基于5-氟尿嘧啶（5-FU）的辅助化疗，如FOLFOX，被建议作为胃肠癌的一种治疗方法。然而，肠道损伤仍然是一种普遍存在的副作用，没有实用的预防措施。我们调查了八宝丹（BBD），一种中药，通过控制免疫应答和肠道微生物群保护5-FU引起的肠道损伤。首先，采用腹腔注射方式给小鼠注射5-FU建立小鼠模型，然后连续五天灌胃250 mg/kg的BBD。5-FU导致显著的体重下降，腹泻，粪便出血和组织病理学上的肠道损伤。BBD的给予减轻了这些症状，抑制了促炎细胞因子（IL-6、IL-1β、IFN-γ、TNF-α）的分泌，并增加了CD3（+）T细胞的比例和CD4（+）/CD8（+）比值。根据16S rRNA测序，BBD在时间依赖性的方式下显著修复了肠道微生物群的紊乱，并增加了厚壁菌门/拟杆菌门（F/B）比值。转录组学结果显示，其机制主要集中在NF-κB途径上，并发现BBD减少了粪便悬液和血清中的LPS浓度，并抑制了TLR4/MyD88/NF-κB途径的激活。此外，根据属水平上的结果，BBD在第五天上调了未鉴定_Corynebacteriaceae、Aerococcus、Blautia、Jeotgalicoccus、Odoribacter、Roseburia、Rikenella、Intestinimonas、未鉴定_Lachnospiraceae、Enterorhabdus、Ruminiclostridium的丰度，下调了Bacteroides、Parabacteroides、Parasutterella、Erysipelatoclostridium的丰度，这些与肠道损伤或TLR4/MyD88/NF-κB途径密切相关。总之，我们建立了一个涉及5-FU、BBD、免疫应答、肠道微生物群和关键途径的网络，以解释口服BBD在预防5-FU诱导的肠道损伤中的药理学。版权所有 © 2023. 由Elsevier Masson SAS出版。

Adjuvant chemotherapy based on 5-fluorouracil (5-FU), such as FOLFOX, is suggested as a treatment for gastrointestinal cancer. Yet, intestinal damage continues to be a prevalent side effect for which there are no practical prevention measures. We investigated whether Babao Dan (BBD), a Traditional Chinese Medicine, protects against intestinal damage induced by 5-FU by controlling immune response and gut microbiota. 5-FU was injected intraperitoneally to establish the mice model, then 250 mg/kg BBD was gavaged for five days straight. 5-FU led to marked weight loss, diarrhea, fecal blood, and histopathologic intestinal damage. Administration of BBD reduced these symptoms, inhibited proinflammatory cytokine (IL-6, IL-1β, IFN-γ, TNF-α) secretion, and upregulated the ratio of CD3(+) T cells and the CD4(+)/CD8(+) ratio. According to 16S rRNA sequencing, BBD dramatically repaired the disruption of the gut microbiota caused in a time-dependent way, and increased the Firmicutes/Bacteroidetes (F/B) ratio. Transcriptomic results showed that the mechanism is mainly concentrated on the NF-κB pathway, and we found that BBD reduced the concentration of LPS in the fecal suspension and serum, and inhibited TLR4/MyD88/NF-κB pathway activation. Furthermore, at the genus level on the fifth day, BBD upregulated the abundance of unidentified_Corynebacteriaceae, Aerococcus, Blautia, Jeotgalicoccus, Odoribacter, Roseburia, Rikenella, Intestinimonas, unidentified_Lachnospiraceae, Enterorhabdus, Ruminiclostridium, and downregulated the abundance of Bacteroides, Parabacteroides, Parasutterella, Erysipelatoclostridium, which were highly correlated with intestinal injury or the TLR4/MyD88/NF-κB pathway. In conclusion, we established a network involving 5-FU, BBD, the immune response, gut microbiota, and key pathways to explain the pharmacology of oral BBD in preventing 5-FU-induced intestinal injury.Copyright © 2023. Published by Elsevier Masson SAS.