Plasma and stool metabolomics to identify microbiota derived-biomarkers of metabolic dysfunction-associated fatty liver disease: effect of PNPLA3 genotype.
Metabolic dysfunction-associated fatty liver disease
Metabolomics
Microbiota
PNPLA3
Plasma
Stool
Journal
Metabolomics : Official journal of the Metabolomic Society
ISSN: 1573-3890
Titre abrégé: Metabolomics
Pays: United States
ID NLM: 101274889
Informations de publication
Date de publication:
16 06 2021
16 06 2021
Historique:
received:
23
01
2021
accepted:
08
06
2021
entrez:
17
6
2021
pubmed:
18
6
2021
medline:
19
1
2022
Statut:
epublish
Résumé
Non-invasive biomarkers are needed for metabolic dysfunction-associated fatty liver disease (MAFLD), especially for patients at risk of disease progression in high-prevalence areas. The microbiota and its metabolites represent a niche for MAFLD biomarker discovery. However, studies are not reproducible as the microbiota is variable. We aimed to identify microbiota-derived metabolomic biomarkers that may contribute to the higher MAFLD prevalence and different disease severity in Latin America, where data is scarce. We compared the plasma and stool metabolomes, gene patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 single nucleotide polymorphism (SNP), diet, demographic and clinical data of 33 patients (12 simple steatosis and 21 steatohepatitis) and 19 healthy volunteers (HV). The potential predictive utility of the identified biomarkers for MAFLD diagnosis and progression was evaluated by logistic regression modelling and ROC curves. Twenty-four (22 in plasma and 2 in stool) out of 424 metabolites differed among groups. Plasma triglyceride (TG) levels were higher among MAFLD patients, whereas plasma phosphatidylcholine (PC) and lysoPC levels were lower among HV. The PNPLA3 risk genotype was related to higher plasma levels of eicosenoic acid or fatty acid 20:1 (FA(20:1)). Body mass index and plasma levels of PCaaC24:0, FA(20:1) and TG (16:1_34:1) showed the best AUROC for MAFLD diagnosis, whereas steatosis and steatohepatitis could be discriminated with plasma levels of PCaaC24:0 and PCaeC40:1. This study identified for the first time MAFLD potential non-invasive biomarkers in a Latin American population. The association of PNPLA3 genotype with FA(20:1) suggests a novel metabolic pathway influencing MAFLD pathogenesis.
Identifiants
pubmed: 34137937
doi: 10.1007/s11306-021-01810-6
pii: 10.1007/s11306-021-01810-6
doi:
Substances chimiques
Biomarkers
0
Membrane Proteins
0
Lipase
EC 3.1.1.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
58Références
Afdhal, N. H., & Nunes, D. (2004). Evaluation of liver fibrosis: A concise review. American Journal of Gastroenterology, 99(6), 1160–1174.
doi: 10.1111/j.1572-0241.2004.30110.x
Ahn, S. B., Jun, D. W., Kang, B. K., Lim, J. H., Lim, S., & Chung, M. J. (2019). Randomized, double-blind, placebo-controlled study of a multispecies probiotic mixture in nonalcoholic fatty liver disease. Scientific Reports, 9(1), 1–9.
Aragonès, G., González-García, S., Aguilar, C., Richart, C., & Auguet, T. (2019). Gut microbiota-derived mediators as potential markers in nonalcoholic fatty liver disease. BioMed Research International, 2019, 1–10.
doi: 10.1155/2019/8507583
Argamasilla, R., Roehring, C., & Koal, T. (2020). Metabolome and lipidome analysis of human fecal samples using the MxP® quant 500 kit. Application Note 35039 V2_02-2020. BIOCRATES Life Sciences AG, Innsbruck, Austria. Retrieved January 23, 2021 from https://biocrates.com/wp-content/uploads/2020/04/ApplicationNote_35039_Quant500_Feces_V2.pdf
Asociación Argentina para el Estudio de las Enfermedades del Hígado. (2019). Primer Guía de Diagnóstico y Tratamiento del Hígado Graso No Alcohólico de la Asociación Argentina para el Estudio de las Enfermedades del Hígado. Retrieved January 23, 2021 from https://www.aaeeh.org.ar/es/attachment/show/40
Berná, G., & Romero-Gomez, M. (2020). The role of nutrition in non-alcoholic fatty liver disease: Pathophysiology and management. Liver International, 40(Suppl 1), 102–108.
