Dynamic Changes of the Fungal Microbiome in Alcohol Use Disorder.

Dynamic Changes of the Fungal Microbiome in Alcohol Use Disorder.
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DOI:
10.3389/fphys.2021.699253
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发表时间:
2021
影响因子:
4
通讯作者:
Schnabl B
Schnabl B
中科院分区:
医学2区
文献类型:
--
作者:
Hartmann P;Lang S;Zeng S;Duan Y;Zhang X;Wang Y;Bondareva M;Kruglov A;Fouts DE;Stärkel P;Schnabl B

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酒精相关性肝病(ALD)是全世界发病和死亡的重要原因。肠道菌群参与 ALD 的发生和进展;然而,人们对其中的共生真菌知之甚少。我们使用粪便样本的内转录间隔区 2 (ITS2) 扩增子测序,研究了 66 名酒精使用障碍 (AUD) 患者和戒酒 2 周后肠道真菌微生物组或真菌组的动态变化。与对照受试者相比,AUD 患者的念珠菌属、德巴利酵母属、毕赤酵母属、克鲁维酵母属和伊萨琴基酵母属以及白色念珠菌和泽兰诺德念珠菌属的丰度显着增加。戒酒两周后,AUD 患者的肝脏健康标志物半胱天冬酶裂解和完整细胞角蛋白 18 (CK18-M65) 水平和受控衰减参数 (CAP) 显着改善,与念珠菌属、马拉色菌属、毕赤酵母属、克鲁维酵母属、伊萨琴基氏菌属以及白色念珠菌和 zeylanoides 念珠菌属丰度显着降低相关。这反映在显着更高的特异性抗 C 抗体上。与对照参与者相比,AUD 患者的白色念珠菌免疫球蛋白 G (IgG) 和 M (IgM) 血清水平显着降低,并且抗 C 蛋白显着降低。禁欲 2 周后 AUD 受试者的白色念珠菌 IgG 水平。与非进行性肝病相比,患有进行性肝病的 AUD 受试者肠道中马拉色菌属的丰度显着更高。总之,AUD 患者戒酒后肝脏健康状况的改善与肠道念珠菌和马拉色菌丰度的降低以及血清抗 C 抗体的降低有关。白色念珠菌 IgG 水平。肠道真菌可能作为改善 ALD 患者预后的治疗靶点。
Alcohol-associated liver disease (ALD) is an important cause of morbidity and mortality worldwide. The intestinal microbiota is involved in the development and progression of ALD; however, little is known about commensal fungi therein. We studied the dynamic changes of the intestinal fungal microbiome, or mycobiome, in 66 patients with alcohol use disorder (AUD) and after 2 weeks of alcohol abstinence using internal transcribed spacer 2 (ITS2) amplicon sequencing of fecal samples. Patients with AUD had significantly increased abundance of the genera Candida, Debaryomyces, Pichia, Kluyveromyces, and Issatchenkia, and of the species Candida albicans and Candida zeylanoides compared with control subjects. Significantly improved liver health markers caspase-cleaved and intact cytokeratin 18 (CK18-M65) levels and controlled attenuation parameter (CAP) in AUD patients after 2 weeks of alcohol abstinence were associated with significantly lower abundance of the genera Candida, Malassezia, Pichia, Kluyveromyces, Issatchenkia, and the species C. albicans and C. zeylanoides. This was mirrored by significantly higher specific anti-C. albicans immunoglobulin G (IgG) and M (IgM) serum levels in AUD patients in relation to control participants, and significantly decreased anti-C. albicans IgG levels in AUD subjects after 2 weeks of abstinence. The intestinal abundance of the genus Malassezia was significantly higher in AUD subjects with progressive liver disease compared with non-progressive liver disease. In conclusion, improved liver health in AUD patients after alcohol abstinence was associated with lower intestinal abundances of Candida and Malassezia, and lower serum anti-C. albicans IgG levels. Intestinal fungi might serve as a therapeutic target to improve the outcome of patients in ALD.
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