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终末期肝硬化中不同的细菌和真菌微生物群簇与抗生素治疗、肠道屏障损伤及全身炎症相关。

Distinct clusters of bacterial and fungal microbiota in end-stage liver cirrhosis correlate with antibiotic treatment, intestinal barrier impairment, and systemic inflammation.

作者信息

Buttler Laura, Velázquez-Ramírez David A, Tiede Anja, Conradi Anna M, Woltemate Sabrina, Geffers Robert, Bremer Birgit, Spielmann Vera, Kahlhöfer Julia, Kraft Anke R M, Schlüter Dirk, Wedemeyer Heiner, Cornberg Markus, Falk Christine, Vital Marius, Maasoumy Benjamin

机构信息

Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.

Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.

出版信息

Gut Microbes. 2025 Dec;17(1):2487209. doi: 10.1080/19490976.2025.2487209. Epub 2025 Apr 21.

Abstract

Decompensated liver cirrhosis (dLC) is associated with intestinal dysbiosis, however, underlying reasons and clinical consequences remain largely unexplored. We investigated bacterial and fungal microbiota, their relation with gut barrier integrity, inflammation, and cirrhosis-specific complications in dLC-patients. Competing-risk analyses were performed to investigate clinical outcomes within 90 days. Samples were prospectively collected from 95 dLC-patients between 2017 and 2022. Quantitative metagenomic analyses clustered patients into three groups (G1-G3) showing distinct microbial patterns. G1 ( = 39) displayed lowest diversity and highest abundance, G2 ( = 24) was dominated by , G3 ( = 29) was most diverse and clustered most closely with healthy controls (HC). Of note, bacterial concentrations were significantly lower in cirrhosis compared with HC, especially for G1 that also showed the lowest capacity to produce short chain fatty acids and secondary bile acids. Consequently, fungal overgrowth, dominated by spp. (51.63%), was observed in G1. Moreover, G1-patients most frequently received antibiotics ( = 33; 86.8%), had highest plasma-levels of Zonulin ( = 0.044) and a proinflammatory cytokine profile along with numerically higher incidences of subsequent infections ( = 0.09). In conclusion, distinct bacterial clusters were observed at qualitative and quantitative levels and correlated with fungal abundances. Antibiotic treatment significantly contributed to dysbiosis, which translated into intestinal barrier impairment and systemic inflammation.

摘要

失代偿期肝硬化(dLC)与肠道菌群失调有关,然而,其潜在原因和临床后果在很大程度上仍未得到充分探索。我们调查了dLC患者的细菌和真菌微生物群,以及它们与肠道屏障完整性、炎症和肝硬化特异性并发症的关系。进行了竞争风险分析以研究90天内的临床结果。在2017年至2022年期间前瞻性收集了95例dLC患者的样本。定量宏基因组分析将患者分为三组(G1 - G3),显示出不同的微生物模式。G1组(n = 39)多样性最低且丰度最高,G2组(n = 24)以……为主,G3组(n = 29)多样性最高且与健康对照(HC)聚类最紧密。值得注意的是,与HC相比,肝硬化患者的细菌浓度显著降低,尤其是G1组,其产生短链脂肪酸和次级胆汁酸的能力也最低。因此,在G1组中观察到以……属(51.63%)为主导的真菌过度生长。此外,G1组患者最常接受抗生素治疗(n = 33;86.8%),血浆中闭合蛋白(Zonulin)水平最高(P = 0.044),具有促炎细胞因子谱,随后感染的发生率在数值上也更高(P = 0.09)。总之,在定性和定量水平上观察到了不同的细菌簇,并且与真菌丰度相关。抗生素治疗显著导致了菌群失调,进而转化为肠道屏障损害和全身炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4679/12054929/01db951f9b33/KGMI_A_2487209_UF0001_OC.jpg

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