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1
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Tan EY, Muthiah MD, Sanyal AJ. Metabolomics at the cutting edge of risk prediction of MASLD. Cell Rep Med 2024; 5:101853. [PMID: 39657668 PMCID: PMC11722125 DOI: 10.1016/j.xcrm.2024.101853] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 10/12/2024] [Accepted: 11/14/2024] [Indexed: 12/12/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health threat globally. Management of patients afflicted with MASLD and research in this domain are limited by the lack of robust well-established non-invasive biomarkers for diagnosis, prognostication, and monitoring. The circulating metabolome reflects both the systemic metabo-inflammatory milieu and changes in the liver in affected individuals. In this review we summarize the available literature on changes in the different components of the metabolome in MASLD with a focus on changes that are linked to the presence of underlying steatohepatitis, severity of disease activity, and fibrosis stage. We further summarize the existing literature around biomarker panels that are derived from interrogation of the metabolome. Their relevance to disease biology and utility in practice are also discussed. We further highlight potential direction for future studies particularly to ensure they are fit for purpose and suitable for widespread use.
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Affiliation(s)
- En Ying Tan
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore.
| | - Mark D Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Arun J Sanyal
- Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
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2
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Beyoğlu D, Popov YV, Idle JR. Metabolomic Hallmarks of Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease. Int J Mol Sci 2024; 25:12809. [PMID: 39684520 DOI: 10.3390/ijms252312809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 11/15/2024] [Accepted: 11/19/2024] [Indexed: 12/18/2024] Open
Abstract
From a detailed review of 90 experimental and clinical metabolomic investigations of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD), we have developed metabolomic hallmarks for both obesity and MASLD. Obesity studies were conducted in mice, rats, and humans, with consensus biomarker groups in plasma/serum being essential and nonessential amino acids, energy metabolites, gut microbiota metabolites, acylcarnitines and lysophosphatidylcholines (LPC), which formed the basis of the six metabolomic hallmarks of obesity. Additionally, mice and rats shared elevated cholesterol, humans and rats shared elevated fatty acids, and humans and mice shared elevated VLDL/LDL, bile acids and phosphatidylcholines (PC). MASLD metabolomic studies had been performed in mice, rats, hamsters, cows, geese, blunt snout breams, zebrafish, and humans, with the biomarker groups in agreement between experimental and clinical investigations being energy metabolites, essential and nonessential amino acids, fatty acids, and bile acids, which lay the foundation of the five metabolomic hallmarks of MASLD. Furthermore, the experimental group had higher LPC/PC and cholesteryl esters, and the clinical group had elevated acylcarnitines, lysophosphatidylethanolamines/phosphatidylethanolamines (LPE/PE), triglycerides/diglycerides, and gut microbiota metabolites. These metabolomic hallmarks aid in the understanding of the metabolic role played by obesity in MASLD development, inform mechanistic studies into underlying disease pathogenesis, and are critical for new metabolite-inspired therapies.
