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

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.

SUBMITTER: Kon R

PROVIDER: S-EPMC10121581 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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

Kon Risako R Ikarashi Nobutomo N Yamaguchi Arisa A Teshima Yuka Y Yamaguchi Tamami T Miyaoka Kanako K Fukuda Moeno M Noguchi Hinata H Tomimoto Rei R Sakai Hiroyasu H Kamei Junzo J Hosoe Tomoo T

Scientific reports 20230421 1

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 sig ...[more]

PMID: 37085597

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Project description:BackgroundMetabolic syndrome (MetS) is a common metatoblic disorder that leads to various adverse health outcomes such as diabetes and cardiovascular diseases (CVDs). Recent studies suggested that MetS-associated gut dysbiosis could exacerbate MetS related diseases. Green tea, a popular beverage rich in polyphenols, has showed antioxidant and anti-inflammatory effects in treating MetS through gut modulation.ObjectivesThis study aimed to understand the impact of green tea extract (GTE) on the composition and metabolism of gut microbiota from people with MetS.MethodsWe utilized an in-vitro human colonic model (HCM) to specifically investigate the host-free interactions between GTE and gut microbiota of MetS adults. Fresh fecal samples donated by three adults with MetS were used as gut microbe inoculum in our HCM system. 16S ribosomal RNA sequencing and liquid-chromatography mass spectrometry (LC/MS) combined with QIIME 2, Compound Discoverer 3.1 and MetaboAnalyst 4.0 based data analyses were performed to show the regulating effects of GTE treatment on gut microbial composition and their metabolism.ResultsOur data suggested that GTE treatment in HCM system modified composition of MetS gut microbiota at genus level and led to significant microbiota metabolic profile change. Bioinformatics analysis showed relative abundance of Escherichia and Klebsiella was commonly increased while Bacteroides, Citrobacter, and Clostridium were significantly reduced. All free fatty acids detected were significantly increased in different colon sections. Lipopolysaccharide biosynthesis, methane metabolism, pentose phosphate pathway, purine metabolism, and tyrosine metabolism were regulated by GTE in MetS gut microbiota. In addition, we identified significant associations between altered microbes and microbial metabolites.ConclusionsOverall, our study revealed the impact of GTE treatment on gut microbiota composition and metabolism changes in MetS microbiota in vitro, which may provide information for further mechanistic investigation of GTE in modulating gut dysbiosis in MetS.

Dataset Information

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

Publications

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

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