BACKGROUND AND AIM Fluoropyrimidines (FPs) are key drugs in many chemotherapy regimens; however, recipients are often prone to diarrhea due to gastrointestinal toxicity. Disruption of the intestinal epithelial barrier function by FPs leads to dysbiosis, which may exacerbate intestinal epithelial cell damage as a secondary effect and trigger diarrhea. However, despite studies on chemotherapy-induced changes in the intestinal microbiome of humans, the relationship between dysbiosis and diarrhea is unclear. In this study, we aimed to investigate the relationship between chemotherapy-induced diarrhea and the intestinal microbiome. METHODS We conducted a single-center prospective observational study. Twenty-three patients who received chemotherapy, including FPs as first-line chemotherapy for colorectal cancer, were included. Stool samples were collected before the start of chemotherapy and after one cycle of treatment to analyze intestinal microbiome composition and perform PICRUSt predictive metagenomic analysis. RESULTS Gastrointestinal toxicity was observed in 7 of 23 patients (30.4%), diarrhea was observed in 4 (17.4%), and nausea and anorexia were observed in 3 (13.0%). In 19 patients treated with oral FPs, the α diversity of the microbial community decreased significantly following chemotherapy only in the diarrheal group. At the phylum level, the diarrheal group showed a significant decrease in the abundance of Firmicutes and a significant increase in the abundance of Bacteroidetes with chemotherapy (p = 0.013 and 0.011, respectively). In the same groups, at the genus level, Bifidobacterium abundance was significantly decreased (p = 0.019). In contrast, in the non-diarrheal group, Actinobacteria abundance increased significantly with chemotherapy at the phylum level (p = 0.011). Further, Bifidobacterium, Fusicatenibacter, and Dorea abundance significantly increased at the genus level (p = 0.006, 0.019, and 0.011, respectively). The PICRUSt predictive metagenomic analysis revealed that chemotherapy caused significant differences in membrane transport in KEGG pathway level 2 and in 8 KEGG pathway level 3, including transporters and oxidative phosphorylation in the diarrhea group. CONCLUSION Organic-acid-producing bacteria seem to be involved in diarrhea associated with chemotherapy, including FPs.

中文翻译：

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化疗引起的腹泻与肠道微生物组组成之间的关系。

背景和目的 氟嘧啶（FP）是许多化疗方案中的关键药物；然而，由于胃肠道毒性，接受者常常容易出现腹泻。FP 破坏肠上皮屏障功能导致生态失调，继发效应可能会加剧肠上皮细胞损伤并引发腹泻。然而，尽管对化疗引起的人类肠道微生物组变化进行了研究，但生态失调与腹泻之间的关系尚不清楚。在本研究中，我们旨在探讨化疗引起的腹泻与肠道微生物群之间的关系。方法 我们进行了一项单中心前瞻性观察研究。纳入了 23 名接受化疗（包括 FP 作为结直肠癌一线化疗）的患者。在化疗开始前和一个治疗周期后收集粪便样本，以分析肠道微生物组组成并进行 PICRUSt 预测宏基因组分析。结果 23例患者中出现胃肠道毒性7例（30.4%），腹泻4例（17.4%），恶心、厌食3例（13.0%）。在 19 名接受口服 FP 治疗的患者中，仅腹泻组在化疗后微生物群落的 α 多样性显着下降。在门水平上，化疗后腹泻组的厚壁菌门丰度显着降低，拟杆菌门丰度显着增加（分别为 p = 0.013 和 0.011）。在同一组中，在属水平上，双歧杆菌丰度显着下降（p = 0.019）。相比之下，在非腹泻组中，放线菌丰度随着门水平的化疗而显着增加（p = 0.011）。此外，双歧杆菌、Fusicatenibacter 和 Dorea 丰度在属水平上显着增加（分别为 p = 0.006、0.019 和 0.011）。PICRUSt 预测宏基因组分析显示，化疗导致 KEGG 通路 2 级和 8 KEGG 通路 3 级的膜转运存在显着差异，包括腹泻组的转运蛋白和氧化磷酸化。结论 产生有机酸的细菌（包括 FP）似乎与化疗相关的腹泻有关。