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Affiliation(s)
- Diren Beyoğlu
- Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences, Western New England University, Springfield, MA 01119, USA
| | - Yury V Popov
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Jeffrey R Idle
- Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences, Western New England University, Springfield, MA 01119, USA
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Dai S, Guo X, Liu S, Tu L, Hu X, Cui J, Ruan Q, Tan X, Lu H, Jiang T, Xu J. Application of intelligent tongue image analysis in Conjunction with microbiomes in the diagnosis of MAFLD. Heliyon 2024; 10:e29269. [PMID: 38617943 PMCID: PMC11015139 DOI: 10.1016/j.heliyon.2024.e29269] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 03/22/2024] [Accepted: 04/03/2024] [Indexed: 04/16/2024] Open
Abstract
Background Metabolic associated fatty liver disease (MAFLD) is a widespread liver disease that can lead to liver fibrosis and cirrhosis. Therefore, it is essential to develop early diagnosic and screening methods. Methods We performed a cross-sectional observational study. In this study, based on data from 92 patients with MAFLD and 74 healthy individuals, we observed the characteristics of tongue images, tongue coating and intestinal flora. A generative adversarial network was used to extract tongue image features, and 16S rRNA sequencing was performed using the tongue coating and intestinal flora. We then applied tongue image analysis technology combined with microbiome technology to obtain an MAFLD early screening model with higher accuracy. In addition, we compared different modelling methods, including Extreme Gradient Boosting (XGBoost), random forest, neural networks(MLP), stochastic gradient descent(SGD), and support vector machine(SVM). Results The results show that tongue-coating Streptococcus and Rothia, intestinal Blautia, and Streptococcus are potential biomarkers for MAFLD. The diagnostic model jointly incorporating tongue image features, basic information (gender, age, BMI), and tongue coating marker flora (Streptococcus, Rothia), can have an accuracy of 96.39%, higher than the accuracy value except for bacteria. Conclusion Combining computer-intelligent tongue diagnosis with microbiome technology enhances MAFLD diagnostic accuracy and provides a convenient early screening reference.
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Affiliation(s)
- Shixuan Dai
- Department of College of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Road, Shanghai, 201203, China
| | - Xiaojing Guo
- Department of Anesthesiology, Naval Medical University, No. 800, Xiangyin Road, Shanghai,200433, China
| | - Shi Liu
- Department of College of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Road, Shanghai, 201203, China
| | - Liping Tu
- Department of College of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Road, Shanghai, 201203, China
| | - Xiaojuan Hu
- Department of College of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Road, Shanghai, 201203, China
| | - Ji Cui
- Department of College of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Road, Shanghai, 201203, China
| | - QunSheng Ruan
- Department of Software, Xiamen University, No. 422, Siming South Road, Siming District, Xiamen City, Fujian Province, 361005, China
| | - Xin Tan
- Department of Computer Science and Technology, East China Normal University, No. 3663, Zhongshan North Road, Shanghai, 200062, China
| | - Hao Lu
- Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No. 528, Zhangheng Road, Shanghai,200021, China
| | - Tao Jiang
- Department of College of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Road, Shanghai, 201203, China
| | - Jiatuo Xu
- Department of College of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Road, Shanghai, 201203, China
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4
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Vitulo M, Gnodi E, Rosini G, Meneveri R, Giovannoni R, Barisani D. Current Therapeutical Approaches Targeting Lipid Metabolism in NAFLD. Int J Mol Sci 2023; 24:12748. [PMID: 37628929 PMCID: PMC10454602 DOI: 10.3390/ijms241612748] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 08/07/2023] [Accepted: 08/10/2023] [Indexed: 08/27/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD, including nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH)) is a high-prevalence disorder, affecting about 1 billion people, which can evolve to more severe conditions like cirrhosis or hepatocellular carcinoma. NAFLD is often concomitant with conditions of the metabolic syndrome, such as central obesity and insulin-resistance, but a specific drug able to revert NAFL and prevent its evolution towards NASH is still lacking. With the liver being a key organ in metabolic processes, the potential therapeutic strategies are many, and range from directly targeting the lipid metabolism to the prevention of tissue inflammation. However, side effects have been reported for the drugs tested up to now. In this review, different approaches to the treatment of NAFLD are presented, including newer therapies and ongoing clinical trials. Particular focus is placed on the reverse cholesterol transport system and on the agonists for nuclear factors like PPAR and FXR, but also drugs initially developed for other conditions such as incretins and thyromimetics along with validated natural compounds that have anti-inflammatory potential. This work provides an overview of the different therapeutic strategies currently being tested for NAFLD, other than, or along with, the recommendation of weight loss.
