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World J Gastrointest Oncol. Jul 15, 2022; 14(7): 1218-1226
Published online Jul 15, 2022. doi: 10.4251/wjgo.v14.i7.1218
Gut microbiome and pancreatic cancer cachexia: An evolving relationship
Andrew Hendifar, Rasaq Akinsola, Hayato Muranaka, Arsen Osipov, Shant Thomassian, Natalie Moshayedi, Julianne Yang, Jonathan Jacobs, Suzanne Devkota, Neil Bhowmick, Jun Gong
Andrew Hendifar, Rasaq Akinsola, Hayato Muranaka, Arsen Osipov, Shant Thomassian, Natalie Moshayedi, Neil Bhowmick, Jun Gong, Department of Medicine, Division of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Julianne Yang, The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, University of California, Los Angeles, CA 90095, United States
Jonathan Jacobs, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA 90095, United States
Suzanne Devkota, Cedars-Sinai Medical Center, Department of Medicine, Inflammatory Bowel and Immunobiology Research Institute, University of California, Los Angeles, CA 90048, United States
Author contributions: Hendifar A and Gong J conceptualized the manuscript; Akinsola R, Muranaka H, Thomassian S, Moshayedi N, Yang J and Jacobs J analyzed the data; all authors have read and approve the final manuscript.
Supported by UCLA Clinical and Translational Science Institute UL1TR001881 Award.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jun Gong, MD, Assistant Professor, Department of Medicine, Division of Hematology and Oncology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, AC 1042B, Los Angeles, CA 90048, United States. jun.gong@cshs.org
Received: March 3, 2022
Peer-review started: March 3, 2022
First decision: April 17, 2022
Revised: May 10, 2022
Accepted: June 20, 2022
Article in press: June 20, 2022
Published online: July 15, 2022
Abstract

Nearly 80% of patients with pancreatic ductal adenocarcinoma (PDAC) develop cachexia along their disease course. Cachexia is characterized by progressive weight loss, muscle wasting, and systemic inflammation and has been linked to poorer outcomes and impairments in quality of life. Management of PDAC cachexia has historically involved a multidisciplinary effort comprised of nutritional support, pancreatic enzyme replacement therapy, and/or pharmacologic interventions. Despite current interventions to mitigate PDAC cachexia, a significant proportion of patients continue to die from complications associated with cachexia underscoring the need for novel insights and treatments for this syndrome. We highlight the feasibility and effectiveness of a recent enteral feeding prospective trial at our institution to improve cachexia outcomes in patients with advanced PDAC. Additionally, we were among the first to characterize the stool microbiome composition in patients with advanced PDAC receiving enteral feeding for the treatment of cachexia. Novel insights into the relationship between enteral nutritional support, cachexia, and the gut microbiome are presented. These promising results are discussed in the context of a potential ability to modulate the stool microbiome as a new interventional strategy to mitigate PDAC cachexia.

Keywords: Gut microbiome, Pancreatic cancer, Stool, Cachexia, Inflammation, Weight

Core Tip: Cachexia is a hallmark of pancreatic cancer and is characterized by muscle wasting, weight loss, and systemic inflammation. Despite advancements in nutritional support, pancreatic enzyme replacement therapy, and pharmacologic interventions for treating pancreatic cancer cachexia, it continues to have a significant negative impact on patient outcomes. We detail the results of a recent prospective clinical trial wherein cachectic patients with advanced pancreatic cancer achieved weight stability with 12 wk of enteral feeding. Notably, gut microbiome changes and an increased abundance of a specific microbe associated with enteral feeding highlight a potentially novel approach to mitigate cachexia through microbial modulation.