Rifaximin alleviates irinotecan-induced diarrhea in mice model

• Published in: Annals of medicine (Helsinki) Vol. 56; no. 1; p. 2429029
• Main Authors: Huang, Chengyi, Lan, Huiyin, Bai, Minghua, Chen, Jinggang, Xu, Shengkun, Sun, Quanquan, Chen, Qianping, Mao, Wei, Jiang, Jin, Zhu, Ji
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.12.2024; Taylor & Francis Group
• Subjects: Animals; diarrhea; Diarrhea - chemically induced; Diarrhea - drug therapy; Diarrhea - prevention & control; Disease Models, Animal; Gastrointestinal Microbiome - drug effects; Glucuronidase - metabolism; gut microbiota; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestinal Mucosa - microbiology; Intestinal Mucosa - pathology; Irinotecan; Male; Mice; Mice, Inbred BALB C; Mucositis - chemically induced; Mucositis - drug therapy; Mucositis - prevention & control; Rifamycins - pharmacology; Rifamycins - therapeutic use; Rifaximin; Rifaximin - pharmacology; Rifaximin - therapeutic use; Toxicology; Rifaximin; irinotecan; diarrhea; gut microbiota
• ISSN: 0785-3890; 1365-2060; 1365-2060
• DOI: 10.1080/07853890.2024.2429029

Irinotecan is a chemotherapeutic drug widely used to treat solid tumors. However, its effectiveness is limited by the severely delayed onset of diarrhea. This study aimed to confirm the protective effects of the non-systemic oral antibiotic rifaximin on irinotecan-induced mucositis in mice model. Six to eight week-old BALB/c mice were treated with saline, irinotecan (50 mg/kg, i.p. once daily), rifaximin (50 mg/kg, p.o. twice daily), or irinotecan + rifaximin for 9 consecutive days. Signs of diarrhea, bloody diarrhea, and body weight were monitored daily. Intestinal tissues were harvested for histopathological analysis and quantitative PCR. SN38 and SN38G concentration in intestine were detected using LC-MS analysis. Intestinal bacteria β-glucuronidase (BGUS) activity was detected using mouse feces. We performed 16S rRNA sequencing to investigate the gut microbiota composition. Gut permeability was tested by measuring the fluorescein isothiocyanate-dextran intensity in the serum. Rifaximin reduced the frequency of delayed diarrhea and attenuated the severity of diarrhea caused by irinotecan in mice. Rifaximin significantly inhibited SN38 exposure in intestine and irinotecan-induced increase in BGUS activity. Rifaximin alleviated intestinal mucosal inflammation, prevented intestinal epithelial damage caused by irinotecan, and maintained gut barrier function. Moreover, the consecutive use of rifaximin did not cause a disorder in gut microbiota and reduced irinotecan-induced Firmicutes expansion. More importantly, rifaximin inhibited the expansion of some microbiota (such as , , and f_Enterobacteriaceae) and promoted an increase in beneficial microbiota (such as , , and f_Oscillospiraceae). Preventive use of rifaximin is a feasible method to protect against irinotecan-induced diarrhea.