Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 Mexico City, Mexico.
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 Mexico City, Mexico.
Biomed Pharmacother. 2021 Sep;141:111890. doi: 10.1016/j.biopha.2021.111890. Epub 2021 Jul 3.
The complex pathophysiology of sepsis makes it a syndrome with limited therapeutic options and a high mortality rate. Gram-negative bacteria containing lipopolysaccharides (LPS) in their outer membrane correspond to the most common cause of sepsis. Since the gut is considered an important source of LPS, intestinal damage has been considered a cause and a consequence of sepsis. Although important in the maintenance of the intestinal epithelial cell homeostasis, the microbiota has been considered a source of LPS. Recent studies have started to shed light on how sepsis is triggered by dysbiosis, and an increased inflammatory state of the intestinal epithelial cells, expanding the understanding of the gut-liver axis in sepsis. Here, we review the gut-liver interaction in Gram-negative sepsis, exploring the mechanisms of LPS inactivation, including the recently described contribution of an isoform of the cholesteryl-ester transfer protein (CETPI). Although several key questions remain to be answered when the pathophysiology of sepsis is reviewed, new contributions coming to light exploring the way LPS might be inactivated in vivo, suggest that new applications might soon reach the clinical setting.
脓毒症的复杂病理生理学使其成为一种治疗选择有限且死亡率高的综合征。革兰氏阴性菌的外膜含有脂多糖（LPS），是脓毒症最常见的病因。由于肠道被认为是 LPS 的重要来源，肠道损伤被认为是脓毒症的一个原因和结果。尽管在维持肠道上皮细胞稳态方面很重要，但微生物群已被认为是 LPS 的来源。最近的研究开始阐明脓毒症如何由菌群失调和肠道上皮细胞炎症状态增加引发，从而扩展了对脓毒症中肠-肝轴的理解。在这里，我们综述革兰氏阴性菌脓毒症中的肠-肝相互作用，探讨 LPS 失活的机制，包括最近描述的胆固醇酯转移蛋白（CETPI）同工型的贡献。尽管在综述脓毒症的病理生理学时仍有几个关键问题有待解答，但新的研究结果表明，体内 LPS 可能失活的方式，提示新的应用可能很快会进入临床实践。
