Wang Kaicen, Wu Wenrui, Wang Qing, Yang Liya, Bian Xiaoyuan, Jiang Xianwan, Lv Longxian, Yan Ren, Xia Jiafeng, Han Shengyi, Li Lanjuan
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Jinan Microecological Biomedicine Shandong Laboratory, Jinan, China.
Front Microbiol. 2022 Oct 14;13:932047. doi: 10.3389/fmicb.2022.932047. eCollection 2022.
The bidirectional relationship between colorectal cancer (CRC) and the gut microbiome has been well-documented. Here, we investigated the impact of -mediated post-antibiotic gut microbial reconstitution on the development of colitis-associated CRC (CAC). The results showed that post-antibiotic replenishment of worsened the tumorigenesis of CAC as indicated by increased number of large (>2 mm in diameter) tumors and both average and total tumor diameters. Measures of intestinal barrier function showed that post-antibiotic gavage damaged the intestinal barrier as reflected by lower transcriptional levels of , and . Impaired gut barrier was followed by lipopolysaccharides (LPS) translocation as indicated by higher level of serum LPS-binding protein (LBP). The increased colonic mRNA levels of , and and serum levels of IL-1β, IL-6, and TNF-α indicated that post-antibiotic replenishment resulted in overactivated inflammatory environment in CAC. The analysis of the evolution of the microbial community during the progression of CAC showed that post-antibiotic supplementation of led to a distinct microbial configuration when compared with other treatments characterized by enriched Firmicutes, Lachnospiraceae, and Ruminococcaceae, and depleted Bacteroidetes, which was accompanied by higher Firmicutes/Bacteroidetes (F/B) ratio. Furthermore, post-antibiotic administration changed the bile acid (BA) metabolic profile as indicated by decreased concentrations of secondary BA (SBA), ω-murocholic acid (ωMCA), and murocholic acid (muroCA). In addition, the supplementation after antibiotic pretreatment also impacted the metabolism of short-chain fatty acids (SCFAs) as evidenced by increased concentrations of acetic acid, propionic acid, butyric acid, and valeric acid. Our study surprisingly observed that -mediated post-antibiotic reconstitution of the gut microbiota aggravated the CAC in mice. It might exert its effect by damaging the gut barrier, exacerbating inflammatory responses, disrupting the post-antibiotic recovery of the microbial community, and further influencing the metabolism of BA and SCFAs. These findings indicated that maintaining the homeostasis of intestinal microorganisms is more crucial to health than replenishing a single beneficial microbe, and probiotics should be used with caution after antibiotic treatment.
结直肠癌(CRC)与肠道微生物群之间的双向关系已有充分记录。在此,我们研究了介导的抗生素后肠道微生物重建对结肠炎相关结直肠癌(CAC)发生发展的影响。结果表明,抗生素后补充会恶化CAC的肿瘤发生,表现为直径大于2毫米的大肿瘤数量增加,以及平均肿瘤直径和总肿瘤直径均增加。肠道屏障功能的检测表明,抗生素后灌胃会损害肠道屏障,表现为、和的转录水平降低。肠道屏障受损后,脂多糖(LPS)发生易位,表现为血清LPS结合蛋白(LBP)水平升高。结肠中、和的mRNA水平升高以及血清中IL-1β、IL-6和TNF-α水平升高表明,抗生素后补充会导致CAC中炎症环境过度激活。对CAC进展过程中微生物群落演变的分析表明,与其他以厚壁菌门、毛螺菌科和瘤胃球菌科富集以及拟杆菌门减少为特征的治疗相比,抗生素后补充会导致独特的微生物结构,同时伴有更高的厚壁菌门/拟杆菌门(F/B)比率。此外,抗生素后给药改变了胆汁酸(BA)代谢谱,表现为次级BA(SBA)、ω-鼠胆酸(ωMCA)和鼠胆酸(muroCA)浓度降低。此外,抗生素预处理后补充也影响了短链脂肪酸(SCFA)的代谢,表现为乙酸、丙酸、丁酸和戊酸浓度增加。我们的研究令人惊讶地发现,介导的抗生素后肠道微生物群重建会加重小鼠的CAC。它可能通过破坏肠道屏障、加剧炎症反应、扰乱抗生素后微生物群落的恢复以及进一步影响BA和SCFA的代谢来发挥作用。这些发现表明,维持肠道微生物的稳态对健康比补充单一有益微生物更为关键,抗生素治疗后应谨慎使用益生菌。
Front Microbiol. 2017-9-26
Front Cell Infect Microbiol. 2021
Front Microbiol. 2019-10-1
AIMS Microbiol. 2022-12-22
Probiotics Antimicrob Proteins. 2025-7-9
Stem Cell Res Ther. 2021-8-18
Cancer Immunol Res. 2021-10
Appl Microbiol Biotechnol. 2021-8
Int J Mol Sci. 2021-6-10
Onco Targets Ther. 2020-12-21