肝硬化中的肠道微生物群与细胞因子谱

Gut Microbiota and Cytokine Profile in Cirrhosis.

作者信息

Efremova Irina, Maslennikov Roman, Kudryavtseva Anna, Avdeeva Anastasia, Krasnov George, Diatroptov Mikhail, Bakhitov Vyacheslav, Aliev Salekh, Sedova Natalia, Fedorova Maria, Poluektova Elena, Zolnikova Oxana, Aliev Nariman, Levshina Anna, Ivashkin Vladimir

机构信息

Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russia.

Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.

出版信息

J Clin Transl Hepatol. 2024 Aug 28;12(8):689-700. doi: 10.14218/JCTH.2024.00090. Epub 2024 Jun 28.

DOI:10.14218/JCTH.2024.00090

PMID:39130620

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11310756/

Abstract

BACKGROUND AND AIMS

Gut dysbiosis and abnormal cytokine profiles are common in cirrhosis. This study aimed to evaluate the correlations between them.

METHODS

In the blood plasma of cirrhosis patients and controls, 27 cytokines were examined using a multiplex assay. The plasma levels of nitrites (stable metabolites of the endothelial dysfunction biomarker nitric oxide) and lipopolysaccharide (LPS) were examined. The fecal microbiota was assessed by 16S rRNA gene sequencing.

RESULTS

Levels of IL-1b, IL-2, IL-6, IL-13, IP-10, IFN-g, TNF-a, LPS, and nitrites were higher in cirrhosis patients than in controls, while levels of IL-4, IL-7, and PDGF-BB were lower. The LPS level was directly correlated with the levels of IL-1b, IL1-Ra, IL-9, IL-17, PDGF-BB, IL-6, TNF-a, and nitrites. The nitrite level was significantly directly correlated with the levels of TNF-a, GM-CSF, IL-17, and IL-12, and inversely correlated with the IL-7 level. TNF-a levels were directly correlated with ascites severity and the abundance of Negativicutes, Enterobacteriaceae, Veillonellaceae, and Klebsiella, while inversely correlated with the abundance of Firmicutes, Clostridia, and Subdoligranulum. IFN-g levels were directly correlated with the abundance of Bacteroidaceae, Lactobacillaceae, Bacteroides, and Megasphaera, and inversely correlated with the abundance of Verrucomicrobiota, Akkermansiaceae, Coriobacteriaceae, Akkermansia, Collinsella, and Gemella. IL-1b levels were directly correlated with the abundance of Comamonadaceae and Enterobacteriaceae and inversely correlated with the abundance of Marinifilaceae and Dialister. IL-6 levels were directly correlated with the abundance of Enterobacteriaceae, hepatic encephalopathy, and ascites severity, and inversely correlated with the abundance of Peptostreptococcaceae, Streptococcaceae, and Streptococcus.

CONCLUSIONS

The abundance of harmful gut microbiota taxa and endotoxinemia directly correlates with the levels of proinflammatory cytokines.

摘要

背景与目的

肠道菌群失调和细胞因子谱异常在肝硬化患者中很常见。本研究旨在评估它们之间的相关性。

方法

使用多重检测法检测肝硬化患者和对照组血浆中的27种细胞因子。检测血浆中亚硝酸盐（内皮功能障碍生物标志物一氧化氮的稳定代谢产物）和脂多糖（LPS）的水平。通过16S rRNA基因测序评估粪便微生物群。

结果

肝硬化患者的IL-1β、IL-2、IL-6、IL-13、IP-10、IFN-γ、TNF-α、LPS和亚硝酸盐水平高于对照组，而IL-4、IL-7和PDGF-BB水平较低。LPS水平与IL-1β、IL1-Ra、IL-9、IL-17、PDGF-BB、IL-6、TNF-α和亚硝酸盐水平直接相关。亚硝酸盐水平与TNF-α、GM-CSF、IL-17和IL-12水平显著正相关，与IL-7水平负相关。TNF-α水平与腹水严重程度以及Negativicutes、肠杆菌科、韦荣球菌科和克雷伯菌属的丰度正相关，与厚壁菌门、梭菌纲和Subdoligranulum的丰度负相关。IFN-γ水平与拟杆菌科、乳杆菌科、拟杆菌属和巨球形菌属的丰度正相关，与疣微菌门、阿克曼氏菌科、棒状杆菌科、阿克曼氏菌、柯林斯菌属和孪生菌属的丰度负相关。IL-1β水平与丛毛单胞菌科和肠杆菌科的丰度正相关，与海栖菌科和戴阿李斯特菌属的丰度负相关。IL-6水平与肠杆菌科的丰度、肝性脑病和腹水严重程度正相关，与消化链球菌科、链球菌科和链球菌属的丰度负相关。