Zheng Haihui, Chen Mingyi, Li Yuan, Wang Yuanyuan, Wei Lin, Liao Ziqiong, Wang Mengxia, Ma Fangli, Liao Qiongfeng, Xie Zhiyong
School of Pharmaceutical Sciences, Sun Yat-sen UniversityGuangzhou, China.
School of Chinese Materia Medica, Guangzhou University of Chinese MedicineGuangzhou, China.
Front Microbiol. 2017 Sep 7;8:1703. doi: 10.3389/fmicb.2017.01703. eCollection 2017.
Inflammatory bowel disease (IBD) results from alterations in intestinal flora and the immune system. Sulfasalazine (SASP) is a sulfa antimicrobial used to treat IBD in clinic for years. However, how SASP affects gut microbes and its potential functions remains unclear. To investigate the relationships of SASP, IBD, and gut microbiome, we used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis in rats, and analyzed the microbiota in the fecal samples, which come from the control group (treated with ethanol + saline), the model group (treated with TNBS-ethanol + saline) and the SASP group (treated with TNBS-ethanol + SASP), with 16S gene sequencing and followed up a subset sample using shotgun sequencing. The study found that SASP treatment could not only restore the TNBS-induced gut dysbiosis, which was proved by the increasing amount of SCFAs-producing bacteria and lactic acid-producing bacteria as well as the decreasing amount of Proteobacteria, but also modulate the dysregulated function of the TNBS-induced colitis to resemble that of the control group, including an increased capacity for basic metabolism (carbohydrate metabolism, citrate cycle) and a decrease in the oxidative stress (riboflavin, sulfur, cysteine) as well as bacterial pathogenesis (cell motility and secretion, bacterial motility proteins, flagellar assembly). Moreover, a higher proportion of was observed in the SASP group, which may associate with infertility. In all, the study provides insight into specific microbial clades and pathways linked with SASP treatment to elaborate the mechanism for treatment of IBD.
炎症性肠病(IBD)是由肠道菌群和免疫系统的改变引起的。柳氮磺胺吡啶(SASP)是一种磺胺类抗菌药物,多年来一直在临床上用于治疗IBD。然而,SASP如何影响肠道微生物及其潜在功能仍不清楚。为了研究SASP、IBD和肠道微生物群之间的关系,我们用2,4,6-三硝基苯磺酸(TNBS)诱导大鼠实验性结肠炎,并通过16S基因测序分析来自对照组(用乙醇+生理盐水处理)、模型组(用TNBS-乙醇+生理盐水处理)和SASP组(用TNBS-乙醇+SASP处理)的粪便样本中的微生物群,并用鸟枪法测序对一部分样本进行了随访。研究发现,SASP治疗不仅可以恢复TNBS诱导的肠道菌群失调,这通过产生短链脂肪酸的细菌和产生乳酸的细菌数量增加以及变形菌数量减少得到证明,还可以调节TNBS诱导的结肠炎失调的功能,使其类似于对照组,包括基础代谢(碳水化合物代谢、柠檬酸循环)能力增加、氧化应激(核黄素、硫、半胱氨酸)减少以及细菌致病机制(细胞运动和分泌、细菌运动蛋白、鞭毛组装)降低。此外,在SASP组中观察到较高比例的 ,这可能与不孕有关。总之,该研究深入了解了与SASP治疗相关的特定微生物类群和途径,以阐明治疗IBD的机制。