Metabolomic Signatures of Autoimmune Hepatitis in the Development of Cirrhosis

Li, Shanshan; Niu, Ming; Jing, Jing; Huang, Ying; Zhang, Zi-Teng; Chen, Shuai-shuai; Shi, Ge-zi; He, Xian; Zhang, Haizhu; Xiao, Xiaohe; Zou, Zhengsheng; Yu, Yuecheng; Wang, Jiabo

doi:10.3389/fmed.2021.644376

Cited by 10 publications

(11 citation statements)

References 36 publications

(35 reference statements)

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“…Our results demonstrated that trans- 2-enoyl-OPC4-CoA was downregulated during ascites production and progress. Interestingly, trans- 2-enoyl-OPC4-CoA was also found to be significantly reduced in autoimmune hepatitis-related cirrhosis (AIH) as shown in our previous study ( 15 ). The similar liver response triggered by AIH compared with alcohol consumption suggests that trans- 2-enoyl-OPC4-CoA downregulation might be a common characteristic of cirrhosis progress.…”

Section: Discussionsupporting

confidence: 76%

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Metabolomic Analysis Uncovers Lipid and Amino Acid Metabolism Disturbance During the Development of Ascites in Alcoholic Liver Disease

Cheng

Zhou

et al. 2022

Front. Med.

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Ascites is one of the most common complications of cirrhosis, and there is a dearth of knowledge about ascites-related pathologic metabolism. In this study, 122 alcoholic liver disease (ALD) patients, including 49 cases without ascites, 18 cases with mild-ascites, and 55 cases with large-ascites (1) were established according to the International Ascites Club (2), and untargeted metabolomics coupled with pattern recognition approaches were performed to profile and extract metabolite signatures. A total of 553 metabolites were uniquely discovered in patients with ascites, of which 136 metabolites had been annotated in the human metabolome database. Principal component analysis (PCA) analysis was used to further identify 21 ascites-related fingerprints. The eigenmetabolite calculated by reducing the dimensions of the 21 metabolites could be used to effectively identify those ALD patients with or without ascites. The eigenmetabolite showed a decreasing trend during ascites production and accumulation and was negatively related to the disease progress. These metabolic fingerprints mainly belong to the metabolites in lipid metabolism and the amino acid pathway. The results imply that lipid and amino acid metabolism disturbance may play a critical role in the development of ascites in ALD patients and could be a potent prognosis marker.

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Section: Discussionsupporting

confidence: 76%

“…Data processing and statistical analysis were carried out based on those by Huang et al ( 13 – 15 ). Briefly, metabolomic data were normalized by the inclusion of multiple internal standards and pool calibration–response correction in MetaboAnalyst version 4.0 after being processed in MassHunter Profinder 1 .…”

Section: Methodsmentioning

confidence: 99%

Metabolomic Analysis Uncovers Lipid and Amino Acid Metabolism Disturbance During the Development of Ascites in Alcoholic Liver Disease

Cheng

Zhou

et al. 2022

Front. Med.

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“…The immune system competes with other programs in the body for energy. In addition, the energy supply is significantly disordered in the body, which is mainly manifested in the large consumption of nutrients (such as carbohydrate, proteins and lipids) and the enhancement of degradation in carbohydrate, lipid and protein ( Freitas et al., 2018 ; Li et al., 2021 ). In our study, the gene function which was significant enriched in AIH were mainly associated with energy metabolism.…”

Section: Discussionmentioning

confidence: 99%

Oral Microbiome Characteristics in Patients With Autoimmune Hepatitis

Rao

Lou²,

Lü

et al. 2021

Front. Cell. Infect. Microbiol.

