CORRELATION OF GUT MICROBIOTA PROFILE AND DECOMPENSATION OF LIVER FUNCTION
Abstract
Background. There exists a bilateral relationship between the gut microorganisms and the liver, the so-called "gut microbiota-liver" axis. With the progression of liver diseases and a decrease in liver function, there is a change in the qualitative and quantitative composition of the gut microbiota. Objective. To analyze the relationship between the gut microbiota profile and the level of bilirubin, albumin, and prothrombin in patients with liver cirrhosis. Material and methods. A prospective cohort single-center study of 79 hospitalized patients with liver cirrhosis was conducted, which included collection and low-temperature freezing of stool samples. High throughput sequencing was performed with the MiSeq genetic analyzer (Illumina, USA) using a protocol based on the analysis of variable regions of the 16s rRNA gene. The data was analyzed by using the Kraken2 algorithm and by calculating the Spearman correlation coefficient. The significance level of α is assumed to be 0.05. The study is registered in Clinicaltrials.gov (NCT05335213). Results. The gut microbiota in liver cirrhosis and decreased liver function is characterized by an increase in the density of potentially pathogenic taxa such as Proteobacteria, Synergistetes, and a decrease in the taxa of Bacteroidetes, Elusimicrobia, Verrucomicrobia, Aquificae, Candidatus Saccharibacteria, Thermotogae, Ignavibacteriae, which can be attributed to autochthonous. The indices of alpha diversity of the intestinal microbiota (Observed, Shannon, Simpson, Chao1) have no significant differences depending on the level of bilirubin, albumin, and prothrombin. Conclusion. The relationship between the gut microbiota and liver diseases is beyond doubt. With the progression of liver cirrhosis and a decrease in liver function, an increase in the number of pathogenic and a decrease in potentially beneficial taxa of the fecal microbiota is observed.
References
Maslennikov R, Ivashkin V, Efremova I, Alieva A, Kashuh E, Tsvetaeva E, Poluektova E, Shirokova E, Ivashkin K. Gut dysbiosis is associated with poorer long-term prognosis in cirrhosis. World J Hepatol. 2021;13(5):557-570. https://doi.org/10.4254/wjh.v13.i5.557.
Bajaj JS, Peña-Rodriguez M, La Reau A, Phillips W, Fuchs M, Davis BC, Sterling RK, Sikaroodi M, Fagan A, Shamsaddini A, Henseler Z, Ward T, Puri P, Lee H, Gillevet PM. Longitudinal transkingdom gut microbial approach towards decompensation in outpatients with cirrhosis. Gut. 2023;72(4):759-771. https://doi.org/10.1136/gutjnl-2022-328403.
Trebicka J, Macnaughtan J, Schnabl B, Shawcross DL, Bajaj JS. The microbiota in cirrhosis and its role in hepatic decompensation. J Hepatol. 2021;75 Suppl 1(Suppl 1):S67-S81. https://doi.org/10.1016/j.jhep.2020.11.013.
Solé C, Guilly S, Da Silva K, Llopis M, Le-Chatelier E, Huelin P, Carol M, Moreira R, Fabrellas N, De Prada G, Napoleone L, Graupera I, Pose E, Juanola A, Borruel N, Berland M, Toapanta D, Casellas F, Guarner F, Doré J, Solà E, Ehrlich SD, Ginès P. Alterations in gut microbiome in cirrhosis as assessed by quantitative metagenomics: relationship with acute-on-chronic liver failure and prognosis. Gastroenterology. 2021;160(1):206-218.e13. https://doi.org/10.1053/j.gastro.2020.08.054.
Yamamoto K, Honda T, Inukai Y, Yokoyama S, Ito T, Imai N, Ishizu Y, Nakamura M, Kawashima H. Identification of the microbiome associated with prognosis in patients with chronic liver disease. Microorganisms. 2024;12(3):610. https://doi.org/10.3390/microorganisms12030610.
Arab JP, Martin-Mateos RM, Shah VH. Gut-liver axis, cirrhosis and portal hypertension: the chicken and the egg. Hepatol Int. 2018;12(Suppl 1):24-33. https://doi.org/10.1007/s12072-017-9798-x.
Malaeva EG, Voropaev EV, Stoma IO. Bioraznoobrazie mikrobioty kishechnika i urobioty pri cirroze pecheni [Biodiversity of gut microbiota and urobiota in liver cirrhosis]. Klinicheskaya infektologiya i parazitologiya [Clinical infectology and parasitology]. 2022;11(4):295-306. https://doi.org/10.34883/PI.2022.11.4.023. https://elibrary.ru/vdxolz. (Russian).
Albhaisi SAM, Bajaj JS, Sanyal AJ. Role of gut microbiota in liver disease. Am J Physiol Gastrointest Liver Physiol. 2020;318(1):G84-G98. https://doi.org/10.1152/ajpgi.00118.2019.
You JJ, Qiu J, Li GN, Peng XM, Ma Y, Zhou CC, Fang SW, Huang RW, Xiao ZH. The relationship between gut microbiota and neonatal pathologic jaundice: A pilot case-control study. Front Microbiol. 2023;14:1122172. https://doi.org/10.3389/fmicb.2023.1122172.
Maslennikov R, Poluektova E, Zolnikova O, Sedova A, Kurbatova A, Shulpekova Y, Dzhakhaya N, Kardasheva S, Nadinskaia M, Bueverova E, Nechaev V, Karchevskaya A, Ivashkin V. Gut Microbiota and Bacterial Translocation in the Pathogenesis of Liver Fibrosis. Int J Mol Sci. 2023;24(22):16502. https://doi.org/10.3390/ijms242216502.
Wu Z, Zhou H, Liu D, Deng F. Alterations in the gut microbiota and the efficacy of adjuvant probiotic therapy in liver cirrhosis. Front Cell Infect Microbiol. 2023;13:1218552. https://doi.org/10.3389/fcimb.2023.1218552.
Tilg H, Adolph TE, Trauner M. Gut-liver axis: Pathophysiological concepts and clinical implications. Cell Metab. 2022;34(11):1700-1718. https://doi.org/10.1016/j.cmet.2022.09.017.
Smith ML, Wade JB, Wolstenholme J, Bajaj JS. Gut microbiome-brain-cirrhosis axis. Hepatology. 2024;80(2):465-485. https://doi.org/10.1097/HEP.0000000000000344.
Sharma SP, Gupta H, Kwon GH, Lee SY, Song SH, Kim JS, Park JH, Kim MJ, Yang DH, Park H, Won SM, Jeong JJ, Oh KK, Eom JA, Lee KJ, Yoon SJ, Ham YL, Baik GH, Kim DJ, Suk KT. Gut microbiome and metabolome signatures in liver cirrhosis-related complications. Clin Mol Hepatol. 2024;30(4):845-862. https://doi.org/10.3350/cmh.2024.0349.
Zhao F, An R, Wang L, Shan J, Wang X. Specific gut microbiome and serum metabolome changes in lung cancer patients. Front Cell Infect Microbiol. 2021;11:725284. https://doi.org/10.3389/fcimb.2021.725284.
Wang Z, Gao X, Zeng R, Wu Q, Sun H, Wu W, Zhang X, Sun G, Yan B, Wu L, Ren R, Guo M, Peng L, Yang Y. Сhanges of the gastric mucosal microbiome associated with histological stages of gastric carcinogenesis. Front Microbiol. 2020;11:997. https://doi.org/10.3389/fmicb.2020.00997.