pubmed: 32077594
doi: 10.1111/liv.14360
pmcid: 32077594
Biagi, E., Nylund, L., Candela, M., Ostan, R., Bucci, L., Pini, E., Nikkïla, J., Monti, D., Satokari, R., Franceschi, C., Brigidi, P., & De Vos, W. (2010). Through ageing, and beyond: Gut microbiota and inflammatory status in seniors and centenarians. PLoS ONE, 5(5), e10667.
pubmed: 20498852
pmcid: 2871786
doi: 10.1371/journal.pone.0010667
Blachier, F., Beaumont, M., & Kim, E. (2019). Cysteine-derived hydrogen sulfide and gut health: A matter of endogenous or bacterial origin. Current Opinion in Clinical Nutrition & Metabolic Care, 22(1), 68–75.
doi: 10.1097/MCO.0000000000000526
Buzzetti, E., Pinzani, M., & Tsochatzis, E. A. (2016). The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism, 65(8), 1038–1048.
pubmed: 26823198
doi: 10.1016/j.metabol.2015.12.012
pmcid: 26823198
Caussy, C., & Loomba, R. (2018). Gut microbiome, microbial metabolites and the development of NAFLD. Nature Reviews Gastroenterology & Hepatology, 15(12), 719–720.
doi: 10.1038/s41575-018-0058-x
Chong, J., Soufan, O., Li, C., Caraus, I., Li, S., Bourque, G., Wishart, D. S., & Xia, J. (2018). MetaboAnalyst 4.0: Towards more transparent and integrative metabolomics analysis. Nucleic Acids Research, 46(W1), W486-494.
pubmed: 29762782
pmcid: 6030889
doi: 10.1093/nar/gky310
Da Silva, H. E., Teterina, A., Comelli, E. M., Taibi, A., Arendt, B. M., Fischer, S. E., Lou, W., & Allard, J. P. (2018). Nonalcoholic fatty liver disease is associated with dysbiosis independent of body mass index and insulin resistance. Scientific Reports, 8(1), 1–12.
pubmed: 29311619
pmcid: 5758755
Dehingia, M., Adak, A., & Khan, M. R. (2019). Ethnicity-influenced microbiota: A future healthcare perspective. Trends in Microbiology, 27(3), 191–193.
pubmed: 30685243
doi: 10.1016/j.tim.2019.01.002
pmcid: 30685243
de la Cuesta-Zuluaga, J., Kelley, S. T., Chen, Y., Escobar, J. S., Mueller, N. T., Ley, R. E., McDonald, D., Huang, S., Swafford, A. D., Knight, R., & Thackray, V. G. (2019). Age- and sex-dependent patterns of gut microbial diversity in human adults. mSystems, 4(4), e00261-19.
pubmed: 31098397
pmcid: 6517691
Delzenne, N. M., Knudsen, C., Beaumont, M., Rodriguez, J., Neyrinck, A. M., & Bindels, L. B. (2019). Contribution of the gut microbiota to the regulation of host metabolism and energy balance: A focus on the gut-liver axis. Proceedings of the Nutrition Society, 78(3), 319–328.
doi: 10.1017/S0029665118002756
Ekstedt, M., Hagström, H., Nasr, P., Fredrikson, M., Stål, P., Kechagias, S., & Hultcrantz, R. (2015). Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology, 61(5), 1547–1554.
pubmed: 25125077
doi: 10.1002/hep.27368
pmcid: 25125077
Enooku, K., Nakagawa, H., Fujiwara, N., Kondo, M., Minami, T., Hoshida, Y., Shibahara, J., Tateishi, R., & Koike, K. (2019). Altered serum acylcarnitine profile is associated with the status of nonalcoholic fatty liver disease (NAFLD) and NAFLD-related hepatocellular carcinoma. Scientific Reports, 9(1), 1–9.
doi: 10.1038/s41598-019-47216-2
Eslam, M., Newsome, P. N., Sarin, S. K., Anstee, Q. M., Targher, G., Romero-Gomez, M., Zelber-Sagi, S., Wai-Sun Wong, V., Dufour, J. F., Schattenberg, J. M., Kawaguchi, T., Arrese, M., Valenti, L., Shiha, G., Tiribelli, C., Yki-Järvinen, H., Fan, J. G., Grønbæk, H., Yilmaz, Y., & George, J. (2020). A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. Journal of Hepatology, 73(1), 202–209.
pubmed: 32278004
doi: 10.1016/j.jhep.2020.03.039
pmcid: 32278004
Farrell, G. C. (2010). PNPLeAse get the fats right: Does lipogenesis or lipolysis cause NASH? Hepatology, 52(3), 818–821.
