Department of Internal Medicine, Division of Infectious Diseases, University of Patras Medical School, 26504, Patras, Greece.
Department of Internal Medicine, Division of Gastroenterology, University of Patras Medical School, 26504, Patras, Greece.
Infection. 2018 Dec;46(6):751-760. doi: 10.1007/s15010-018-1178-5. Epub 2018 Jul 12.
Gut permeability is increased in critically ill patients, and associated with the development of the systemic inflammatory response syndrome and multiple organ dysfunction syndrome (MODS). The pathogenetic link(s) and potential therapies are an area of intense research over the last decades.
We thoroughly reviewed the literature on gut-origin sepsis and MODS in critically ill patients, with emphasis on the implicated pathophysiological mechanisms and therapeutic interventions.
Intestinal barrier failure leading to systemic bacterial translocation associated with MODS was the predominant pathophysiological theory for several years. However, clinical studies with critically ill patients failed to provide the evidence of systemic spread of gut-derived bacteria and/or their products as a cause of MODS. Newer experimental data highlight the role of the mesenteric lymph as a carrier of gut-derived danger-associated molecular patterns (DAMPs) to the lung and the systemic circulation. These substances are recognized by pattern recognition receptor-bearing cells in diverse tissues and promote proinflammatory pathways and the development MODS. Therefore, the gut becomes a pivotal proinflammatory organ, driving the systemic inflammatory response through DAMPs release in mesenteric lymph, without the need for systemic bacterial translocation.
There is an emerging need for application of sensitive non-invasive and easily measured biomarkers of early intestinal injury (e.g., citrulline, intestinal fatty acid protein, and zonulin) in our everyday clinical practice, guiding the early pharmacological intervention in critically ill patients to restore or prevent intestinal injury and improve their outcomes.
危重症患者的肠道通透性增加，与全身炎症反应综合征和多器官功能障碍综合征（MODS）的发生有关。在过去几十年中，其发病机制和潜在治疗方法一直是研究的热点。
我们全面回顾了关于危重症患者肠道来源性脓毒症和 MODS 的文献，重点关注相关的病理生理机制和治疗干预措施。
肠道屏障功能衰竭导致与 MODS 相关的全身细菌易位曾是多年来的主要病理生理理论。然而，针对危重症患者的临床研究未能提供肠道来源的细菌及其产物在 MODS 中的全身传播的证据。新的实验数据强调了肠系膜淋巴作为肠道来源的损伤相关分子模式（DAMPs）向肺部和全身循环的载体的作用。这些物质被多种组织中具有模式识别受体的细胞识别，并促进促炎途径和 MODS 的发展。因此，肠道成为一个关键的促炎器官，通过 DAMPs 在肠系膜淋巴中的释放引发全身炎症反应，而无需全身细菌易位。
在日常临床实践中，迫切需要应用敏感的、非侵入性的和易于测量的早期肠道损伤生物标志物（如瓜氨酸、肠脂肪酸结合蛋白和肠紧密连接蛋白），以指导危重症患者的早期药物干预，从而恢复或预防肠道损伤，改善其预后。
