DataSheet_1_Fecal bacteria-free filtrate transplantation is proved as an effective way for the recovery of radiation-induced individuals in mice.docx

BackgroundIonizing radiation can cause intestinal microecological dysbiosis, resulting in changes in the composition and function of gut microbiota. Altered gut microbiota is closely related to the development and progression of radiation-induced intestinal damage. Although microbiota-oriented therapeutic options such as fecal microbiota transplantation (FMT) have shown some efficacy in treating radiation toxicity, safety concerns endure. Therefore, fecal bacteria-free filtrate transplantation (FFT), which has the potential to become a possible alternative therapy, is well worth investigating. Herein, we performed FFT in a mouse model of radiation exposure and monitored its effects on radiation damage phenotypes, gut microbiota, and metabolomic profiles to assess the effectiveness of FFT as an alternative therapy to FMT safety concerns.
ResultsFFT treatment conferred radioprotection against radiation-induced toxicity, representing as better intestinal integrity, robust proinflammatory and anti-inflammatory cytokines homeostasis, and accompanied by significant shifts in gut microbiome. The bacterial compartment of recipients following FFT was characterized by an enrichment of radioprotective microorganisms (members of family Lachnospiraceae). Furthermore, metabolome data revealed increased levels of microbially generated short-chain fatty acids (SCFAs) in the feces of FFT mice.
ConclusionsFFT improves radiation-induced intestinal microecological dysbiosis by reshaping intestinal mucosal barrier function, gut microbiota configurations, and host metabolic profiles, highlighting FFT regimen as a promising safe alternative therapy for FMT is effective in the treatment of radiation intestinal injury.

研究背景：电离辐射（Ionizing radiation）可引发肠道微生态失调（intestinal microecological dysbiosis），导致肠道菌群（gut microbiota）的组成与功能发生改变。肠道菌群失衡与辐射诱导肠损伤（radiation-induced intestinal damage）的发生发展密切相关。尽管以菌群为导向的治疗手段（如粪菌移植（Fecal Microbiota Transplantation, FMT））在缓解辐射毒性（radiation toxicity）方面已展现出一定疗效，但安全性顾虑依然存在。因此，有望成为潜在替代疗法的无菌滤液粪菌移植（Fecal Bacteria-Free Filtrate Transplantation, FFT）值得深入探究。本研究在辐射暴露小鼠模型中实施FFT干预，监测其对辐射损伤表型（radiation damage phenotypes）、肠道菌群及代谢组谱（metabolomic profiles）的影响，以评估FFT作为解决FMT安全性顾虑的替代疗法的有效性。研究结果：FFT干预可发挥辐射防护（radioprotection）作用，对抗辐射诱导的毒性，具体表现为肠道完整性（intestinal integrity）更佳、促炎与抗炎细胞因子稳态（cytokines homeostasis）维持良好，同时伴随肠道菌群结构（gut microbiome）发生显著改变。FFT受体小鼠的细菌菌群以辐射保护性微生物（毛螺菌科（Lachnospiraceae）的成员）富集为特征。此外，代谢组学数据显示，FFT干预小鼠粪便中微生物衍生的短链脂肪酸（Short-Chain Fatty Acids, SCFAs）水平显著升高。研究结论：FFT可通过重塑肠黏膜屏障功能（intestinal mucosal barrier function）、肠道菌群结构与宿主代谢谱（host metabolic profiles），改善辐射诱导的肠道微生态失调；鉴于FMT在辐射性肠损伤治疗中已展现有效性，FFT方案是一种极具潜力的安全替代疗法。