Three Klebsiella species as potential pathobionts generating endogenous ethanol in a clinical cohort of patients with auto-brewery syndrome: a case control study

作者：Guanhua Xue, Junxia Feng, Rui Zhang, Bing Du, Ying Sun, Shiyu Liu, Chao Yan, Xinjuan Liu, Shuheng Du, Yanling Feng, Jinghua Cui, Lin Gan, Hanqing Zhao, Zheng Fan, Xiaohu Cui, Ziying Xu, Tongtong Fu, Chen Li, Lei Huang, Ting Zhang, Jing Wang, Ruifu Yang, Jing Yuan · 发表于：EBioMedicine · 年份：2023 · DOI：10.1016/j.ebiom.2023.104560 · 被引用次数：55 · 研究领域：Alcohol Consumption and Health Effects、Alcoholism and Thiamine Deficiency、Microbial metabolism and enzyme function

BACKGROUND: Patients with auto-brewery syndrome (ABS) become inebriated after the ingestion of an alcohol-free, high-carbohydrate diet. Our previous work has shown that high-alcohol-producing (HiAlc) Klebsiella pneumoniae can generate excessive endogenous ethanol and cause non-alcoholic fatty liver disease (NAFLD). Therefore, it is reasonable to speculate that such bacteria might play an important role in the pathogenesis of ABS. METHODS: The characteristics and metabolites of the intestinal flora from a clinical cohort of patients with ABS were analysed during different stages of disease and compared to a group of healthy controls. An in vitro culture system of relevant samples was used for screening drug sensitivity and ABS-inducing factors. Rabbit intestinal and murine models were established to verify if the isolated strains could induce ABS in vivo. FINDINGS: We observed intestinal dysbiosis with decreased abundance of Firmicutes and increased of Proteobacteria in patients with ABS compared with healthy controls. The abundance of the genus Klebsiella in Enterobacteriaceae was strongly associated with fluctuations of patient's blood alcohol concentration. We isolated three species of HiAlc Klebsiella from ABS patients, which were able to induce ABS in mice. Monosaccharide content was identified as a potential food-related inducing factor for alcohol production. Treatments with antibiotics, a complex probiotic preparation and a low-carbohydrate diet not only alleviated ABS...