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★   摘要 Abstract 肠道微生物群在健康和疾病中起着至关重要的作用。肠道微生物群会持续演变，并且会与其宿主保持持续的交流。肠道微生物群越来越多地被视为一个器官，其以菌群失调为表现的功能衰竭，也被认为是一种器官衰竭，与预后不良密切相关。危重患者的肠道微生物群可发生改变，即菌群失调，其中“对健康有益”的共生肠道细菌（如厚壁菌或拟杆菌）严重减少，潜在的致病细菌（如变形杆菌）则增加。危重患者中出现的许多因素都会增加菌群失调的风险，如药物治疗或营养支持模式的改变。菌群失调则会产生一些重要的影响，包括肠道完整性的改变和代谢产物（如短链脂肪酸和三甲胺氧化物等）的改变。越来越多的证据表明，肠道微生物群及其变化与其他器官会产生交互作用，突出了肠道-器官轴的概念。因此，肠道微生物群失调将影响其他器官，并可能影响重症疾病的进展。目前对肠道微生物群的了解才刚起步，尚有许多相关知识有待发现。肠道微生物群的确切作用和贡献及其与各种器官的相互作用是一个急切而富有挑战性的研究领域，为疾病预防、管理和治疗提供了令人兴奋的机会，特别是在常以多器官衰竭为焦点的重症监护领域中。本文概述了肠道微生物群的正常组成、功能、导致菌群失调的机制及其在重症监护环境中的作用，并强调了肠道-器官轴的概念。 Gut microbiota plays an essential role in health and disease. It is constantly evolving and in permanent communica‑tion with its host. The gut microbiota is increasingly seen as an organ, and its failure, refected by dysbiosis, is seen as an organ failure associated with poor outcomes. Critically ill patients may have an altered gut microbiota, namely dysbiosis, with a severe reduction in “health-promoting” commensal intestinal bacteria (such as Firmicutes or Bacte‑roidetes) and an increase in potentially pathogenic bacteria (e.g. Proteobacteria). Many factors that occur in critically ill patients favour dysbiosis, such as medications or changes in nutrition patterns. Dysbiosis leads to several important efects, including changes in gut integrity and in the production of metabolites such as short-chain fatty acids and trimethylamine N-oxide. There is increasing evidence that gut microbiota and its alteration interact with other organs, highlighting the concept of the gut–organ axis. Thus, dysbiosis will afect other organs and could have an impact on the progression of critical diseases. Current knowledge is only a small part of what remains to be discovered. The pre‑cise role and contribution of the gut microbiota and its interactions with various organs is an intense and challenging research area that ofers exciting opportunities for disease prevention, management and therapy, particularly in criti‑cal care where multi-organ failure is often the focus. This narrative review provides an overview of the normal compo‑sition of the gut microbiota, its functions, the mechanisms leading to dysbiosis, its consequences in an intensive care setting, and highlights the concept of the gut–organ axis. 脓毒症与微生物群 Sepsis and microbiota 许多重症监护患者存在严重感染。尽管具体机制尚未完全明确，但肠道微生物群似乎在脓毒症的病理生理学中起着一定的作用。部分原因是危重患者经常接受多种药物治疗，影响肠道微生物群多样性；部分原因是患者病情不稳定，可导致肠道缺氧损伤、炎症、上皮完整性破坏、运动功能障碍、肠内pH变化或免疫功能受损。一些肠道微生物群的特征性模式也与脓毒症有关。一项多中心研究发现，重症监护中患有脓毒症患者的微生物群显示与炎症密切相关的微生物数量增加，如副杆菌、梭形杆菌和嗜双歧杆菌。其他研究发现，肠道失去了重要的细菌属，包括粪杆菌属、普氏杆菌属、布氏菌属和瘤胃球菌属，众所周知，这些菌属会产生短链脂肪酸。此外，研究表明，某些抗生素耐药菌属在脓毒症中普遍存在，如肠球菌或梭状芽孢菌属，与预后不良密切相关。目前认为，肠道微生物群对脓毒症的影响，不仅通过细菌易位和防止多重耐药病原体的定植，也通过免疫系统的调节产生影响。实验室数据显示，与健康小鼠相比，在患脓毒症期间，无菌小鼠的细菌传播更广泛，炎症反应和器官衰竭更严重，死亡率更高，这可能是免疫调节反应不太明显所致。 Numerous ICU patients have severe infections. Although the specifc mechanisms are not yet fully identifed, the gut microbiota appears to play a role in the pathophysiology of sepsis. Tis is partly due to the fact that critically ill patients often receive a wide range of medications, which afect gut microbiota diversity , and partly because of the patients’ precarious condition, which can lead to hypoxic lesions, infammation, disruption of epithelial integrity, dysmotility, changes in intraluminal pH or impaired immune function in the gut. Tere are some characteristic patterns of gut microbiota associated with sepsis. In a multicentre study, the microbiota of ICU patients with sepsis showed an increased abundance of microbes closely associated with infammation, such as Parabacteroides, Fusobacterium and Bilophila species. Other studies showed that the gut loses important bacterial genera, including Faecalibacteriumspp., Prevotella spp., Blautia spp. and Ruminococcaceaespp., which are known to produce SCFAs. Furthermore, it has been shown that certain antibioticresistant species prevalent in sepsis, such as Enterococcusspp. or Clostridia spp., are associated with unfavourable outcomes. Te gut microbiota is thought to infuence sepsis not only through bacterial translocation and through the prevention of colonization by multi-resistant pathogens , but also by regulating the immune system . Laboratory data show greater bacterial spread, higher levels of infammation and organ failure, and higher mortality in germ-free mice during sepsis compared to healthy mice, likely due to a less pronounced immunomodulatory response. 结论 Conclusion 肠道微生物群与我们机体的重要器官保持着持续的交流，并对其产生强烈影响。根据最新证据，肠道微生物群可被视为一种器官，其功能衰竭（表现为菌群失调）可被认为是一种器官衰竭，可能与临床预后不良有关。肠道微生物群的确切作用和贡献及其与各种器官的相互作用是一个急切而富有挑战性的研究领域，还有许多未解之谜有待发现。另一个不应忽视的方面是，肠道微生物群的组成，受遗传因素和非遗传因素（如生活方式、饮食）影响，也受疾病及其治疗影响。目前对肠道微生物群的进一步研究还亟待解决，以更好地了解上述过程，为疾病预防、管理和治疗提供新的机会，尤其为以多器官衰竭为焦点的重症监护提供新的机会。 Te gut microbiota is in constant communication with key organs of our organism and strongly infuences them. According to the latest evidence, gut microbiota could be considered as an organ and its failure, manifested by dysbiosis, as an organ failure, which is possibly associated with poor clinical outcomes. Te exact roles and contributions of the gut microbiota and its interactions with the various organs are an intense and challenging area of research, and much remains to be discovered. Another aspect that should not be neglected is that the composition of the gut microbiota is infuenced by genetic and non-genetic factors such as lifestyle, diet, but also by diseases and their treatments. Further research on the gut microbiota is needed to better understand these processes, and to ofer new opportunities for disease prevention, management and therapy, especially in critical care where multi-organ failure is often the focus. 参考文献 Wozniak,H.,Beckmann,T.S.,Fröhlich,L.et al. The central and biodynamic role of gut microbiota in critically ill patients. Crit Care 26, 250 (2022). DOI:https:///10.1186/s13054-022-04127-5 译者简介  李宇娜 郑州大学第一附属医院 呼吸ICU住院医师 医学博士
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