Metabolites derived from gut microbiota mitigate chemoresistance in pancreatic cancer

Abstract

ABSTRACT Introduction Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of tumor-related deaths. The gut microbiota has gained attention in cancer treatment, due to its influence on the immune system and drug activity. Areas covered Tintelnot and collaborators highlight distinct gut microbiota composition in metastatic PDAC (mPDAC) patients responding versus non-responding to chemotherapy. In the context of chemotherapy treatment, the gut microbiota of responders can metabolize tryptophan from food into indole-3-acetic acid (3-IAA). The presence of neutrophil-derived myeloperoxidase facilitates the role of 3-IAA in promoting the accumulation of reactive oxygen species in tumor cells. This accumulation, in turn, inducing tumor cell cytotoxicity. Additionally, 3-IAA can inhibit tumor cell autophagy activity, diminishing tumor cells’ ability to adapt to cell stress. This manuscript provides a comprehensive analysis of the latest research on microbiota, metabolites, and PDAC, sourced from PubMed, ScienceDirect, and Google Scholar. Expert opinion The evaluated study noted an elevation of the bacterial metabolite 3-IAA in responsive PDAC patients’ serum, suggesting its potential to enhance chemotherapy sensitivity. Gaining a thorough comprehension of the impact of gut microbiota metabolites on drug activity is beneficial for broadening our strategies to mitigate chemotherapy resistance in tumors and identifying markers that predict chemotherapy outcomes.