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Affiliation(s)
- Manuela Vitulo
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy; (M.V.); (E.G.); (R.M.)
| | - Elisa Gnodi
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy; (M.V.); (E.G.); (R.M.)
| | - Giulia Rosini
- Department of Biology, University of Pisa, 56021 Pisa, Italy; (G.R.); (R.G.)
| | - Raffaella Meneveri
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy; (M.V.); (E.G.); (R.M.)
| | - Roberto Giovannoni
- Department of Biology, University of Pisa, 56021 Pisa, Italy; (G.R.); (R.G.)
| | - Donatella Barisani
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy; (M.V.); (E.G.); (R.M.)
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Amer B, Deshpande RR, Bird SS. Simultaneous Quantitation and Discovery (SQUAD) Analysis: Combining the Best of Targeted and Untargeted Mass Spectrometry-Based Metabolomics. Metabolites 2023; 13:metabo13050648. [PMID: 37233689 DOI: 10.3390/metabo13050648] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 04/27/2023] [Accepted: 05/05/2023] [Indexed: 05/27/2023] Open
Abstract
Untargeted and targeted approaches are the traditional metabolomics workflows acquired for a wider understanding of the metabolome under focus. Both approaches have their strengths and weaknesses. The untargeted, for example, is maximizing the detection and accurate identification of thousands of metabolites, while the targeted is maximizing the linear dynamic range and quantification sensitivity. These workflows, however, are acquired separately, so researchers compromise either a low-accuracy overview of total molecular changes (i.e., untargeted analysis) or a detailed yet blinkered snapshot of a selected group of metabolites (i.e., targeted analysis) by selecting one of the workflows over the other. In this review, we present a novel single injection simultaneous quantitation and discovery (SQUAD) metabolomics that combines targeted and untargeted workflows. It is used to identify and accurately quantify a targeted set of metabolites. It also allows data retro-mining to look for global metabolic changes that were not part of the original focus. This offers a way to strike the balance between targeted and untargeted approaches in one single experiment and address the two approaches' limitations. This simultaneous acquisition of hypothesis-led and discovery-led datasets allows scientists to gain more knowledge about biological systems in a single experiment.
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Affiliation(s)
- Bashar Amer
- Thermo Fisher Scientific, San Jose, 95134 CA, USA
| | | | - Susan S Bird
- Thermo Fisher Scientific, San Jose, 95134 CA, USA
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6
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Serum metabolomics-based heterogeneities and screening strategy for metabolic dysfunction-associated fatty liver disease (MAFLD). Clin Chim Acta 2023; 538:203-210. [PMID: 36549641 DOI: 10.1016/j.cca.2022.12.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 11/27/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIMS Metabolic dysfunction-associated fatty liver disease (MAFLD) brings heavy clinical and economic burdens to society, while understandings on heterogeneities are limited. MATERIALS AND METHODS We conducted a serum metabolomics study to reveal the metabolic heterogeneities and develop a diagnostic strategy for MAFLD using a discovery set consisting of 122 biopsy-proven MAFLD patients [lean (n = 12), overweight (n = 20), obese (n = 74), type 2 diabetes mellitus (T2DM, n = 16)] and 35 controls, and a validation set containing 60 biopsy-proven MAFLD patients (20 lean, 20 obese and 20 T2DM) and 20 controls. RESULTS Mitochondrial dysfunction, destructed phospholipids homeostasis, and folate deficiency were most severe in MAFLD concurrent T2DM patients. Formiminoglutamate, sphinganine and sphingosine correlated positively with HbA1c, while glycoursodeoxycholicacidsulfate correlated positively with AST. Additionally, the linear discriminant analysis (LDA) model using metabolites 5-hydroxyhexanoate, ribitol and formiminoglutamate demonstrated pretty good performance in screening for MAFLD patients, with AUC for validation samples being 0.94 (CI: 0.88-1.0). For easier clinical applications, an M-index based on the three metabolites was further designed. CONCLUSION Our study supports that MAFLD concurrent T2DM patients deserve particular attentions in clinical follow-up, and paves the way for developing more effective diagnostic options in future studies.
