Objective Cirrhotics have a high rate of infections, which are increasingly fungal or culture-negative in nature. While infected cirrhotics have bacterial dysbiosis, the role of fungi is unclear. We aimed to evaluate gut bacterial and fungal dysbiosis in cross-sectional and longitudinal analyses of outpatient and inpatient cirrhotics and prediction of hospitalisations. Methods Cross-sectional: Age-matched controls, outpatients (with/without antibiotics) and hospitalised uninfected, culture-negative and culture-positive cirrhotics were included and followed for 90 days. Longitudinal: Three studies were conducted: (1) cirrhotics followed over 6 months, (2) outpatient cirrhotics administered antibiotics per standard of care for 5 days and (3) cirrhotics and controls administered omeprazole over 14 days. In all studies, stool bacterial/fungal profiles were analysed. Results Cross-sectional: In 143 cirrhotics and 26 controls, bacterial and fungal diversities were significantly linked. Outpatients on antibiotics and patients with culture-positive infections had the lowest diversities. Bacterial and fungal correlations were complex in uninfected, outpatient and control groups but were markedly skewed in infected patients. 21% were admitted on 90-day follow-up. A lower Bacteroidetes/Ascomycota ratio was associated with lower hospitalisations. Longitudinal: Fungal and bacterial profiles were stable on follow-up (5 days and 6 months). After antibiotics, a significantly reduced bacterial and fungal diversity, higher Candida and lower autochthonous bacterial relative abundance were seen. After omeprazole, changes in bacterial diversity and composition were seen but fungal metrics remained stable. Conclusion There is a significant fungal dysbiosis in cirrhosis, which changes differentially with antibiotics and proton pump inhibitor use, but is otherwise stable over time. A combined bacterial–fungal dysbiosis metric, Bacteroidetes/Ascomycota ratio, can independently predict 90-day hospitalisations in patients with cirrhosis. Clinical trial number NCT01458990.

中文翻译：

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肝硬化中的真菌失调

目的 肝硬化具有很高的感染率，其真菌感染或培养阴性越来越多。虽然感染的肝硬化有细菌失调，但真菌的作用尚不清楚。我们的目的是在门诊和住院肝硬化患者的横断面和纵向分析以及住院预测中评估肠道细菌和真菌的生态失调。方法横断面：包括年龄匹配的对照、门诊患者（有/无抗生素）和住院未感染、培养阴性和培养阳性的肝硬化患者，并随访 90 天。纵向：进行了三项研究：（1）肝硬化患者随访超过 6 个月，（2）门诊肝硬化患者按照标准护理给予抗生素 5 天，（3）肝硬化患者和对照组患者给予奥美拉唑超过 14 天。在所有研究中，分析了粪便细菌/真菌特征。结果横断面：在 143 名肝硬化患者和 26 名对照组中，细菌和真菌的多样性显着相关。抗生素门诊患者和培养阳性感染患者的多样性最低。在未感染组、门诊组和对照组中，细菌和真菌的相关性很复杂，但在感染患者中明显偏斜。21% 的患者在 90 天随访时入院。较低的拟杆菌/子囊菌比率与较低的住院率相关。纵向：真菌和细菌特征在随访中（5 天和 6 个月）稳定。使用抗生素后，细菌和真菌多样性显着降低，念珠菌增多，本土细菌相对丰度降低。服用奥美拉唑后，观察到细菌多样性和组成的变化，但真菌指标保持稳定。结论 肝硬化中存在显着的真菌失调，这种失调随抗生素和质子泵抑制剂的使用而不同，但随着时间的推移保持稳定。一个组合的细菌-真菌生态失调指标，拟杆菌/子囊菌比率，可以独立预测肝硬化患者的 90 天住院率。临床试验编号 NCT01458990。