Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, PR China.
Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, PR China.
J Autoimmun. 2023 Dec;141:103109. doi: 10.1016/j.jaut.2023.103109. Epub 2023 Sep 9.
Autoimmune diseases (AIDs) are a series of immune-mediated lethal diseases featured by over-activated immune cells attacking healthy self-tissues and organs due to the loss of immune tolerance, which always causes severe irreversible systematical organ damage and threatens human health heavily. To date, there are still no definitive cures for the treatment of AIDs due to their pathogenesis has not been clearly understood. Besides, the current clinical treatments of AIDs majorly rely on glucocorticoids and immune suppressors, which can lead to serious side effects. In the past years, there are increasing studies demonstrating that an imbalance of gut microbiota is intimately related to the pathogenesis of various AIDs, shedding light on the development of therapeutics by targeting the gut microbiota for the management of AIDs. Among all the approaches targeting the gut microbiota, fecal microbiota transplantation (FMT) has attracted increasing interest, and it has been proposed as a possible strategy to intervene in the homeostasis of gut microbiota for the treatment of various diseases. However, despite the reported good curative effects and clinical studies conducted on FMT, the detailed mechanisms of FMT for the effective treatment of those diseases have not been figured out. To fully understand the mechanisms of the therapeutic effects of FMT on AIDs and improve the therapeutic efficacy of FMT treatment, a systematic review of this topic is necessary. Hence, in this review paper, the potential mechanisms of FMT for the treatment of various AIDs were summarized, including promotion, shaping, activation, or inhibition of the host immune system via the interactions between the microorganisms and the gut immune system, gut-brain, gut-liver, gut-kidney axis, and so on. Then, applications of FMT for the treatment of various AIDs were detailed presented. Finally, the current challenges and potential solutions for the development of FMT formulations and FMT therapeutics were comprehensively discussed.
自身免疫性疾病(AIDs)是一组由免疫细胞过度激活引起的免疫介导的致命性疾病,这些免疫细胞攻击健康的自身组织和器官,是由于免疫耐受的丧失,这通常会导致严重的不可逆转的系统性器官损伤,严重威胁人类健康。迄今为止,由于其发病机制尚不清楚,因此对于 AIDs 的治疗仍没有明确的治愈方法。此外,目前 AIDs 的临床治疗主要依赖于糖皮质激素和免疫抑制剂,这会导致严重的副作用。近年来,越来越多的研究表明,肠道微生物群的失衡与各种 AIDs 的发病机制密切相关,为通过靶向肠道微生物群来管理 AIDs 开发治疗方法提供了启示。在所有针对肠道微生物群的方法中,粪便微生物群移植(FMT)引起了越来越多的关注,它已被提出作为一种可能的策略来干预肠道微生物群的动态平衡,以治疗各种疾病。然而,尽管 FMT 已被报道具有良好的治疗效果,并进行了相关的临床研究,但 FMT 治疗这些疾病的详细机制仍未阐明。为了充分了解 FMT 治疗 AIDs 的治疗效果的机制,并提高 FMT 治疗的疗效,有必要对这一主题进行系统的综述。因此,在这篇综述文章中,总结了 FMT 治疗各种 AIDs 的潜在机制,包括通过微生物与肠道免疫系统、肠-脑、肠-肝、肠-肾轴等的相互作用促进、塑造、激活或抑制宿主免疫系统。然后详细介绍了 FMT 治疗各种 AIDs 的应用。最后,全面讨论了 FMT 制剂和 FMT 治疗学发展的当前挑战和潜在解决方案。