Multi-omic analysis unveils biological pathways in peripheral immune system associated to minimal hepatic encephalopathy appearance in cirrhotic patients

Abstract Patients with liver cirrhosis may develop minimal hepatic encephalopathy (MHE) which affects their quality of life and life span. It has been proposed that a shift in peripheral inflammation triggers the appearance of MHE. However, the mechanisms involved in this immune system shift remain...

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Autores principales:	Teresa Rubio, Vicente Felipo, Sonia Tarazona, Roberta Pastorelli, Desamparados Escudero-García, Joan Tosca, Amparo Urios, Ana Conesa, Carmina Montoliu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dbe0975e446a4472953af02c8fc7c53a
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spelling	oai:doaj.org-article:dbe0975e446a4472953af02c8fc7c53a2021-12-02T13:51:06ZMulti-omic analysis unveils biological pathways in peripheral immune system associated to minimal hepatic encephalopathy appearance in cirrhotic patients10.1038/s41598-020-80941-72045-2322https://doaj.org/article/dbe0975e446a4472953af02c8fc7c53a2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80941-7https://doaj.org/toc/2045-2322Abstract Patients with liver cirrhosis may develop minimal hepatic encephalopathy (MHE) which affects their quality of life and life span. It has been proposed that a shift in peripheral inflammation triggers the appearance of MHE. However, the mechanisms involved in this immune system shift remain unknown. In this work we studied the broad molecular changes involved in the induction of MHE with the goal of identifying (1) altered genes and pathways in peripheral blood cells associated to the appearance of MHE, (2) serum metabolites and cytokines with modified levels in MHE patients and (3) MHE-regulated immune response processes related to changes in specific serum molecules. We adopted a multi-omic approach to profile the transcriptome, metabolome and a panel of cytokines of blood samples taken from cirrhotic patients with or without MHE. Transcriptomic analysis supports the hypothesis of alternations in the Th1/Th2 and Th17 lymphocytes cell populations as major drivers of MHE. Cluster analysis of serum molecules resulted in six groups of chemically similar compounds, suggesting that functional modules operate during the induction of MHE. Finally, the multi-omic integrative analysis suggested a relationship between cytokines CCL20, CX3CL1, CXCL13, IL-15, IL-22 and IL-6 with alteration in chemotaxis, as well as a link between long-chain unsaturated phospholipids and the increased fatty acid transport and prostaglandin production. We found altered immune pathways that may collectively contribute to the mild cognitive impairment phenotype in MHE. Our approach is able to combine extracellular and intracellular information, opening new insights to the understanding of the disease.Teresa RubioVicente FelipoSonia TarazonaRoberta PastorelliDesamparados Escudero-GarcíaJoan ToscaAmparo UriosAna ConesaCarmina MontoliuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Teresa Rubio Vicente Felipo Sonia Tarazona Roberta Pastorelli Desamparados Escudero-García Joan Tosca Amparo Urios Ana Conesa Carmina Montoliu Multi-omic analysis unveils biological pathways in peripheral immune system associated to minimal hepatic encephalopathy appearance in cirrhotic patients
description	Abstract Patients with liver cirrhosis may develop minimal hepatic encephalopathy (MHE) which affects their quality of life and life span. It has been proposed that a shift in peripheral inflammation triggers the appearance of MHE. However, the mechanisms involved in this immune system shift remain unknown. In this work we studied the broad molecular changes involved in the induction of MHE with the goal of identifying (1) altered genes and pathways in peripheral blood cells associated to the appearance of MHE, (2) serum metabolites and cytokines with modified levels in MHE patients and (3) MHE-regulated immune response processes related to changes in specific serum molecules. We adopted a multi-omic approach to profile the transcriptome, metabolome and a panel of cytokines of blood samples taken from cirrhotic patients with or without MHE. Transcriptomic analysis supports the hypothesis of alternations in the Th1/Th2 and Th17 lymphocytes cell populations as major drivers of MHE. Cluster analysis of serum molecules resulted in six groups of chemically similar compounds, suggesting that functional modules operate during the induction of MHE. Finally, the multi-omic integrative analysis suggested a relationship between cytokines CCL20, CX3CL1, CXCL13, IL-15, IL-22 and IL-6 with alteration in chemotaxis, as well as a link between long-chain unsaturated phospholipids and the increased fatty acid transport and prostaglandin production. We found altered immune pathways that may collectively contribute to the mild cognitive impairment phenotype in MHE. Our approach is able to combine extracellular and intracellular information, opening new insights to the understanding of the disease.
format	article
author	Teresa Rubio Vicente Felipo Sonia Tarazona Roberta Pastorelli Desamparados Escudero-García Joan Tosca Amparo Urios Ana Conesa Carmina Montoliu
author_facet	Teresa Rubio Vicente Felipo Sonia Tarazona Roberta Pastorelli Desamparados Escudero-García Joan Tosca Amparo Urios Ana Conesa Carmina Montoliu
author_sort	Teresa Rubio
title	Multi-omic analysis unveils biological pathways in peripheral immune system associated to minimal hepatic encephalopathy appearance in cirrhotic patients
title_short	Multi-omic analysis unveils biological pathways in peripheral immune system associated to minimal hepatic encephalopathy appearance in cirrhotic patients
title_full	Multi-omic analysis unveils biological pathways in peripheral immune system associated to minimal hepatic encephalopathy appearance in cirrhotic patients
title_fullStr	Multi-omic analysis unveils biological pathways in peripheral immune system associated to minimal hepatic encephalopathy appearance in cirrhotic patients
title_full_unstemmed	Multi-omic analysis unveils biological pathways in peripheral immune system associated to minimal hepatic encephalopathy appearance in cirrhotic patients
title_sort	multi-omic analysis unveils biological pathways in peripheral immune system associated to minimal hepatic encephalopathy appearance in cirrhotic patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/dbe0975e446a4472953af02c8fc7c53a
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Multi-omic analysis unveils biological pathways in peripheral immune system associated to minimal hepatic encephalopathy appearance in cirrhotic patients

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