Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea.
Laboratory Animal Experiment Center, Bionsystems, Uiwang-si, Gyeonggi-do, Republic of Korea.
Front Immunol. 2024 Oct 22;15:1451356. doi: 10.3389/fimmu.2024.1451356. eCollection 2024.
Restoring a balanced, healthy gut microbiota through fecal microbiota transplantation (FMT) has the potential to be a treatment option for sepsis, despite the current lack of evidence. This study aimed to investigate the effect of FMT on sepsis in relation to the gut microbiota through a sepsis model in juvenile mice.
Three-week-old male mice were divided into three groups: the antibiotic treatment (ABX), ABX-FMT, and control groups. The ABX and ABX-FMT groups received antibiotics for seven days. FMT was performed through oral gavage in the ABX-FMT group over the subsequent seven days. On day 14, all mice underwent cecal ligation and puncture (CLP) to induce abdominal sepsis. Blood cytokine levels and the composition of fecal microbiota were analyzed, and survival was monitored for seven days post-CLP.
Initially, the fecal microbiota was predominantly composed of the phyla Bacteroidetes and Firmicutes. After antibiotic intake, an extreme predominance of the class Bacilli emerged. FMT successfully restored antibiotic-induced fecal dysbiosis. After CLP, the phylum Bacteroidetes became extremely dominant in the ABX-FMT and control groups. Alpha diversity of the microbiota decreased after antibiotic intake, was restored after FMT, and decreased again following CLP. In the ABX group, the concentrations of interleukin-1β (IL-1β), IL-2, IL-6, IL-10, granulocyte macrophage colony-stimulating factor, tumor necrosis factor-α, and C-X-C motif chemokine ligand 1 increased more rapidly and to a higher degree compared to other groups. The survival rate in the ABX group was significantly lower (20.0%) compared to other groups (85.7%).
FMT-induced microbiota restoration demonstrated a protective effect against sepsis. This study uniquely validates the effectiveness of FMT in a juvenile mouse sepsis model, offering potential implications for clinical research in critically ill children.
通过粪便微生物群移植（FMT）恢复平衡、健康的肠道微生物群有可能成为脓毒症的治疗选择，尽管目前缺乏证据。本研究旨在通过幼鼠脓毒症模型研究 FMT 对肠道微生物群与脓毒症的关系。
将 3 周龄雄性小鼠分为三组：抗生素治疗（ABX）组、ABX-FMT 组和对照组。ABX 和 ABX-FMT 组接受 7 天的抗生素治疗。ABX-FMT 组在随后的 7 天内通过口服灌胃进行 FMT。第 14 天，所有小鼠接受盲肠结扎和穿刺（CLP）以诱导腹部脓毒症。分析血液细胞因子水平和粪便微生物群组成，并监测 CLP 后 7 天的存活情况。
最初，粪便微生物群主要由厚壁菌门和拟杆菌门组成。抗生素摄入后，芽孢杆菌纲的比例急剧增加。FMT 成功恢复了抗生素诱导的粪便菌群失调。CLP 后，ABX-FMT 和对照组的拟杆菌门变得极为占优势。抗生素摄入后微生物群的 alpha 多样性减少，FMT 后恢复，CLP 后再次减少。ABX 组中，白细胞介素-1β（IL-1β）、IL-2、IL-6、IL-10、粒细胞-巨噬细胞集落刺激因子、肿瘤坏死因子-α和 C-X-C 基序趋化因子配体 1 的浓度增加更快，程度更高。ABX 组的存活率（20.0%）明显低于其他组（85.7%）。
FMT 诱导的微生物群恢复对脓毒症具有保护作用。本研究独特地验证了 FMT 在幼鼠脓毒症模型中的有效性，为危重症儿童的临床研究提供了潜在意义。
