Activation of the gut microbiota-kynurenine-liver axis contributes to the development of nonalcoholic hepatic steatosis in nondiabetic adults.
Activation of the gut microbiota-kynurenine-liver axis contributes to the development of nonalcoholic hepatic steatosis in nondiabetic adults.
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肠道微生物群-犬尿氨酸-肝轴的激活有助于非糖尿病成人非酒精性肝脂肪变性的发生
DOI：
10.18632/aging.203460
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发表时间：
2021-09-02
期刊：
影响因子：
--
通讯作者：
Yang G
中科院分区：
文献类型：
--
作者：
Sui G;Jia L;Quan D;Zhao N;Yang G
肠道-肝脏信号传导对非糖尿病成人非酒精性肝脂肪变性（NHS）发展的贡献仍不清楚。因此，我们在32名对照和59名NHS非糖尿病成人中进行了全面的16 S核糖体RNA测序和粪便代谢组学分析，并使用对照和NHS患者作为供体将粪便微生物群移植到无菌小鼠中。与对照组相比，在NHS受试者中，Collinsella和不动杆菌属的丰度较高，而毛螺菌属的丰度较低。粪便代谢组学分析显示，NHS患者的L-色氨酸水平降低，色氨酸代谢物犬尿氨酸丰度增加。相关分析表明犬尿氨酸水平与大肠杆菌属和不动杆菌属的丰度呈正相关。ROC分析表明，色氨酸和犬尿氨酸的组合可以区分NHS患者和对照组，具有良好的统计功效[P < 0.05; AUC = 0.833（95%CI，0.747至0.918）]。支持生态失调的肠道微生物群在NHS发展中的关键作用，在用来自NHS患者的样品定殖的GF小鼠中观察到初期肝脂肪变性和增加的犬尿氨酸水平。这些结果表明，由肠道微生物群组成改变引起的犬尿氨酸产生增强有助于非糖尿病成人的NHS，并表明色氨酸代谢物作为诊断生物标志物的相关性。
The contribution of gut-liver signaling to the development of non-alcoholic hepatic steatosis (NHS) in non-diabetic adults remains unclear. We therefore performed comprehensive 16S ribosomal RNA sequencing and fecal metabolomics analyses in 32 controls and 59 non-diabetic adults with NHS and performed fecal microbiota transplantation into germ-free mice using controls and NHS patients as donors. Compared to controls, the abundance of the genera Collinsella and Acinetobacter were higher, while that of Lachnospira was lower, in NHS subjects. Fecal metabolomics analysis showed decreased L-tryptophan levels and increased abundance of the tryptophan metabolite kynurenine in individuals with NHS. Correlation analysis showed that kynurenine levels positively associated with the abundance of Collinsella and Acinetobacter. ROC analysis demonstrated that the combination of tryptophan and kynurenine could discriminate NHS patients from controls with good statistical power [P < 0.05; AUC = 0.833 (95% CI, 0.747 to 0.918)]. Supporting a key role of dysbiotic gut microbiota in NHS development, incipient hepatic steatosis and increased kynurenine levels were observed in GF mice colonized with samples from NHS patients. These results indicate that enhanced kynurenine production resulting from altered gut microbiota composition contributes to NHS in nondiabetic adults and suggest the relevance of tryptophan metabolites as diagnostic biomarkers.
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影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
肠道菌群衍生的色氨酸代谢产物调节肝细胞和巨噬细胞中的炎症反应。
影响因子：
8.8
作者：
Krishnan S;Ding Y;Saedi N;Choi M;Sridharan GV;Sherr DH;Yarmush ML;Alaniz RC;Jayaraman A;Lee K
通讯作者：
Lee K
DOI：
10.1126/science.aam9949
发表时间：
2017-08-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Byndloss MX;Olsan EE;Rivera-Chávez F;Tiffany CR;Cevallos SA;Lokken KL;Torres TP;Byndloss AJ;Faber F;Gao Y;Litvak Y;Lopez CA;Xu G;Napoli E;Giulivi C;Tsolis RM;Revzin A;Lebrilla CB;Bäumler AJ
通讯作者：
Bäumler AJ
影响因子：
24
作者：
Cheng, Mei-Ling;Wang, Chao-Hung;Yang, Ning-I
通讯作者：
Yang, Ning-I
影响因子：
13.5
作者：
Alferink, Louise J. M.;Radjabzadeh, Djawad;Darwish Murad, Sarwa
通讯作者：
Darwish Murad, Sarwa