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Rosso AD, Aguilera P, Quesada S, Mascardi F, Mascuka SN, Cimolai MC, Cerezo J, Spiazzi R, Conlon C, Milano C, Iraola GM, Penas-Steinhardt A, Belforte FS. Comprehensive Phenotyping in Inflammatory Bowel Disease: Search for Biomarker Algorithms in the Transkingdom Interactions Context. Microorganisms 2022; 10:2190. [PMID: 36363782 PMCID: PMC9698371 DOI: 10.3390/microorganisms10112190] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 10/27/2022] [Accepted: 11/01/2022] [Indexed: 11/06/2022] Open
Abstract
Inflammatory bowel disease (IBD) is the most common form of intestinal inflammation associated with a dysregulated immune system response to the commensal microbiota in a genetically susceptible host. IBD includes ulcerative colitis (UC) and Crohn's disease (CD), both of which are remarkably heterogeneous in their clinical presentation and response to treatment. This translates into a notable diagnostic challenge, especially in underdeveloped countries where IBD is on the rise and access to diagnosis or treatment is not always accessible for chronic diseases. The present work characterized, for the first time in our region, epigenetic biomarkers and gut microbial profiles associated with UC and CD patients in the Buenos Aires Metropolitan area and revealed differences between non-IBD controls and IBD patients. General metabolic functions associated with the gut microbiota, as well as core microorganisms within groups, were also analyzed. Additionally, the gut microbiota analysis was integrated with relevant clinical, biochemical and epigenetic markers considered in the follow-up of patients with IBD, with the aim of generating more powerful diagnostic tools to discriminate phenotypes. Overall, our study provides new insights into data analysis algorithms to promote comprehensive phenotyping tools using quantitative and qualitative analysis in a transkingdom interactions network context.
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Affiliation(s)
- Ayelén D. Rosso
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires C1425FQB, Argentina
- Instituto de Ecología y Desarrollo Sustentable (INEDES-CONICET-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
| | - Pablo Aguilera
- Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires C1425FQB, Argentina
| | - Sofía Quesada
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires C1425FQB, Argentina
| | - Florencia Mascardi
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires C1425FQB, Argentina
- Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB), CONICET, Instituto Universitario del Hospital Italiano (IUHI), Hospital Italiano de Buenos Aires (HIBA), Ciudad Autónoma de Buenos Aires C1199, Argentina
| | - Sebastian N. Mascuka
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
| | - María C. Cimolai
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
| | - Jimena Cerezo
- Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, Ciudad Autónoma de Buenos Aires 1704, Argentina
| | - Renata Spiazzi
- Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, Ciudad Autónoma de Buenos Aires 1704, Argentina
| | - Carolina Conlon
- Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, Ciudad Autónoma de Buenos Aires 1704, Argentina
| | - Claudia Milano
- Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, Ciudad Autónoma de Buenos Aires 1704, Argentina
| | - Gregorio M. Iraola
- Laboratorio de Genómica Microbiana, Institut Pasteur Montevideo, Montevideo 11400, Uruguay
- Centro de Biología Integrativa, Universidad Mayor, Santiago 7510041, Chile
- Wellcome Sanger Institute, Wellcome Genome Campus, Cambridgeshire CB10 1SA, UK
| | - Alberto Penas-Steinhardt
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires C1425FQB, Argentina
- Instituto Universitario de Ciencias de la Salud, Fundación H.A. Barceló, Ciudad Autónoma de Buenos Aires 1127, Argentina
| | - Fiorella S. Belforte
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires C1425FQB, Argentina
- Instituto de Ecología y Desarrollo Sustentable (INEDES-CONICET-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
