Araújo João R, Serafim Thainá, Ismael Shámila, Calhau Conceição, Faria Ana, Teixeira Diana
Nutrition & Metabolism Department, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal.
Nutrition & Metabolism, CINTESIS@RISE, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal.
Gastro Hep Adv. 2023 Jul 17;2(7):911-917. doi: 10.1016/j.gastha.2023.07.003. eCollection 2023.
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.
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.
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; = .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; = .01), although this parameter did not correlate with plasma levels of C-reactive protein ( = .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 ( = .04).
Changes in iALP kinetic parameters found in severe COVID-19 patients may represent a potential mechanism to counterbalance alterations in gut homeostasis ( inflammation and dysbiosis) associated with COVID-19 severity.
尽管肠道炎症和微生物群失调与2019冠状病毒病（COVID-19）重症病例的病理生理学有关，但肠道抗炎酶（如碱性磷酸酶）的作用仍未得到充分研究。因此，本研究的目的是比较轻至中度和重度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）的浓度。
对53例轻至中度和57例重度成年COVID-19患者的粪便样本进行分析，这些患者之前参加了一项全国多中心横断面研究（NCT04355741），检测其中iALP活性和LPS浓度。这些患者的粪便样本此前已被收集。
在调整临床和肠道微生物群参数后，重度COVID-19患者的iALP活性比轻至中度患者降低了40%（中位数[四分位间距]分别为120.6[25.2 - 593.1]nmol对硝基苯酚/分钟/克蛋白质和202.8[102.1 - 676.1]nmol对硝基苯酚/分钟/克蛋白质；P = 0.04）。关于粪便LPS，重度患者的浓度降低（平均±平均标准误分别为18,118±1225内毒素单位/克粪便和22,508±1203内毒素单位/克粪便；P = 0.01），尽管该参数与全身炎症的敏感生物标志物血浆C反应蛋白水平无相关性（P = 0.08）。相比之下，粪便ALP活性/LPS浓度比值（iALP效率指标）在重度COVID-19患者中比轻至中度患者升高（P = 0.04）。
重度COVID-19患者中发现的iALP动力学参数变化可能是一种潜在机制，以平衡与COVID-19严重程度相关的肠道稳态改变（炎症和微生物群失调）。
