Green tea extract prevents CPT-11-induced diarrhea by regulating the gut microbiota

Sci Rep. 2023 Apr 21;13(1):6537. doi: 10.1038/s41598-023-33731-w.

Abstract

Irinotecan (CPT-11) is an anticancer drug with indications for use in treating various cancers, but severe diarrhea develops as a side effect. We investigated the effects of green tea extract (GTE) on CPT-11-induced diarrhea, focusing on β-glucuronidase and intestinal UGT1A1. When CPT-11 was administered to rats alone, the fecal water content was approximately 3.5-fold higher in this group than in the control group, and diarrhea developed. The fecal water content in the GTE-treated group was significantly higher than that in the control group, but the difference was smaller than that between the group treated with CPT-11 alone and the control group, and diarrhea improved. When CPT-11 was administered alone, the abundances of Bacteroides fragilis and Escherichia coli, which are β-glucuronidase-producing bacteria, increased and interleukin-6 and interleukin-1β mRNA levels in the colon increased, but GTE suppressed these increases. CPT-11 decreased colon UGT1A1 and short-chain fatty acid levels; however, this decrease was suppressed in the GTE-treated group. The findings that GTE decreases the abundance of β-glucuronidase-producing bacteria and increases colon UGT1A1 levels, thereby decreasing the production of the active metabolite SN-38 in the intestinal tract, indicate that GTE ameliorates CPT-11-induced diarrhea.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic* / therapeutic use
  • Antioxidants / therapeutic use
  • Bacteria / metabolism
  • Camptothecin
  • Diarrhea / chemically induced
  • Diarrhea / drug therapy
  • Diarrhea / prevention & control
  • Gastrointestinal Microbiome*
  • Glucuronidase / genetics
  • Glucuronidase / metabolism
  • Irinotecan / adverse effects
  • Rats
  • Tea / adverse effects

Substances

  • Irinotecan
  • Camptothecin
  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Glucuronidase
  • Tea