pubmed: 20812356
doi: 10.1002/hep.23867
pmcid: 20812356
Gunn, N. T., & Shiffman, M. L. (2018). The use of liver biopsy in nonalcoholic fatty liver disease: When to biopsy and in whom. Clinical Liver Disease, 22(1), 109–119.
doi: 10.1016/j.cld.2017.08.006
Guohong-Liu, Q.-Z., & Hongyun-Wei. . (2019). Characteristics of intestinal bacteria with fatty liver diseases and cirrhosis. Annals of Hepatology, 18(6), 796–803.
pubmed: 31558417
doi: 10.1016/j.aohep.2019.06.020
pmcid: 31558417
Guo, Z., Zhang, J., Wang, Z., Ang, K. Y., Huang, S., Hou, Q., Su, X., Qiao, J., Zheng, Y., Wang, L., Koh, E., Danliang, H., Xu, J., Lee, Y. K., & Zhang, H. (2016). Intestinal microbiota distinguish gout patients from healthy humans. Scientific Reports, 6, 1–10.
doi: 10.1038/s41598-016-0001-8
Hadizadeh, F., Faghihimani, E., & Adibi, P. (2017). Nonalcoholic fatty liver disease: Diagnostic biomarkers. World Journal of Gastrointestinal Pathophysiology, 8(2), 11.
pubmed: 28573064
pmcid: 5437499
doi: 10.4291/wjgp.v8.i2.11
Haug, K., Cochrane, K., Nainala, V. C., Williams, M., Chang, J., Jayaseelan, K. V., & O’Donovan, C. (2020). MetaboLights: A resource evolving in response to the needs of its scientific community. Nucleic Acids Research, 48(D1), D440–D444.
pubmed: 31691833
pmcid: 31691833
Hoyles, L., Fernández-Real, J. M., Federici, M., Serino, M., Abbott, J., Charpentier, J., Heymes, C., Luque, J. L., Anthony, E., Barton, R. H., Chilloux, J., Myridakis, A., Martinez-Gili, L., Moreno-Navarrete, J. M., Benhamed, F., Azalbert, V., Blasco-Baque, V., Puig, J., Xifra, G., & Dumas, M. E. (2018). Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women. Nature Medicine, 24(7), 1070–1080.
pubmed: 29942096
pmcid: 6140997
doi: 10.1038/s41591-018-0061-3
Jarido, V., Kennedy, L., Hargrove, L., Demieville, J., Thomson, J., Stephenson, K., & Francis, H. (2017). The emerging role of mast cells in liver disease. American Journal of Physiology Gastrointestinal and Liver Physiology, 313(2), G89–G101.
pubmed: 28473331
pmcid: 5582878
doi: 10.1152/ajpgi.00333.2016
Kalhan, S. C., Guo, L., Edmison, J., Dasarathy, S., McCullough, A. J., Hanson, R. W., & Milburn, M. (2011). Plasma metabolomic profile in nonalcoholic fatty liver disease. Metabolism, 60(3), 404–413.
pubmed: 20423748
doi: 10.1016/j.metabol.2010.03.006
pmcid: 20423748
Kim, D., & Kim, W. R. (2017). Nonobese fatty liver disease. Clinical Gastroenterology and Hepatology, 15(4), 474–485.
pubmed: 27581063
doi: 10.1016/j.cgh.2016.08.028
pmcid: 27581063
Kim, D. J., Yoon, S., Ji, S. C., Yang, J., Kim, Y. K., Lee, S., Yu, K. S., Jang, I. J., Chung, J. Y., & Cho, J. Y. (2018). Ursodeoxycholic acid improves liver function via phenylalanine/tyrosine pathway and microbiome remodelling in patients with liver dysfunction. Scientific Reports, 8(1), 1–11.
