评估微生物和万古霉素治疗在溃疡性结肠炎的小鼠模型中的作用。

BACKGROUND: Despite the number of available therapies for ulcerative colitis (UC), severe side effects and high cost has limited their clinical application. Thus, finding new alternative strategies with minimal side effects is inevitable. Therefore, this study aimed to compare the effectiveness of different therapeutic approaches in DSS-induced colitis. METHODS: Firstly, we designed oral bio-therapeutic products, Live Bacterial Products (LBP), which include a mixture of fecal bacteria strains isolated from healthy mice and prepared by microencapsulation and freeze-dried techniques. Then we investigated the efficiency of 7 days of freeze-dried FMT, LBP, and vancomycin treatments in DSS-induced colitis. Secondly, we compared the effect of 15 days of microbial therapies (freeze-dried powder of FMT and LBP microcapsules) and seven days of oral vancomycin on the severity of colitis in mice. Furthermore, the levels of IL-1β and TNF-α were measured in serum by ELISA, and the fecal microbiota diversity was analyzed by high-throughput sequencing for all mice groups. RESULTS: After seven days of treatments, our results indicated that oral vancomycin reduced the severity of DSS-induced colitis in mice, where weight gain and a decrease in IL-1 β and TNF-α levels were observed in the vancomycin group compared with other treatment groups. While after two weeks of treatment, the LBP microcapsules were able to reduce the severity of colitis. And at the end of the treatment period, weight gain and a decrease in the DAI scores and the levels of IL-1β and TNF-α were noted in the LBP treatment group compared to other treatment groups. By high-throughput sequencing of the 16S rRNA gene, our results showed that while the microcapsules LBP treatment increased the fecal microbial diversity, after vancomycin therapy, most of the fecal microbiota genera and operational taxonomic units (OTUs) were depleted. CONCLUSION: Our results concluded that treatment duration and preparation methods affect the microbial therapies' efficiency in UC. Furthermore, this study highlighted the negative consequences of oral vancomycin administration on gut health that should be known before using this medication.

背景：尽管溃疡性结肠炎（UC）有多种治疗方法，但严重的副作用和高昂的成本限制了它们的临床应用。因此，寻找副作用最小的新替代策略是不可避免的。因此，本研究旨在比较不同治疗方法在 DSS 诱导的结肠炎中的疗效。

方法：首先，我们设计了口服生物治疗产品，即活菌产品（LBP），它包括从健康小鼠中分离出的粪便细菌菌株混合物，并通过微囊化和冷冻干燥技术制备。然后，我们研究了 7 天冷冻干燥 FMT、LBP 和万古霉素治疗在 DSS 诱导的结肠炎中的疗效。其次，我们比较了 15 天微生物治疗（FMT 冷冻干燥粉和 LBP 微胶囊）和 7 天口服万古霉素对小鼠结肠炎严重程度的影响。此外，通过 ELISA 测量所有小鼠组的血清中 IL-1β 和 TNF-α 水平，并通过高通量测序分析粪便微生物多样性。

结果：经过 7 天的治疗，我们的结果表明，口服万古霉素可减轻 DSS 诱导的结肠炎小鼠的严重程度，与其他治疗组相比，万古霉素组体重增加，IL-1β 和 TNF-α 水平降低。而两周的治疗后，LBP 微胶囊能够减轻结肠炎的严重程度。在治疗结束时，与其他治疗组相比，LBP 治疗组体重增加，DAI 评分和 IL-1β 和 TNF-α 水平降低。通过 16S rRNA 基因高通量测序，我们的结果表明，虽然 LBP 微胶囊治疗增加了粪便微生物多样性，但万古霉素治疗后，大多数粪便微生物属和操作分类单元（OTUs）被消耗殆尽。

结论：我们的研究结果表明，治疗时间和制备方法会影响 UC 中微生物治疗的效果。此外，本研究强调了口服万古霉素治疗对肠道健康的负面影响，在使用这种药物之前应该了解这些负面影响。