Cargando…

Identification of Gut Microbiome Metabolites via Network Pharmacology Analysis in Treating Alcoholic Liver Disease

Alcoholic liver disease (ALD) is linked to a broad spectrum of diseases, including diabetes, hypertension, atherosclerosis, and even liver carcinoma. The ALD spectrum includes alcoholic fatty liver disease (AFLD), alcoholic hepatitis, and cirrhosis. Most recently, some reports demonstrated that the...

Descripción completa

Detalles Bibliográficos
Autores principales: Oh, Ki-Kwang, Choi, Ye-Rin, Gupta, Haripriya, Ganesan, Raja, Sharma, Satya Priya, Won, Sung-Min, Jeong, Jin-Ju, Lee, Su-Been, Cha, Min-Gi, Kwon, Goo-Hyun, Kim, Dong-Joon, Suk, Ki-Tae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316215/
https://www.ncbi.nlm.nih.gov/pubmed/35877448
http://dx.doi.org/10.3390/cimb44070224
_version_ 1784754755292102656
author Oh, Ki-Kwang
Choi, Ye-Rin
Gupta, Haripriya
Ganesan, Raja
Sharma, Satya Priya
Won, Sung-Min
Jeong, Jin-Ju
Lee, Su-Been
Cha, Min-Gi
Kwon, Goo-Hyun
Kim, Dong-Joon
Suk, Ki-Tae
author_facet Oh, Ki-Kwang
Choi, Ye-Rin
Gupta, Haripriya
Ganesan, Raja
Sharma, Satya Priya
Won, Sung-Min
Jeong, Jin-Ju
Lee, Su-Been
Cha, Min-Gi
Kwon, Goo-Hyun
Kim, Dong-Joon
Suk, Ki-Tae
author_sort Oh, Ki-Kwang
collection PubMed
description Alcoholic liver disease (ALD) is linked to a broad spectrum of diseases, including diabetes, hypertension, atherosclerosis, and even liver carcinoma. The ALD spectrum includes alcoholic fatty liver disease (AFLD), alcoholic hepatitis, and cirrhosis. Most recently, some reports demonstrated that the pathogenesis of ALD is strongly associated with metabolites of human microbiota. AFLD was the onset of disease among ALDs, the initial cause of which is alcohol consumption. Thus, we analyzed the significant metabolites of microbiota against AFLD via the network pharmacology concept. The metabolites from microbiota were retrieved by the gutMGene database; sequentially, AFLD targets were identified by public databases (DisGeNET, OMIM). The final targets were utilized for protein–protein interaction (PPI) networks and signaling pathway analyses. Then, we performed a molecular docking test (MDT) to verify the affinity between metabolite(s) and target(s) utilizing the Autodock 1.5.6 tool. From a holistic viewpoint, we integrated the relationships of microbiota-signaling pathways-targets-metabolites (MSTM) using the R Package. We identified the uppermost six key targets (TLR4, RELA, IL6, PPARG, COX-2, and CYP1A2) against AFLD. The PPI network analysis revealed that TLR4, RELA, IL6, PPARG, and COX-2 had equivalent degrees of value (4); however, CYP1A2 had no associations with the other targets. The bubble chart showed that the PI3K-Akt signaling pathway in nine signaling pathways might be the most significant mechanism with antagonistic functions in the treatment of AFLD. The MDT confirmed that Icaritin is a promising agent to bind stably to RELA (known as NF-Κb). In parallel, Bacterium MRG-PMF-1, the PI3K-Akt signaling pathway, RELA, and Icaritin were the most significant components against AFLD in MSTM networks. In conclusion, we showed that the Icaritin–RELA complex on the PI3K-Akt signaling pathway by bacterial MRG-PMF-1 might have promising therapeutic effects against AFLD, providing crucial evidence for further research.
format Online
Article
Text
id pubmed-9316215
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-93162152022-07-27 Identification of Gut Microbiome Metabolites via Network Pharmacology Analysis in Treating Alcoholic Liver Disease Oh, Ki-Kwang Choi, Ye-Rin Gupta, Haripriya Ganesan, Raja Sharma, Satya Priya Won, Sung-Min Jeong, Jin-Ju Lee, Su-Been Cha, Min-Gi Kwon, Goo-Hyun Kim, Dong-Joon Suk, Ki-Tae Curr Issues Mol Biol Hypothesis Alcoholic liver disease (ALD) is linked to a broad spectrum of diseases, including diabetes, hypertension, atherosclerosis, and even liver carcinoma. The ALD spectrum includes alcoholic fatty liver disease (AFLD), alcoholic hepatitis, and cirrhosis. Most recently, some reports demonstrated that the pathogenesis of ALD is strongly associated with metabolites of human microbiota. AFLD was the onset of disease among ALDs, the initial cause of which is alcohol consumption. Thus, we analyzed the significant metabolites of microbiota