Unraveling the gut microbiome's contribution to pancreatic ductal adenocarcinoma: mechanistic insights and therapeutic perspectives

Eileen Tabrizi; Fatemeh Pourteymour Fard Tabrizi; Gehad Mahmoud Khaled; Michael P Sestito; Saeid Jamie; Brian A Boone

doi:10.3389/fimmu.2024.1434771

Unraveling the gut microbiome's contribution to pancreatic ductal adenocarcinoma: mechanistic insights and therapeutic perspectives

Front Immunol. 2024 Jul 9:15:1434771. doi: 10.3389/fimmu.2024.1434771. eCollection 2024.

Authors

Eileen Tabrizi^{1

2}, Fatemeh Pourteymour Fard Tabrizi³, Gehad Mahmoud Khaled⁴, Michael P Sestito⁵, Saeid Jamie⁶, Brian A Boone^{1

5}

Affiliations

¹ Department of Microbiology, Immunology and Cell Biology, School of Medicine, West Virginia University, Morgantown, WV, United States.
² Cancer Institute, West Virginia University, Morgantown, WV, United States.
³ Department of Community Nutrition, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, East Azerbaijan, Iran.
⁴ Department of Biotechnology, School of Sciences and Engineering, American University in Cairo, New Cairo, Cairo, Egypt.
⁵ Department of Surgery, West Virginia University School of Medicine, Morgantown, WV, United States.
⁶ Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.

Abstract

The gut microbiome plays a significant role in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC), influencing oncogenesis, immune responses, and treatment outcomes. Studies have identified microbial species like Porphyromonas gingivalis and Fusobacterium nucleatum, that promote PDAC progression through various mechanisms. Additionally, the gut microbiome affects immune cell activation and response to immunotherapy, including immune checkpoint inhibitors and CAR-T therapy. Specific microbes and their metabolites play a significant role in the effectiveness of immune checkpoint inhibitors (ICIs). Alterations in the gut microbiome can either enhance or diminish responses to PD-1/PD-L1 and CTLA-4 blockade therapy. Additionally, bacterial metabolites like trimethylamine N-oxide (TMAO) and lipopolysaccharide (LPS) impact antitumor immunity, offering potential targets to augment immunotherapy responses. Modulating the microbiome through fecal microbiota transplantation, probiotics, prebiotics, dietary changes, and antibiotics shows promise in PDAC treatment, although outcomes are highly variable. Dietary modifications, particularly high-fiber diets and specific fat consumption, influence microbiome composition and impact cancer risk. Combining microbiome-based therapies with existing treatments holds potential for improving PDAC therapy outcomes, but further research is needed to optimize their effectiveness.

Keywords: antibiotic therapy; bacteriotherapy; dysbiosis; immune modulation; microbiome; pancreatic ductal adenocarcinoma (PDAC).

Publication types

Review

MeSH terms

Animals
Carcinoma, Pancreatic Ductal* / immunology
Carcinoma, Pancreatic Ductal* / microbiology
Carcinoma, Pancreatic Ductal* / therapy
Fecal Microbiota Transplantation
Gastrointestinal Microbiome* / immunology
Humans
Immune Checkpoint Inhibitors / therapeutic use
Immunotherapy / methods
Pancreatic Neoplasms* / immunology
Pancreatic Neoplasms* / microbiology
Pancreatic Neoplasms* / therapy
Probiotics / therapeutic use

Substances

Immune Checkpoint Inhibitors

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number CoBRE award (5P20GM121322). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.