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Autoimmune hepatitis (AIH) is a common cause of liver cirrhosis. To identify the characteristics of the oral microbiome in patients with AIH, we collected 204 saliva samples including 68 AIH patients and 136 healthy controls and performed microbial MiSeq sequencing after screening. All samples were randomly divided into discovery cohorts (46 AIH and 92 HCs) and validation cohorts (22 AIH and 44 HCs). Moreover, we collected samples of 12 AIH patients from Hangzhou for cross-regional validation. We described the oral microbiome characteristics of AIH patients and established a diagnostic model. In the AIH group, the oral microbiome diversity was significantly increased. The microbial communities remarkably differed between the two groups. Seven genera, mainly Fusobacterium, Actinomyces and Capnocytophaga, were dominant in the HC group, while 51 genera, Streptococcus, Veillonella and Leptotrichia, were enriched in the AIH group. Notably, we found 23 gene functions, including Membrane Transport, Carbohydrate Metabolism, and Glycerolipid metabolism that were dominant in AIH and 31 gene functions that prevailed in HCs. We further investigated the correlation between the oral microbiome and clinical parameters. The optimal 5 microbial markers were figured out through a random forest model, and the distinguishing potential achieved 99.88% between 46 AIH and 92 HCs in the discovery cohort and 100% in the validation cohort. Importantly, the distinguishing potential reached 95.55% in the cross-regional validation cohort. In conclusion, this study is the first to characterize the oral microbiome in AIH patients and to report the successful establishment of a diagnostic model and the cross-regional validation of microbial markers for AIH. Importantly, oral microbiota-targeted biomarkers may be able to serve as powerful and noninvasive diagnostic tools for AIH.

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“…It improves mitochondrial functions and exerts beneficial effects in neurological disorders ( 49 ). An upregulated lysoPA correlated with the occurrence of several inflammatory conditions, such as asthma ( 50 ), cancer ( 51 ), and autoimmune hepatitis ( 52 ). We identified phosphatidylserine (PS), phosphatidylethanolamine (PE), and lysoPA as differential serum metabolites in NMDAR encephalitis patients versus controls.…”

Section: Discussionmentioning

confidence: 99%

Disturbance of Gut Bacteria and Metabolites Are Associated with Disease Severity and Predict Outcome of NMDAR Encephalitis: A Prospective Case–Control Study

Gong

Liu

et al. 2022

Front. Immunol.

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ObjectiveWe aimed to investigate the associations between the intestinal microbiota, metabolites, cytokines, and clinical severity in anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and to further determine the predictive value of the intestinal microbiota or metabolites in clinical prognosis.MethodsIn this prospective observational cohort study of 58 NMDAR encephalitis patients and 49 healthy controls, fecal microbiota, metabolites, and cytokines were quantified and characterized by16S rRNA gene sequencing, liquid chromatography–mass spectrometry, and the Luminex assay, respectively.ResultsThere were marked variations in the gut microbiota composition and metabolites in critically ill patients. We identified 8 metabolite modules (mainly characterized by fatty acid, glycerophosphoethanolamines, and glycerophosphocholines) that were distinctly classified as negatively or positively associated with bacterial co-abundance groups (CAGs). These CAGs were mainly composed of Bacteroides, Eubacterium_hallii_group, Anaerostipes, Ruminococcus, Butyricicoccus, and Faecalibacterium, which were substantially altered in patients. In addition, these fecal and serum metabolic modules were further correlated with the serum cytokines. Additionally, the combination of clinical features, microbial marker (Granulicatella), and a panel of metabolic markers could further enhance the performance of prognosis discrimination significantly, which yielded an area under the receiver operating characteristic curve of (AUC) of 0.94 (95%CI = 0.7–0.9). Patients with low bacterial diversity are more likely to develop relapse than those with higher bacterial diversity (log-rank p = 0.04, HR = 2.7, 95%CI = 1.0–7.0).InterpretationThe associations between the multi-omics data suggested that certain bacteria might affect the pathogenesis of NMDAR encephalitis by modulating the metabolic pathways of the host and affecting the production of pro-inflammatory cytokines. Furthermore, the disturbance of fecal bacteria may predict the long-term outcome and relapse in NMDAR encephalitis.

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Metabolomic Signatures of Autoimmune Hepatitis in the Development of Cirrhosis

Cited by 10 publications

References 36 publications

Metabolomic Analysis Uncovers Lipid and Amino Acid Metabolism Disturbance During the Development of Ascites in Alcoholic Liver Disease

Metabolomic Analysis Uncovers Lipid and Amino Acid Metabolism Disturbance During the Development of Ascites in Alcoholic Liver Disease

Oral Microbiome Characteristics in Patients With Autoimmune Hepatitis

Disturbance of Gut Bacteria and Metabolites Are Associated with Disease Severity and Predict Outcome of NMDAR Encephalitis: A Prospective Case–Control Study

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