Disruption of gut barrier integrity and host-microbiome interactions underlie MASLD severity in patients with type-2 diabetes mellitus.
Disruption of gut barrier integrity and host-microbiome interactions underlie MASLD severity in patients with type-2 diabetes mellitus.
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DOI：
10.1080/19490976.2024.2304157
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发表时间：
2024-01
期刊：
影响因子：
12.2
通讯作者：
中科院分区：
文献类型：
--
作者：
“肠-肝轴”的异常参与了代谢功能障碍相关性脂肪性肝病(MASLD)的发生和发展。在这里，我们使用多组学来分析2型糖尿病(T2 DM)患者的肠道微生物区系组成和代谢特征。T2 DM患者通过血液测试、超声和肝脏硬度测量来筛查肝病。用16S rRNA基因测序分析粪便微生物区系，用核磁共振波谱和超高性能质谱仪分析代谢组谱。在整个队列和匹配的子集中分析微生物组和代谢特征，以确定脂肪变性(MASLD±)或纤维化(Fibrosis±)的特异性特征。用MDCK细胞单层和跨上皮电阻(TEER)测定肠通透性。检测血清和粪便中的细胞因子谱。总体而言，285名患者入选：255名血清、252名尿液和97份粪便样本被分析。在肝功能正常的患者中，厌氧菌和大肠埃希菌/志贺氏菌的ASV较高，而丁链球菌ASV较低。在MASLD±中，脂肪变性患者的Butyricicoccus ASV显著升高。在纤维化程度为±的患者中，肝纤维化患者的Butyricicoccus ASV显著降低。甘鹅脱氧胆酸-3-硫酸酯(G-UDCA-3S)在有纤维化的MASLD中似乎较高。来自MASLD和纤维化患者的粪便水导致的TEER比那些正常肝脏的患者下降最大；这一点被蛋白酶抑制剂逆转。最后，伴有纤维化的MASLD患者的粪便IL-13水平较低。我们确定了脂肪变性和纤维化的特异性微生物组特征，并独立于其他代谢危险因素。此外，我们得出结论，蛋白酶相关的肠道通透性在伴有纤维化的MASLD患者中发挥了作用，疾病的进展与至少部分独立于T2 DM的肠道-肝轴有关。
Aberration of the “gut-liver axis” contributes to the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we use multi-omics to analyze the gut microbiota composition and metabolic profile of patients with type-2 diabetes mellitus (T2DM). T2DM patients were screened for liver disease by blood tests, ultrasound, and liver stiffness measurements. Stool microbiota was analyzed by 16S rRNA gene sequencing; metabolomic profiling by Nuclear Magnetic Resonance spectroscopy and Ultra-High Performance-Mass Spectrometry. Microbiome and metabolic signatures were analyzed in the whole cohort and in matched subsets to identify signatures specific for steatosis (MASLD±) or fibrosis (Fibrosis±). Gut permeability was assessed in-vitro using monolayers of MDCK cells and trans-epithelial electric resistance (TEER). Cytokine profile was assessed in serum and stools. Overall, 285 patients were enrolled: 255 serum, 252 urine and 97 stool samples were analyzed. Anaeroplasma and Escherichia/Shigella ASVs were higher, while Butyricicoccus ASVs were lower in those with normal liver. In MASLD±, Butyricicoccus ASV was significantly higher in those with steatosis. In the Fibrosis±, Butyricicoccus ASV was significantly lower in those with fibrosis. Glycochenodeoxycholic acid-3-sulfate (G-UDCA-3S) appeared to be higher in MASLD with fibrosis. Fecal water from patients with MASLD and fibrosis caused the greatest drop in the TEER vs those with normal liver; this was reversed with protease inhibitors. Finally, fecal IL-13 was lower in MASLD with fibrosis. We identified microbiome signatures which were specific for steatosis and fibrosis and independent of other metabolic risk factors. Moreover, we conclude that protease-related gut permeability plays a role in those MASLD patients with fibrosis, and that disease progression is linked to a gut-liver axis which is at least partially independent of T2DM.
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影响因子：
8.4
作者：
Takis PG;Jiménez B;Sands CJ;Chekmeneva E;Lewis MR
通讯作者：
Lewis MR
DOI：
10.1111/liv.14696
发表时间：
2020-12
期刊：
Liver international : official journal of the International Association for the Study of the Liver
影响因子：
--
作者：
De Munck TJI;Xu P;Verwijs HJA;Masclee AAM;Jonkers D;Verbeek J;Koek GH
通讯作者：
Koek GH
DOI：
10.1016/j.jhepr.2021.100411
发表时间：
2022-01
期刊：
JHEP reports : innovation in hepatology
影响因子：
--
作者：
Anstee QM;Hallsworth K;Lynch N;Hauvespre A;Mansour E;Kozma S;Marino JP;Bottomley J;Piercy J;Higgins V
通讯作者：
Higgins V
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
2.4
作者：
Forlano R;Mullish BH;Dhar A;Goldin RD;Thursz M;Manousou P
通讯作者：
Manousou P