Kolodziejczyk, A. A., Zheng, D., Shibolet, O., & Elinav, E. (2019). The role of the microbiome in NAFLD and NASH. EMBO Molecular Medicine, 11(2), 1–13.
doi: 10.15252/emmm.201809302
Li, H., Wang, L., Yan, X., Liu, Q., Yu, C., Wei, H., Li, Y., Zhang, X., He, F., & Jiang, Y. (2011). A proton nuclear magnetic resonance metabonomics approach for biomarker discovery in nonalcoholic fatty liver disease. Journal of Proteome Research, 10(6), 2797–2806.
pubmed: 21563774
doi: 10.1021/pr200047c
pmcid: 21563774
Li, Q., Dhyani, M., Grajo, J. R., Sirlin, C., & Samir, A. E. (2018). Current status of imaging in nonalcoholic fatty liver disease. World Journal of Hepatology, 10(8), 530–542.
pubmed: 30190781
pmcid: 6120999
doi: 10.4254/wjh.v10.i8.530
Liu, R., Hong, J., Xu, X., Feng, Q., Zhang, D., Gu, Y., Shi, J., Zhao, S., Liu, W., Wang, X., Xia, H., Liu, Z., Cui, B., Liang, P., Xi, L., Jin, J., Ying, X., Wang, X., Zhao, X., & Wang, W. (2017). Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention. Nature Medicine, 23(7), 859–868.
pubmed: 28628112
doi: 10.1038/nm.4358
pmcid: 28628112
Martínez, L. A., Larrieta, E., Calva, J. J., Kershenobich, D., & Torre, A. (2017). The expression of PNPLA3 polymorphism could be the key for severe liver disease in NAFLD in hispanic population. Annals of Hepatology, 16(6), 909–915.
pubmed: 29055919
doi: 10.5604/01.3001.0010.5282
pmcid: 29055919
Mazo, D. F., Malta, F. M., Stefano, J. T., Salles, A. P. M., Gomes-Gouvea, M. S., Nastri, A. C. S., Almeida, J. R., Pinho, J. R. R., Carrilho, F. J., & Oliveira, C. P. (2019). Validation of PNPLA3 polymorphisms as risk factor for NAFLD and liver fibrosis in an admixed population. Annals of Hepatology, 18(3), 466–471.
pubmed: 31054980
doi: 10.1016/j.aohep.2018.10.004
pmcid: 31054980
Moosmang, S., Pitscheider, M., Sturm, S., Seger, C., Tilg, H., Halabalaki, M., & Stuppner, H. (2019). Metabolomic analysis—Addressing NMR and LC-MS related problems in human feces sample preparation. Clinica Chimica Acta, 489, 169–176.
doi: 10.1016/j.cca.2017.10.029
Nishitsuji, K., Xiao, J., Nagatomo, R., Umemoto, H., Morimoto, Y., Akatsu, H., Inoue, K., & Tsuneyama, K. (2017). Analysis of the gut microbiome and plasma short-chain fatty acid profiles in a spontaneous mouse model of metabolic syndrome. Scientific Reports, 7(1), 15876.
pubmed: 29158587
pmcid: 5696507
doi: 10.1038/s41598-017-16189-5
Nyamundanda, G., Gormley, I. C., Fan, Y., Gallagher, W. M., & Brennan, L. (2013). MetSizeR: Selecting the optimal sample size for metabolomic studies using an analysis based approach. BMC Bioinformatics, 14, 338.
pubmed: 24261687
pmcid: 4222287
doi: 10.1186/1471-2105-14-338
Okamura, T., Hashimoto, Y., Hamaguchi, M., Obora, A., Kojima, T., & Fukui, M. (2020). Creatinine-to-bodyweight ratio is a predictor of incident non-alcoholic fatty liver disease: A population-based longitudinal study. Hepatology Research, 50(1), 57–66.
pubmed: 31692179
doi: 10.1111/hepr.13429
pmcid: 31692179
Pan, L., Han, P., Ma, S., Peng, R., Wang, C., Kong, W., Cong, L., Fu, J., Zhang, Z., Yu, H., Wang, Y., & Jiang, J. (2020). Abnormal metabolism of gut microbiota reveals the possible molecular mechanism of nephropathy induced by hyperuricemia. Acta Pharmaceutica Sinica B, 10(2), 249–261.
pubmed: 32082971
doi: 10.1016/j.apsb.2019.10.007
pmcid: 32082971
Perttilä, J., Huaman-Samanez, C., Caron, S., Tanhuanpää, K., Staels, B., Yki-Järvinen, H., & Olkkonen, V. M. (2012). PNPLA3 is regulated by glucose in human hepatocytes, and its I148M mutant slows down triglyceride hydrolysis. American Journal of Physiology-Endocrinology and Metabolism, 302(9), E1063–E1069.
pubmed: 22338072
doi: 10.1152/ajpendo.00125.2011
pmcid: 22338072
Souza, P. M., de Oliveira, C., Pinchemel Cotrim, H., & Arrese, M. (2019). Nonalcoholic fatty liver disease risk factors in Latin American populations: Current scenario and perspectives. Clinical Liver Disease, 13(2), 39–42.