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Shao M, Lu Y, Xiang H, Wang J, Ji G, Wu T. Application of metabolomics in the diagnosis of non-alcoholic fatty liver disease and the treatment of traditional Chinese medicine. Front Pharmacol 2022; 13:971561. [PMID: 36091827 PMCID: PMC9453477 DOI: 10.3389/fphar.2022.971561] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 07/25/2022] [Indexed: 12/01/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease around the world, and it often coexists with insulin resistance-related diseases including obesity, diabetes, hyperlipidemia, and hypertension, which seriously threatens human health. Better prevention and treatment strategies are required to improve the impact of NAFLD. Although needle biopsy is an effective tool for diagnosing NAFLD, this method is invasive and difficult to perform. Therefore, it is very important to develop more efficient approaches for the early diagnosis of NAFLD. Traditional Chinese medicine (TCM) can play a certain role in improving symptoms and protecting target organs, and its mechanism of action needs to be further studied. Metabolomics, the study of all metabolites that is thought to be most closely associated with the patients' characters, can provide useful clinically biomarkers that can be applied to NAFLD and may open up new methods for diagnosis. Metabolomics technology is consistent with the overall concept of TCM, and it can also be used as a potential mechanism to explain the effects of TCM by measuring biomarkers by metabolomics. Based on PubMed/MEDLINE and other databases, this paper retrieved relevant literature NAFLD and TCM intervention in NAFLD using metabolomics technology in the past 5 years were searched, and the specific metabolites associated with the development of NAFLD and the potential mechanism of Chinese medicine on improving symptoms were summarized.
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Affiliation(s)
- Mingmei Shao
- Baoshan District Hospital of Intergrated Traditional Chinese and Western Medicine, Shanghai, China
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yifei Lu
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hongjiao Xiang
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Junmin Wang
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Guang Ji
- Baoshan District Hospital of Intergrated Traditional Chinese and Western Medicine, Shanghai, China
- Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Tao Wu
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Mei M, Liu D, Tang X, You Y, Peng B, He X, Huang J. Vitamin B6 Metabolic Pathway is Involved in the Pathogenesis of Liver Diseases via Multi-Omics Analysis. J Hepatocell Carcinoma 2022; 9:729-750. [PMID: 35979344 PMCID: PMC9377404 DOI: 10.2147/jhc.s370255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 08/04/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose To clarify the underlying regulatory mechanisms of progression from liver cirrhosis to hepatocellular carcinoma (HCC), we analyzed the microbiomics, metabolomics, and proteomics in plasma and tissues from patients with HCC or decompensated liver cirrhosis (DC). Patients and Methods Tissues and plasma from 44 HCC patients and 28 patients with DC were collected for metabolomic analysis. 16S rRNA sequencing was performed in nine HCC tissues (HCCT), four distal noncancerous tissues (HCCN), and 11 DC tissues (DCT). Five HCC tissues had liver cirrhosis (HCCT-LC). Five hepatocellular carcinoma tissues without liver cirrhosis (HCCT-NLC) and five DCT were selected for proteomic sequencing. After combining proteomic and metabolomic analysis, we constructed a mouse model of chronic liver injury using carbon tetrachloride (CCl4) and treated them with vitamin B6 (VB6). Results 16s rRNA sequence results showed that HCC tissues had higher alpha diversity. The highest LDA scores were detected for Elizabethkingia in HCCT, Subsaxibacter in DCT, and Stenotrophomon in HCCN. Metabolomics results demonstrated some metabolites, including capric acid, L-threonate, choline, alpha-D-Glucose, D-ribose, betaine, 2E-eicosenoic acid, linoleic acid, L-palmitoylcarnitine, taurodeoxycholic acid, L-pyroglutamic acid, androsterone sulfate, and phthalic acid mono-2-ethylhexyl ester (MEHP), had better diagnostic efficacy than AFP (AUC: 0.852; 95% CI: 0.749, 0.954). In a combined analysis of metabolomics and proteomics, we found that HCCT-LC had more obvious disorders of VB6 metabolism and pentose and glucuronate interconversions than DCT, and kynurenine metabolism disorder was more significant in HCCT-LC than in HCCT-NLC. In the CCl4-induced chronic liver injury model, after VB6 supplementation, inflammatory cell infiltration, hepatocyte edema, and degeneration were significantly improved. Conclusion We found significant differences in the flora distribution between HCCT and DC; MEHP was a new diagnostic biomarker of HCC, and VB6 ameliorated the inflammatory cell infiltration, hepatocyte edema, and degeneration in chronic liver injury.
