Intestinal Fungal Dysbiosis and Systemic Immune Response to Fungi in Patients With Alcoholic Hepatitis
Intestinal Fungal Dysbiosis and Systemic Immune Response to Fungi in Patients With Alcoholic Hepatitis
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DOI：
10.1002/hep.30832
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发表时间：
2020-02-01
期刊：
影响因子：
13.5
通讯作者：
Schnabl, Bernd
中科院分区：
文献类型：
--
作者：
Lang, Sonja;Duan, Yi;Schnabl, Bernd
长期饮酒会导致肠道通透性增加和肠道微生物群组成发生变化，从而导致酒精相关性肝病的发生和进展。在这种情况下，人们对肠道中的共生真菌知之甚少。我们使用粪便样本的真菌特异性内转录间隔区扩增子测序，研究了一组酒精性肝炎患者、酒精使用障碍患者和非酒精对照患者的肠道菌群。我们进一步测量了血清抗酿酒酵母抗体（ASCA）作为对真菌产品或真菌的全身免疫反应。念珠菌属是两个酒精组的粪便真菌群中最丰富的属，而青霉菌属在非酒精对照的真菌群中占主导地位。与对照组相比，我们观察到酒精组的多样性较低。抗生素或类固醇治疗与多样性降低无关。与酒精使用障碍患者和非酒精对照患者相比，酒精性肝炎患者的 ASCA 水平显着升高。在酒精性肝炎队列中，与 ASCA 水平低于 34 IU/mL 的患者 (80%) 相比，水平至少为 34 IU/mL 的患者的 90 天生存率 (59%) 显着较低，调整后的风险比为 3.13 (95% CI，1.11-8.82；P = 0.031)。结论：与对照组相比，酒精相关性肝病患者的真菌多样性较低，念珠菌过度生长。较高的血清 ASCA 与酒精性肝炎患者死亡率增加相关。肠道真菌可能作为提高生存率的治疗靶点，ASCA 可能有助于预测酒精性肝炎患者的预后。长期饮酒会导致肠道通透性增加和肠道微生物群组成发生变化，从而导致酒精相关性肝病的发生和进展。在这种情况下，人们对肠道中的共生真菌知之甚少。我们使用粪便样本的真菌特异性内转录间隔区扩增子测序，研究了一组酒精性肝炎患者、酒精使用障碍患者和非酒精对照患者的肠道菌群。我们进一步测量了血清抗酿酒酵母抗体（ASCA）作为对真菌产品或真菌的全身免疫反应。念珠菌属是两个酒精组的粪便真菌群中最丰富的属，而青霉菌属在非酒精对照的真菌群中占主导地位。与对照组相比，我们观察到酒精组的多样性较低。抗生素或类固醇治疗与多样性降低无关。与酒精使用障碍患者和非酒精对照患者相比，酒精性肝炎患者的 ASCA 水平显着升高。在酒精性肝炎队列中，与 ASCA 水平低于 34 IU/mL 的患者 (80%) 相比，水平至少为 34 IU/mL 的患者的 90 天生存率 (59%) 显着较低，调整后的风险比为 3.13 (95% CI，1.11-8.82；P = 0.031)。结论：与对照组相比，酒精相关性肝病患者的真菌多样性较低，念珠菌过度生长。较高的血清 ASCA 与酒精性肝炎患者死亡率增加相关。肠道真菌可能作为提高生存率的治疗靶点，ASCA 可能有助于预测酒精性肝炎患者的预后。
Chronic alcohol consumption causes increased intestinal permeability and changes in the intestinal microbiota composition, which contribute to the development and progression of alcohol-related liver disease. In this setting, little is known about commensal fungi in the gut. We studied the intestinal mycobiota in a cohort of patients with alcoholic hepatitis, patients with alcohol use disorder, and nonalcoholic controls using fungal-specific internal transcribed spacer amplicon sequencing of fecal samples. We further measured serum anti-Saccharomyces cerevisiae antibodies (ASCA) as a systemic immune response to fungal products or fungi. Candida was the most abundant genus in the fecal mycobiota of the two alcohol groups, whereas genus Penicillium dominated the mycobiome of nonalcoholic controls. We observed a lower diversity in the alcohol groups compared with controls. Antibiotic or steroid treatment was not associated with a lower diversity. Patients with alcoholic hepatitis had significantly higher ASCA levels compared to patients with alcohol use disorder and to nonalcoholic controls. Within the alcoholic hepatitis cohort, patients with levels of at least 34 IU/mL had a significantly lower 90-day survival (59%) compared with those with ASCA levels less than 34 IU/mL (80%) with an adjusted hazard ratio of 3.13 (95% CI, 1.11-8.82; P = 0.031). Conclusion: Patients with alcohol-associated liver disease have a lower fungal diversity with an overgrowth of Candida compared with controls. Higher serum ASCA was associated with increased mortality in patients with alcoholic hepatitis. Intestinal fungi may serve as a therapeutic target to improve survival, and ASCA may be useful to predict the outcome in patients with alcoholic hepatitis.Chronic alcohol consumption causes increased intestinal permeability and changes in the intestinal microbiota composition, which contribute to the development and progression of alcohol-related liver disease. In this setting, little is known about commensal fungi in the gut. We studied the intestinal mycobiota in a cohort of patients with alcoholic hepatitis, patients with alcohol use disorder, and nonalcoholic controls using fungal-specific internal transcribed spacer amplicon sequencing of fecal samples. We further measured serum anti-Saccharomyces cerevisiae antibodies (ASCA) as a systemic immune response to fungal products or fungi. Candida was the most abundant genus in the fecal mycobiota of the two alcohol groups, whereas genus Penicillium dominated the mycobiome of nonalcoholic controls. We observed a lower diversity in the alcohol groups compared with controls. Antibiotic or steroid treatment was not associated with a lower diversity. Patients with alcoholic hepatitis had significantly higher ASCA levels compared to patients with alcohol use disorder and to nonalcoholic controls. Within the alcoholic hepatitis cohort, patients with levels of at least 34 IU/mL had a significantly lower 90-day survival (59%) compared with those with ASCA levels less than 34 IU/mL (80%) with an adjusted hazard ratio of 3.13 (95% CI, 1.11-8.82; P = 0.031). Conclusion: Patients with alcohol-associated liver disease have a lower fungal diversity with an overgrowth of Candida compared with controls. Higher serum ASCA was associated with increased mortality in patients with alcoholic hepatitis. Intestinal fungi may serve as a therapeutic target to improve survival, and ASCA may be useful to predict the outcome in patients with alcoholic hepatitis.