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非肥胖非酒精性脂肪性肝病患者肠道菌群特征及熊去氧胆酸对这些特征的影响。

Characteristics of intestinal flora in nonobese nonalcoholic fatty liver disease patients and the impact of ursodeoxycholic acid treatment on these features.

机构信息

Department of Infectious diseases, The Second Hospital of Jiaxing, Jiaxing, Zhejiang, China.

Department of Endocrinology, The Second People's Hospital of Quzhou, Quzhou, Zhejiang, China.

出版信息

Lipids. 2024 Nov;59(6):193-207. doi: 10.1002/lipd.12410. Epub 2024 Sep 9.

DOI:10.1002/lipd.12410
PMID:39246185
Abstract

The study aimed to investigate the alterations in gut microbiota among nonobese individuals with nonalcoholic fatty liver disease (NAFLD) and their response to treatment with ursodeoxycholic acid (UDCA). A total of 90 patients diagnosed with NAFLD and 36 healthy subjects were recruited to participate in this study. Among them, a subgroup of 14 nonobese nonalcoholic steatohepatitis (NASH) were treated with UDCA. Demographic and serologic data were collected for all participants, while stool samples were obtained for fecal microbiome analysis using 16S sequencing. In nonobese NAFLD patients, the alpha diversity of intestinal flora decreased (Shannon index, p < 0.05), and the composition of intestinal flora changed (beta diversity, p < 0.05). The abundance of 20 genera, including Fusobacterium, Lachnoclostridium, Klebsiella, etc., exhibited significant changes (p < 0.05). Among them, nine species including Fusobacterium, Lachnoclostridium, Klebsiella, etc. were found to be associated with abnormal liver enzymes and glucolipid metabolic disorders. Among the 14 NASH patients treated with UDCA, improvements were observed in terms of liver enzymes, CAP values, and E values (p < 0.05), however, no improve the glucolipid metabolism. While the alpha diversity of intestinal flora did not show significant changes after UDCA treatment, there was a notable alteration in the composition of intestinal flora (beta diversity, p < 0.05). Furthermore, UCDA treatment led to an improvement in the relative abundance of Alistipes, Holdemanella, Gilisia, etc. among nonobese NASH patients (p < 0.05). Nonobese NAFLD patients exhibit dysbiosis of the intestinal microbiota. UDCA can ameliorate hepatic enzyme abnormalities and reduce liver fat content in nonobese NASH patients, potentially through its ability to restore intestinal microbiota balance.

摘要

本研究旨在探究非肥胖非酒精性脂肪性肝病(NAFLD)患者肠道微生物群的变化及其对熊去氧胆酸(UDCA)治疗的反应。共招募了 90 名 NAFLD 患者和 36 名健康受试者参与本研究。其中,14 名非肥胖非酒精性脂肪性肝炎(NASH)患者接受 UDCA 治疗。收集所有参与者的人口统计学和血清学数据,并通过 16S 测序获得粪便样本进行粪便微生物组分析。在非肥胖 NAFLD 患者中,肠道菌群的 alpha 多样性降低(Shannon 指数,p<0.05),肠道菌群组成发生变化(beta 多样性,p<0.05)。包括梭菌属、lachnoclostridium 属、克雷伯氏菌属等 20 个属的丰度发生显著变化(p<0.05)。其中,包括梭菌属、lachnoclostridium 属、克雷伯氏菌属等 9 种与异常肝酶和糖脂代谢紊乱有关。在接受 UDCA 治疗的 14 名 NASH 患者中,观察到肝酶、CAP 值和 E 值的改善(p<0.05),但糖脂代谢无改善。UDCA 治疗后肠道菌群的 alpha 多样性无显著变化,但肠道菌群组成发生明显变化(beta 多样性,p<0.05)。此外,UDCA 治疗可改善非肥胖 NASH 患者 Alistipes、Holdemanella、Gilisia 等的相对丰度(p<0.05)。非肥胖 NAFLD 患者肠道微生物群失调。UDCA 可改善非肥胖 NASH 患者肝酶异常和肝脂肪含量,可能通过恢复肠道微生物群平衡。

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