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Affiliation(s)
- Meihua Mei
- Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation & Transplant Immunology, Guangzhou, 510080, People's Republic of China.,Guangdong Provincial International Cooperation Base of Science & Technology (Organ Transplantation), Guangzhou, 510080, People's Republic of China.,Department of Laboratory Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China
| | - Danping Liu
- Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation & Transplant Immunology, Guangzhou, 510080, People's Republic of China.,Guangdong Provincial International Cooperation Base of Science & Technology (Organ Transplantation), Guangzhou, 510080, People's Republic of China.,Department of Laboratory Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China
| | - Xiuxin Tang
- Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation & Transplant Immunology, Guangzhou, 510080, People's Republic of China.,Guangdong Provincial International Cooperation Base of Science & Technology (Organ Transplantation), Guangzhou, 510080, People's Republic of China.,Department of Laboratory Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China
| | - Ying You
- Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation & Transplant Immunology, Guangzhou, 510080, People's Republic of China.,Guangdong Provincial International Cooperation Base of Science & Technology (Organ Transplantation), Guangzhou, 510080, People's Republic of China.,Department of Laboratory Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China
| | - Baogang Peng
- Hepatobiliary Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China
| | - Xiaoshun He
- Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation & Transplant Immunology, Guangzhou, 510080, People's Republic of China.,Guangdong Provincial International Cooperation Base of Science & Technology (Organ Transplantation), Guangzhou, 510080, People's Republic of China
| | - Junqi Huang
- Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation & Transplant Immunology, Guangzhou, 510080, People's Republic of China.,Guangdong Provincial International Cooperation Base of Science & Technology (Organ Transplantation), Guangzhou, 510080, People's Republic of China.,Department of Laboratory Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China
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Lanzaro F, Guarino S, D'Addio E, Salvatori A, D'Anna JA, Marzuillo P, Miraglia Del Giudice E, Di Sessa A. Metabolic-associated fatty liver disease from childhood to adulthood: State of art and future directions. World J Hepatol 2022; 14:1087-1098. [PMID: 35978659 PMCID: PMC9258256 DOI: 10.4254/wjh.v14.i6.1087] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 12/26/2021] [Accepted: 04/25/2022] [Indexed: 02/06/2023] Open
Abstract
In 2020, an international group of experts proposed to replace the term of nonalcoholic fatty liver disease with metabolic-associated fatty liver disease (MAFLD). This recent proposal reflects the close association of fatty liver with metabolic derangements, as demonstrated by previous robust data. Several factors [including genetics, inflammation, metabolic abnormalities, insulin resistance (IR), obesity, prenatal determinants, and gut-liver axis] have been found to be involved in MAFLD pathophysiology, but this tangled puzzle remains to be clearly understood. In particular, IR has been recognized as a key player in metabolic impairments development in children with fatty liver. On this ground, MAFLD definition focuses on the pathophysiological basis of the disease, by emphasizing the crucial role of metabolic impairments in this condition. Although primarily developed for adults, MAFLD diagnostic criteria have been recently updated with an age-appropriate definition for sex and age percentiles, because of the increasing attention to cardiometabolic risk in childhood. To date, accumulating evidence is available on the feasibility of MAFLD definition in clinical practice, but some data are still conflicting in highly selected populations. Considering the growing prevalence worldwide of fatty liver and its close relationship with metabolic dysfunction both in children and adults with subsequent increased cardiovascular risk, early strategies for MAFLD identification, treatment and prevention are needed. Novel therapeutic insights for MAFLD based on promising innovative biological techniques are also emerging. We aimed to summarize the most recent evidence in this intriguing research area both in children and adults.
