The fecal mycobiome in non-alcoholic fatty liver disease.
The fecal mycobiome in non-alcoholic fatty liver disease.
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DOI：
10.1016/j.jhep.2021.11.029
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发表时间：
2022-04
影响因子：
25.7
通讯作者：
Schnabl B
中科院分区：
文献类型：
--
作者：
Demir M;Lang S;Hartmann P;Duan Y;Martin A;Miyamoto Y;Bondareva M;Zhang X;Wang Y;Kasper P;Bang C;Roderburg C;Tacke F;Steffen HM;Goeser T;Kruglov A;Eckmann L;Stärkel P;Fouts DE;Schnabl B
调查肠-肝轴的研究主要集中在细菌上，而对共生真菌知之甚少。我们研究了非酒精性脂肪性肝病（NAFLD）患者的粪便真菌，并研究了它们在西方饮食诱导的脂肪性肝炎小鼠粪便微生物组人源化模型中的作用。我们对78名NAFLD患者、16名对照组和73名酒精使用障碍（AUD）患者的粪便样本进行了真菌内转录间隔物2测序。对17例对照和79例NAFLD患者的血液样本进行抗白色念珠菌IgG检测。Songbird是一种新颖的多项回归工具，用于研究真菌群落的变化。无菌小鼠定植于非酒精性脂肪性肝炎（NASH）患者的粪便中，喂食西方饮食20周，并用抗真菌两性霉素b治疗。非肥胖NASH或F2-F4纤维化的存在与明显的粪便真菌组特征相关。变化的特征是在NASH和F2-F4纤维化患者中毛霉/酿酒酵母（S. cerevisiae）的对数比增加。白色念珠菌/S。与非肥胖NAFL患者或对照组相比，非肥胖NASH患者的cerevisiae log-ratio明显更高。我们观察到NAFLD合并晚期纤维化患者的粪便菌群组成与AUD合并晚期纤维化患者相比有所不同。等离子anti-C。白色念珠菌IgG在NAFLD合并晚期纤维化患者中升高。用人类NASH粪便定植并用两性霉素B治疗的无糖生物小鼠可预防西方饮食诱导的脂肪性肝炎。病情较晚期的非肥胖NAFLD患者粪便菌群组成与病情较轻的非肥胖NAFLD患者不同。抗真菌治疗可改善小鼠饮食诱导的脂肪性肝炎。肠道真菌可能是减轻NASH的一个有吸引力的靶点。非酒精性脂肪性肝病是最常见的慢性肝病之一，与粪便细菌微生物群的变化有关。我们发现，患有非酒精性脂肪性肝病和更严重的疾病阶段的患者有特定的粪便真菌组成和对白色念珠菌增加的全身免疫反应。在粪便微生物人源化小鼠模型的西方饮食诱导脂肪性肝炎，我们表明抗真菌治疗减少肝损伤。
Studies investigating the gut-liver axis have largely focused on bacteria, whereas little is known about commensal fungi. We characterized fecal fungi in patients with non-alcoholic fatty liver disease (NAFLD) and investigated their role in a fecal microbiome-humanized mouse model of Western diet-induced steatohepatitis. We performed fungal internal transcribed spacer 2 sequencing using fecal samples from 78 NAFLD patients, 16 controls and 73 patients with alcohol use disorder (AUD). Anti-Candida albicans (C. albicans) IgG was measured in blood samples from 17 controls and 79 NAFLD patients. Songbird, a novel multinominal regression tool, was used to investigate mycobiome changes. Germ-free mice were colonized with feces from patients with non-alcoholic steatohepatitis (NASH), fed a Western diet for 20 weeks and treated with the anti-fungal amphotericin B. The presence of non-obese NASH or F2-F4 fibrosis was associated with a distinct fecal mycobiome signature. Changes were characterized by an increased log-ratio for Mucor sp./Saccharomyces cerevisiae (S. cerevisiae) in patients with NASH and F2-F4 fibrosis. The C. albicans/S. cerevisiae log-ratio was significantly higher in non-obese patients with NASH when compared with non-obese patients with NAFL or controls. We observed a different fecal mycobiome composition in NAFLD patients with advanced fibrosis as compared with AUD patients and advanced fibrosis. Plasma anti-C. albicans IgG was increased in NAFLD patients with advanced fibrosis. Gnotobiotic mice, colonized with human NASH feces and treated with amphotericin B were protected from Western diet-induced steatohepatitis. Non-obese NAFLD patients with more advanced disease have a different fecal mycobiome composition than non-obese NAFLD patients with mild disease. Antifungal treatment ameliorates diet-induced steatohepatitis in mice. Intestinal fungi could be an attractive target to attenuate NASH. Non-alcoholic fatty liver disease is one of the most common chronic liver diseases and is associated with changes in the fecal bacterial microbiome. We show that patients with non-alcoholic fatty liver disease and more severe disease stages have a specific composition of fecal fungi and an increased systemic immune response to Candida albicans. In a fecal microbiome-humanized mouse model of Western-diet induced steatohepatitis, we show that treatment with antifungals reduces liver damage.
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影响因子：
16.6
作者：
Lee G;You HJ;Bajaj JS;Joo SK;Yu J;Park S;Kang H;Park JH;Kim JH;Lee DH;Lee S;Kim W;Ko G
通讯作者：
Ko G
影响因子：
24.5
作者：
Wong, Vincent Wai-Sun;Wong, Grace Lai-Hung;Chan, Henry Lik-Yuen
通讯作者：
Chan, Henry Lik-Yuen
DOI：
10.1007/s10096-013-1953-2
发表时间：
2014-02-01
影响因子：
4.5
作者：
Hwang, S. Y.;Yu, S. J.;Lee, H. -S.
通讯作者：
Lee, H. -S.
影响因子：
4.8
作者：
van der Merwe, Marie;Sharma, Sunita;Pierre, Joseph F.
通讯作者：
Pierre, Joseph F.
影响因子：
6.9
作者：
Miranda, L. N.;van der Heijden, I. M.;Levin, A. S.
通讯作者：
Levin, A. S.