doi: 10.1002/cld.759
Pontoriero, A. C., Trinks, J., Hulaniuk, M. L., Caputo, M., Fortuny, L., Pratx, L. B., Frías, A., Torres, O., Nuñez, F., Gadano, A., Argibay, P., Corach, D., & Flichman, D. (2015). Influence of ethnicity on the distribution of genetic polymorphisms associated with risk of chronic liver disease in South American populations. BMC Genetics, 16, 1–8.
doi: 10.1186/s12863-015-0255-3
Quesada-Vázquez, S., Aragonès, G., Del Bas, J. M., & Escoté, X. (2020). Diet, gut microbiota and non-alcoholic fatty liver disease: Three parts of the same axis. Cells, 9(1), 176.
pmcid: 7016763
doi: 10.3390/cells9010176
R Core Team. (2020). R: A language and environment for statistical computing. Vienna, Austria. Retrieved January 23, 2021 from https://www.r-project.org/
Rinninella, E., Raoul, P., Cintoni, M., Franceschi, F., Miggiano, G. A. D., Gasbarrini, A., & Mele, M. C. (2019). What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms, 7(1), 14.
pmcid: 6351938
doi: 10.3390/microorganisms7010014
Rodríguez, I. T., Ballart, J. F., Pastor, G. C., Jordà, E. B., & Val, V. A. (2008). Validation of a short questionnaire on frequency of dietary intake: Reproducibility and validity. Nutrición Hospitalaria, 23(3), 242–252.
pubmed: 18560701
pmcid: 18560701
Sayiner, M., & Younossi, Z. M. (2019). Nonalcoholic steatohepatitis is becoming a top indication for liver transplantation worldwide. Liver Transplantation, 25(1), 10–11.
pubmed: 30472779
doi: 10.1002/lt.25387
pmcid: 30472779
Sheka, A. C., Adeyi, O., Thompson, J., Hameed, B., Crawford, P. A., & Ikramuddin, S. (2020). Nonalcoholic steatohepatitis: A review. JAMA - Journal of the American Medical Association, 323(12), 1175–1183.
pubmed: 32207804
doi: 10.1001/jama.2020.2298
pmcid: 32207804
Singh, R. K., Chang, H. W., Yan, D., Lee, K. M., Ucmak, D., Wong, K., Abrouk, M., Farahnik, B., Nakamura, M., Zhu, T. H., Bhutani, T., & Liao, W. (2017). Influence of diet on the gut microbiome and implications for human health. Journal of Translational Medicine, 15(1), 73.
pubmed: 28388917
pmcid: 5385025
doi: 10.1186/s12967-017-1175-y
Singh, S. P., & Barik, R. K. (2020). NonInvasive biomarkers in nonalcoholic fatty liver disease: Are we there yet? Journal of Clinical and Experimental Hepatology, 10(1), 88–98.
pubmed: 32025168
doi: 10.1016/j.jceh.2019.09.006
pmcid: 32025168
Sookoian, S., & Pirola, C. J. (2019). Genetics of nonalcoholic fatty liver disease: From pathogenesis to therapeutics. Seminars in Liver Disease, 39(2), 124–140.
pubmed: 30912099
doi: 10.1055/s-0039-1679920
pmcid: 30912099
Stremmel, W., Schmidt, K. V., Schuhmann, V., Kratzer, F., Garbade, S. F., Langhans, C. D., Fricker, G., & Okun, J. G. (2017). Blood trimethylamine-n-oxide originates from microbiota mediated breakdown of phosphatidylcholine and absorption from small intestine. PLoS ONE, 12(1), 1–9.
doi: 10.1371/journal.pone.0170742
Sumida, Y., Nakajima, A., & Itoh, Y. (2014). Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World Journal of Gastroenterology, 20(2), 475–485.
pubmed: 24574716
pmcid: 3923022
doi: 10.3748/wjg.v20.i2.475
Tiwari-Heckler, S., Gan-Schreier, H., Stremmel, W., Chamulitrat, W., & Pathil, A. (2018). Circulating phospholipid patterns in NAFLD patients associated with a combination of metabolic risk factors. Nutrients, 10(5), 649.
pmcid: 5986528
doi: 10.3390/nu10050649
Trépo, E., Romeo, S., Zucman-Rossi, J., & Nahon, P. (2016). PNPLA3 gene in liver diseases. Journal of Hepatology, 65(2), 399–412.