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Affiliation(s)
- Francesca Lanzaro
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Stefano Guarino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Elisabetta D'Addio
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Alessandra Salvatori
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Josè Alberto D'Anna
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy.
| | - Emanuele Miraglia Del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
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Yang Q, Zhang L, Li Q, Gu M, Qu Q, Yang X, Yi Q, Gu K, Kuang L, Hao M, Xu J, Yang H. Characterization of microbiome and metabolite analyses in patients with metabolic associated fatty liver disease and type II diabetes mellitus. BMC Microbiol 2022; 22:105. [PMID: 35421921 PMCID: PMC9011963 DOI: 10.1186/s12866-022-02526-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 04/08/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
State-of-the-art renewal has indicated the improvement of diagnostics of patients with metabolic associated fatty liver disease (MAFLD) and/or type II diabetes mellitus (T2DM) by dissecting the clinical characteristics as well as genomic analysis. However, the deficiency of the characterization of microbial and metabolite signatures largely impedes the symptomatic treatment.
Methods
For the purpose, we retrospectively analyzed the clinical data of 20 patients with MAFLD (short for “M”), 20 cases with MAFLD and T2DM (short for “MD”), together with 19 healthy donors (short for “Ctr”). Microbial and metabolite analyses were further conducted to explore the similarities and differences among the aforementioned populations based on feces and blood samples, respectively.
Results
Compared with those in the Ctr group, patients with M or MD revealed multifaceted similarities (e.g., Age, ALP, LDL, BUN) and distinctions in clinical indicators of liver (e.g., BMI, ALT, PCHE, CAP). With the aid of microbial and metabolite analyses as well as bioinformatic analyses, we found that the characteristics of gut microbiota (e.g., abundance, hierarchical clustering, cladogram, species) and lipid metabolism (e.g., metabolite, correlation coefficient and scatter plot) were distinct among the indicated groups.
Conclusions
The patients with MD revealed multifaceted similarities and distinctions in characteristics of microbiome and metabolites with those in the M and HD groups, and in particular, the significantly expressed microbes (e.g., Elusimicrobiota, Berkelbacteria, Cyanobacteria, Peregrinibacteria) and lipid metabolites (e.g., Lipid-Q-P-0765, Lipid-Q-P-0216, Lipid-Q-P-0034, Lipid-Q-P-0800), which would collectively benefit the clinical diagnosis of MAFLD and T2DM.
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Single Nucleotide Polymorphism of Genes Associated with Metabolic Fatty Liver Disease. JOURNAL OF ONCOLOGY 2022; 2022:9282557. [PMID: 35154322 PMCID: PMC8831055 DOI: 10.1155/2022/9282557] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 01/05/2022] [Accepted: 01/13/2022] [Indexed: 02/08/2023]
Abstract
Aims The present study aimed to reveal the relationship between single nucleotide polymorphism (SNP) of PNPLA3, TM6SF2, MBOAT7, GATAD2A, and STAT3 genes and metabolism-related fatty liver disease (MAFLD), so as to provide a research basis for further exploring the diagnosis and treatment of diseases at the molecular level. Methods A total of 564 patients were included in the physical examination center of Xinjiang Karamay People's Hospital. They were divided into an MAFLD case group and a healthy control group. The whole blood DNA of each sample was extracted by a whole blood genomic DNA extraction kit, and the genotypes of PNPLA3 rs738409, MBOAT7 rs64173, STAT3 rs744166, TM6SF2 rs58542926, and GATAD2A rs4808199 were performed; after adjusting for confounding factors, the additive model, dominant model, and recessive model of each gene were analyzed by multivariate logistic regression. Results The CC genotype of the PNPLA3 gene rs738409 and the TT genotype of the MBOAT7 gene rs64173 are risk factors in the occurrence of MAFLD. The AA genotype of the STAT3 gene rs744166 is a protective factor of MAFLD, while TM6SF2 rs58542926 and GATAD2A rs4808199 show no significant correlation with MAFLD.
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