown that pancreatic exocrine insufficiency (PEI), common in pancreatic cancer patients, is linked to poorer outcomes. Conversely, it has also been demonstrated that treatment with pancreatic enzyme replacement therapy (PERT) can improve survival in pancreatic cancer patients. The reasons for this are not fully understood, but it is possible that PEI alters the gut and tumour microbiome of pancreatic cancer patients towards a less favourable composition, whereas PERT can reverse these changes and make the gut and tumour microbiome more favourable. If true, this could represent an opportunity for the development of new diagnostic tests and therapies for pancreatic cancer, which remains one of the deadliest cancers. Abstract Pancreatic exocrine insufficiency (PEI) is common amongst pancreatic cancer patients and is associated with poorer treatment outcomes. Pancreatic enzyme replacement therapy (PERT) is known to improve outcomes in pancreatic cancer, but the mechanisms are not fully understood. The aim of this narrative literature review is to summarise the current evidence linking PEI with microbiome dysbiosis, assess how microbiome composition may be impacted by PERT treatment, and look towards possible future diagnostic and therapeutic targets in this area. Early evidence in the literature reveals that there are complex mechanisms by which pancreatic secretions modulate the gut microbiome, so when these are disturbed, as in PEI, gut microbiome dysbiosis occurs. PERT has been shown to return the gut microbiome towards normal, so called rebiosis, in animal studies. Gut microbiome dysbiosis has multiple downstream effects in pancreatic cancer such as modulation of the immune response and the response to chemotherapeutic agents. It therefore represents a possible future target for future therapies. In conclusion, it is likely that the gut microbiome of pancreatic cancer patients with PEI exhibits dysbiosis and that this may potentially be reversible with PERT. However, further human studies are required to determine if this is indeed the case. Keywords: pancreatic cancer, microbiome, pancreatic exocrine insufficiency, pancreatic enzyme replacement therapy

CITATION EXPORT

James M Halle-Smith, Lewis A Hall, Sarah F Powell-Brett et al.. Pancreatic Exocrine Insufficiency and the Gut Microbiome in Pancreatic Cancer: A Target for Future Diagnostic Tests and Therapies?. Cancers. (2023). https://doi.org/10.3390/cancers15215140

AUTHORS

8 · 7 CENTRES

James M Halle-Smith, Lewis A Hall, Sarah F Powell-Brett, Nabeel Merali, Adam E Frampton, Andrew D Beggs, Paul Moss, Keith J Roberts

1Hepatobiliary and Pancreatic Surgery Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, [email protected] (K.J.R.)
2Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2GW, UK; [email protected]
3Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK
4Section of Oncology, Department of Clinical & Experimental Medicine, University of Surrey, Guildford GU2 7WG, [email protected] (A.E.F.); [email protected] (P.M.)
5Minimal Access Therapy Training Unit (MATTU), Leggett Building, University of Surrey, Guildford GU2 7WG, UK
6Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
7Colorectal Surgery Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, UK