pubmed: 27038645
doi: 10.1016/j.jhep.2016.03.011
pmcid: 27038645
van der Veen, J. N., Kennelly, J. P., Wan, S., Vance, J. E., Vance, D. E., & Jacobs, R. L. (2017). The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease. Biochimica et Biophysica Acta - Biomembranes, 1859(9 Pt B), 1558–1572.
pubmed: 28411170
doi: 10.1016/j.bbamem.2017.04.006
pmcid: 28411170
Velasco, P., Ferreira, A., Crovesy, L., & Marine, T. (2012). Fatty acids, gut microbiota, and the genesis of obesity. In V. Waisundara (Ed.), Biochemistry and health benefits of fatty acids (p. 13). IntechOpen.
Vernon, G., Baranova, A., & Younossi, Z. M. (2011). Systematic review: The epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Alimentary Pharmacology & Therapeutics, 34(3), 274–285.
doi: 10.1111/j.1365-2036.2011.04724.x
Wierzbicki, A. S., & Oben, J. (2012). Nonalcoholic fatty liver disease and lipids. Current Opinion in Lipidology, 23(4), 345–352.
pubmed: 22617751
doi: 10.1097/MOL.0b013e3283541cfc
pmcid: 22617751
Wong, V. W. S., Adams, L. A., de Lédinghen, V., Wong, G. L. H., & Sookoian, S. (2018). Noninvasive biomarkers in NAFLD and NASH—Current progress and future promise. Nature Reviews Gastroenterology & Hepatology, 15(8), 461–478.
doi: 10.1038/s41575-018-0014-9
Xu, C., Wan, X., Xu, L., Weng, H., Yan, M., Miao, M., Sun, Y., Xu, G., Dooley, S., Li, Y., & Yu, C. (2015). Xanthine oxidase in non-alcoholic fatty liver disease and hyperuricemia: One stone hits two birds. Journal of Hepatology, 62(6), 1412–1419.
pubmed: 25623823
doi: 10.1016/j.jhep.2015.01.019
pmcid: 25623823
Xu, C. (2016). Hyperuricemia and nonalcoholic fatty liver disease: From bedside to bench and back. Hepatology International, 10(2), 286–293.
pubmed: 26671825
doi: 10.1007/s12072-015-9682-5
pmcid: 26671825
Yasuda, S., Okahashi, N., Tsugawa, H., Ogata, Y., Ikeda, K., Suda, W., Arai, H., Hattori, M., & Arita, M. (2020). Elucidation of gut microbiota-associated lipids using LC-MS/MS and 16S rRNA sequence analyses. iScience, 23(12), 101841.
pubmed: 33313490
pmcid: 7721639
doi: 10.1016/j.isci.2020.101841
Younossi, Z., Tacke, F., Arrese, M., Chander Sharma, B., Mostafa, I., Bugianesi, E., Wai-Sun Wong, V., Yilmaz, Y., George, J., Fan, J., & Vos, M. B. (2019). Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology, 69(6), 2672–2682.
pubmed: 30179269
doi: 10.1002/hep.30251
pmcid: 30179269
Yu, M., Zhu, Y., Cong, Q., & Wu, C. (2017). Metabonomics research progress on liver diseases. Canadian Journal of Gastroenterology & Hepatology, 2017, 8467192.
doi: 10.1155/2017/8467192
Zhgun, E. S., & Ilina, E. N. (2020). Fecal metabolites as non-invasive biomarkers of gut diseases. Acta Naturae, 12(2), 4–14.
pubmed: 32742723
pmcid: 7385093
doi: 10.32607/actanaturae.11151
Zhou, Y., Orešič, M., Leivonen, M., Gopalacharyulu, P., Hyysalo, J., Arola, J., Verrijken, A., Francque, S., Van Gaal, L., Hyötyläinen, T., & Yki-Järvinen, H. (2016). Noninvasive detection of nonalcoholic steatohepatitis using clinical markers and circulating levels of lipids and metabolites. Clinical Gastroenterology and Hepatology, 14(10), 1463-1472.e6.
pubmed: 27317851
doi: 10.1016/j.cgh.2016.05.046
pmcid: 27317851
Zhou, D., & Fan, J. G. (2019). Microbial metabolites in non-alcoholic fatty liver disease. World Journal of Gastroenterology, 25(17), 2019–2028.
pubmed: 31114130
pmcid: 6506577
doi: 10.3748/wjg.v25.i17.2019