Section of General Surgery, Department of Surgery, University of Chicago, Chicago, Illinois.
Section of Trauma and Acute Care Surgery, Department of Surgery, University of Chicago, Chicago, Illinois.
Transl Res. 2020 Dec;226:12-25. doi: 10.1016/j.trsl.2020.07.002. Epub 2020 Jul 7.
Sepsis is defined as a dysregulated inflammatory response, which ultimately results from a perturbed interaction of both an altered immune system and the biomass and virulence of involved pathogens. This response has been tied to the intestinal microbiota, as the microbiota and its associated metabolites play an essential role in regulating the host immune response to infection. In turn, critical illness as well as necessary health care treatments result in a collapse of the intestinal microbiota diversity and a subsequent loss of health-promoting short chain fatty acids, such as butyrate, leading to the development of a maladaptive pathobiome. These perturbations of the microbiota contribute to the dysregulated immune response and organ failure associated with sepsis. Several case series have reported the ability of fecal microbiota transplant (FMT) to restore the host immune response and aid in recovery of septic patients. Additionally, animal studies have revealed the mechanism of FMT rescue in sepsis is likely related to the ability of FMT to restore butyrate producing bacteria and alter the innate immune response aiding in pathogen clearance. However, several studies have reported lethal complications associated with FMT, including bacteremia. Therefore, FMT in the treatment of sepsis is and should remain investigational until a more detailed mechanism of how FMT restores the host immune response in sepsis is determined, allowing for the development of more fine-tuned microbiota therapies.
脓毒症定义为一种失调的炎症反应,它最终源于免疫系统的改变和相关病原体的生物量和毒力之间的失调相互作用。这种反应与肠道微生物群有关,因为微生物群及其相关代谢物在调节宿主对感染的免疫反应方面起着至关重要的作用。反过来,严重疾病以及必要的医疗保健治疗会导致肠道微生物群多样性的崩溃和随后失去促进健康的短链脂肪酸,如丁酸盐,从而导致适应性不良的病理生物群落的发展。这些微生物群的扰动导致与脓毒症相关的失调免疫反应和器官衰竭。有几项病例系列报告称,粪便微生物群移植(FMT)能够恢复宿主的免疫反应并帮助脓毒症患者康复。此外,动物研究表明,FMT 在脓毒症中的拯救机制可能与 FMT 恢复产生丁酸盐的细菌和改变先天免疫反应以帮助清除病原体的能力有关。然而,有几项研究报告了与 FMT 相关的致命并发症,包括菌血症。因此,在确定 FMT 如何恢复脓毒症中宿主免疫反应的更详细机制之前,FMT 在脓毒症治疗中的应用仍然是研究性的,这允许开发更精细的微生物群治疗方法。