against AFLD via the network pharmacology concept. The metabolites from microbiota were retrieved by the gutMGene database; sequentially, AFLD targets were identified by public databases (DisGeNET, OMIM). The final targets were utilized for protein–protein interaction (PPI) networks and signaling pathway analyses. Then, we performed a molecular docking test (MDT) to verify the affinity between metabolite(s) and target(s) utilizing the Autodock 1.5.6 tool. From a holistic viewpoint, we integrated the relationships of microbiota-signaling pathways-targets-metabolites (MSTM) using the R Package. We identified the uppermost six key targets (TLR4, RELA, IL6, PPARG, COX-2, and CYP1A2) against AFLD. The PPI network analysis revealed that TLR4, RELA, IL6, PPARG, and COX-2 had equivalent degrees of value (4); however, CYP1A2 had no associations with the other targets. The bubble chart showed that the PI3K-Akt signaling pathway in nine signaling pathways might be the most significant mechanism with antagonistic functions in the treatment of AFLD. The MDT confirmed that Icaritin is a promising agent to bind stably to RELA (known as NF-Κb). In parallel, Bacterium MRG-PMF-1, the PI3K-Akt signaling pathway, RELA, and Icaritin were the most significant components against AFLD in MSTM networks. In conclusion, we showed that the Icaritin–RELA complex on the PI3K-Akt signaling pathway by bacterial MRG-PMF-1 might have promising therapeutic effects against AFLD, providing crucial evidence for further research. MDPI 2022-07-19 /pmc/articles/PMC9316215/ /pubmed/35877448 http://dx.doi.org/10.3390/cimb44070224 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Hypothesis
Oh, Ki-Kwang
Choi, Ye-Rin
Gupta, Haripriya
Ganesan, Raja
Sharma, Satya Priya
Won, Sung-Min
Jeong, Jin-Ju
Lee, Su-Been
Cha, Min-Gi
Kwon, Goo-Hyun
Kim, Dong-Joon
Suk, Ki-Tae
Identification of Gut Microbiome Metabolites via Network Pharmacology Analysis in Treating Alcoholic Liver Disease
title Identification of Gut Microbiome Metabolites via Network Pharmacology Analysis in Treating Alcoholic Liver Disease
title_full Identification of Gut Microbiome Metabolites via Network Pharmacology Analysis in Treating Alcoholic Liver Disease
title_fullStr Identification of Gut Microbiome Metabolites via Network Pharmacology Analysis in Treating Alcoholic Liver Disease
title_full_unstemmed Identification of Gut Microbiome Metabolites via Network Pharmacology Analysis in Treating Alcoholic Liver Disease
title_short Identification of Gut Microbiome Metabolites via Network Pharmacology Analysis in Treating Alcoholic Liver Disease
title_sort identification of gut microbiome metabolites via network pharmacology analysis in treating alcoholic liver disease
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316215/
https://www.ncbi.nlm.nih.gov/pubmed/35877448
http://dx.doi.org/10.3390/cimb44070224
work_keys_str_mv AT ohkikwang identificationofgutmicrobiomemetabolitesvianetworkpharmacologyanalysisintreatingalcoholicliverdisease
AT choiyerin identificationofgutmicrobiomemetabolitesvianetworkpharmacologyanalysisintreatingalcoholicliverdisease
AT guptaharipriya identificationofgutmicrobiomemetabolitesvianetworkpharmacologyanalysisintreatingalcoholicliverdisease
AT ganesanraja identificationofgutmicrobiomemetabolitesvianetworkpharmacologyanalysisintreatingalcoholicliverdisease
AT sharmasatyapriya identificationofgutmicrobiomemetabolitesvianetworkpharmacologyanalysisintreatingalcoholicliverdisease
AT wonsungmin identificationofgutmicrobiomemetabolitesvianetworkpharmacologyanalysisintreatingalcoholicliverdisease
AT jeongjinju identificationofgutmicrobiomemetabolitesvianetworkpharmacologyanalysisintreatingalcoholicliverdisease
AT leesubeen identificationofgutmicrobiomemetabolitesvianetworkpharmacologyanalysisintreatingalcoholicliverdisease
AT chamingi identificationofgutmicrobiomemetabolitesvianetworkpharmacologyanalysisintreatingalcoholicliverdisease
AT kwongoohyun identificationofgutmicrobiomemetabolitesvianetworkpharmacologyanalysisintreatingalcoholicliverdisease
AT kimdongjoon identificationofgutmicrobiomemetabolitesvianetworkpharmacologyanalysisintreatingalcoholicliverdisease
AT sukkitae identificationofgutmicrobiomemetabolitesvianetworkpharmacologyanalysisintreatingalcoholicliverdisease