Three Klebsiella species as potential pathobionts generating endogenous ethanol in a clinical cohort of patients with auto-brewery syndrome: a case control studyResearch in context
Summary: 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 fa...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396423001251 |
| _version_ | 1797846339344662528 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Guanhua Xue |
| collection | DOAJ |
| description | Summary: 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, but also erased ABS relapse during the follow-up observation of one of the patients. Interpretation: Excessive endogenous alcohol produced by HiAlc Klebsiella species was an underlying cause of bacterial ABS. Combined prescription of appropriate antibiotics, complex probiotic preparation and a controlled diet could be sufficient for treatment of bacteria-caused ABS. Funding: The funders are listed in the acknowledgement. |
| first_indexed | 2024-04-09T17:53:22Z |
| format | Article |
| id | doaj.art-2a0c867af76d44f385b845ef96852925 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-09T17:53:22Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-2a0c867af76d44f385b845ef968529252023-04-15T05:53:15ZengElsevierEBioMedicine2352-39642023-05-0191104560Three Klebsiella species as potential pathobionts generating endogenous ethanol in a clinical cohort of patients with auto-brewery syndrome: a case control studyResearch in contextGuanhua Xue0Junxia Feng1Rui Zhang2Bing Du3Ying Sun4Shiyu Liu5Chao Yan6Xinjuan Liu7Shuheng Du8Yanling Feng9Jinghua Cui10Lin Gan11Hanqing Zhao12Zheng Fan13Xiaohu Cui14Ziying Xu15Tongtong Fu16Chen Li17Lei Huang18Ting Zhang19Jing Wang20Ruifu Yang21Jing Yuan22Department of Bacteriology, Capital Institute of Pediatrics, Beijing, China; Children's Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, China; Children's Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaThe Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaBeijing Chaoyang Hospital, Capital Medical University, Beijing 100020, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaDepartment of Bacteriology, Capital Institute of Pediatrics, Beijing, ChinaBeijing Chaoyang Hospital, Capital Medical University, Beijing 100020, ChinaDepartment of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaChildren's Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, ChinaBeijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China; Corresponding author. Beijing Chaoyang Hospital, Capital Medical University.Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, China; Corresponding author. Beijing Institute of Microbiology and Epidemiology.Department of Bacteriology, Capital Institute of Pediatrics, Beijing, China; Children's Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Corresponding author. Capital Institute of Pediatrics.Summary: 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, but also erased ABS relapse during the follow-up observation of one of the patients. Interpretation: Excessive endogenous alcohol produced by HiAlc Klebsiella species was an underlying cause of bacterial ABS. Combined prescription of appropriate antibiotics, complex probiotic preparation and a controlled diet could be sufficient for treatment of bacteria-caused ABS. Funding: The funders are listed in the acknowledgement.http://www.sciencedirect.com/science/article/pii/S2352396423001251Auto-brewery syndromeGut microbiotaKlebsiellaDiagnosisTreatment |
| spellingShingle | 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 Three Klebsiella species as potential pathobionts generating endogenous ethanol in a clinical cohort of patients with auto-brewery syndrome: a case control studyResearch in context EBioMedicine Auto-brewery syndrome Gut microbiota Klebsiella Diagnosis Treatment |
| title | Three Klebsiella species as potential pathobionts generating endogenous ethanol in a clinical cohort of patients with auto-brewery syndrome: a case control studyResearch in context |
| title_full | Three Klebsiella species as potential pathobionts generating endogenous ethanol in a clinical cohort of patients with auto-brewery syndrome: a case control studyResearch in context |
| title_fullStr | Three Klebsiella species as potential pathobionts generating endogenous ethanol in a clinical cohort of patients with auto-brewery syndrome: a case control studyResearch in context |
| title_full_unstemmed | Three Klebsiella species as potential pathobionts generating endogenous ethanol in a clinical cohort of patients with auto-brewery syndrome: a case control studyResearch in context |
| title_short | Three Klebsiella species as potential pathobionts generating endogenous ethanol in a clinical cohort of patients with auto-brewery syndrome: a case control studyResearch in context |
| title_sort | three klebsiella species as potential pathobionts generating endogenous ethanol in a clinical cohort of patients with auto brewery syndrome a case control studyresearch in context |
| topic | Auto-brewery syndrome Gut microbiota Klebsiella Diagnosis Treatment |
| url | http://www.sciencedirect.com/science/article/pii/S2352396423001251 |
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