■尽管肠道炎症和生态失调与2019年冠状病毒病严重病例(COVID-19)的病理生理学有关,肠道抗炎酶的作用,如碱性磷酸酶,仍未充分开发。因此,本研究的目的是比较轻中度和重度COVID-19患者的肠道碱性磷酸酶(iALP)活性及其促炎底物-细菌脂多糖(LPS)浓度.
■从53名轻度至中度和57名重度成人COVID-19患者收集的粪便样本,以前参加过国家多中心横断面研究(NCT04355741),分析iALP活性和LPS浓度。
■在调整临床和肠道微生物参数后,与轻度至中度COVID-19患者相比,重度患者的iALP活性降低了40%(中位数[四分位距]120.6[25.2-593.1]nmolpNP/min/g蛋白质,而202.8[102.1-676.1]nmolpNP/min/g蛋白质;P=.04)。关于粪便LPS,在重症患者中发现其浓度降低(平均值±标准误差为18,118±1225EU/g粪便vs22,508±1203EU/g粪便;P=0.01),尽管该参数与血浆C反应蛋白水平无关(P=.08),全身性炎症的敏感生物标志物。相比之下,粪便ALP活性/LPS浓度比,iALP效率的指标,与轻中度COVID-19患者相比,重度患者增加(P=0.04)。
在严重COVID-19患者中发现的iALP动力学参数的变化可能代表了抵消与COVID-19严重程度相关的肠道稳态改变(例如炎症和菌群失调)的潜在机制。
UNASSIGNED: Although gut inflammation and dysbiosis have been implicated in the pathophysiology of severe cases of coronavirus disease 2019 (COVID-19), the role of intestinal anti-inflammatory enzymes, such as alkaline phosphatase, is still underexplored. Therefore, the aim of this study was to compare intestinal alkaline phosphatase (iALP) activity and its proinflammatory substrate - bacterial lipopolysaccharide (LPS) - concentration between mild-to-moderate and severe COVID-19 patients.
UNASSIGNED: Stool samples collected from 53 mild-to-moderate and 57 severe adult COVID-19 patients, previously enrolled in a national multicentre cross-sectional study (NCT04355741), were analysed for iALP activity and LPS concentration.
UNASSIGNED: iALP activity decreased by 40% in severe compared to mild-to-moderate COVID-19 patients (median [interquartile range] of 120.6 [25.2-593.1] nmol pNP/min/g of protein vs 202.8 [102.1-676.1] nmol pNP/min/g of protein; P = .04) after adjustment for clinical and gut microbiota parameters. Regarding fecal LPS, its concentration was found to be decreased in severe patients (mean ± standard error of mean of 18,118 ± 1225 EU/g of feces vs 22,508 ± 1203 EU/g of feces; P = .01), although this parameter did not correlate with plasma levels of C-reactive protein (P = .08), a sensitive biomarker of systemic inflammation. In contrast, fecal ALP activity / LPS concentration ratio, an indicator of iALP efficiency, was found to be increased in severe compared to mild-to-moderate COVID-19 patients (P = .04).
UNASSIGNED: Changes in iALP kinetic parameters found in severe COVID-19 patients may represent a potential mechanism to counterbalance alterations in gut homeostasis (eg inflammation and dysbiosis) associated with COVID-19 severity.