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Elucidation of Prebiotics, Probiotics, Postbiotics, and Target from Gut Microbiota to Alleviate Obesity via Network Pharmacology Study

The metabolites produced by the gut microbiota have been reported as crucial agents against obesity; however, their key targets have not been revealed completely in complex microbiome systems. Hence, the aim of this study was to decipher promising prebiotics, probiotics, postbiotics, and more import...

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Autores principales: Oh, Ki-Kwang, Gupta, Haripriya, Min, Byeong-Hyun, Ganesan, Raja, Sharma, Satya Priya, Won, Sung-Min, Jeong, Jin-Ju, Lee, Su-Been, Cha, Min-Gi, Kwon, Goo-Hyun, Jeong, Min-Kyo, Hyun, Ji-Ye, Eom, Jung-A, Park, Hee-Jin, Yoon, Sang-Jun, Choi, Mi-Ran, 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/PMC9496669/
https://www.ncbi.nlm.nih.gov/pubmed/36139478
http://dx.doi.org/10.3390/cells11182903
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author Oh, Ki-Kwang
Gupta, Haripriya
Min, Byeong-Hyun
Ganesan, Raja
Sharma, Satya Priya
Won, Sung-Min
Jeong, Jin-Ju
Lee, Su-Been
Cha, Min-Gi
Kwon, Goo-Hyun
Jeong, Min-Kyo
Hyun, Ji-Ye
Eom, Jung-A
Park, Hee-Jin
Yoon, Sang-Jun
Choi, Mi-Ran
Kim, Dong Joon
Suk, Ki-Tae
author_facet Oh, Ki-Kwang
Gupta, Haripriya
Min, Byeong-Hyun
Ganesan, Raja
Sharma, Satya Priya
Won, Sung-Min
Jeong, Jin-Ju
Lee, Su-Been
Cha, Min-Gi
Kwon, Goo-Hyun
Jeong, Min-Kyo
Hyun, Ji-Ye
Eom, Jung-A
Park, Hee-Jin
Yoon, Sang-Jun
Choi, Mi-Ran
Kim, Dong Joon
Suk, Ki-Tae
author_sort Oh, Ki-Kwang
collection PubMed
description The metabolites produced by the gut microbiota have been reported as crucial agents against obesity; however, their key targets have not been revealed completely in complex microbiome systems. Hence, the aim of this study was to decipher promising prebiotics, probiotics, postbiotics, and more importantly, key target(s) via a network pharmacology approach. First, we retrieved the metabolites related to gut microbes from the gutMGene database. Then, we performed a meta-analysis to identify metabolite-related targets via the similarity ensemble approach (SEA) and SwissTargetPrediction (STP), and obesity-related targets were identified by DisGeNET and OMIM databases. After selecting the overlapping targets, we adopted topological analysis to identify core targets against obesity. Furthermore, we employed the integrated networks to microbiota–substrate–metabolite–target (MSMT) via R Package. Finally, we performed a molecular docking test (MDT) to verify the binding affinity between metabolite(s) and target(s) with the Autodock 1.5.6 tool. Based on holistic viewpoints, we performed a filtering step to discover the core targets through topological analysis. Then, we implemented protein–protein interaction (PPI) networks with 342 overlapping target, another subnetwork was constructed with the top 30% degree centrality (DC), and the final core networks were obtained after screening the top 30% betweenness centrality (BC). The final core targets were IL6, AKT1, and ALB. We showed that the three core targets interacted with three other components via the MSMT network in alleviating obesity, i.e., four microbiota, two substrates, and six metabolites. The MDT confirmed that equol (postbiotics) converted from isoflavone (prebiotics) via Lactobacillus paracasei JS1 (probiotics) can bind the most stably on IL6 (target) compared with the other four metabolites (3-indolepropionic acid, trimethylamine oxide, butyrate, and acetate). In this study, we demonstrated that the promising substate (prebiotics), microbe (probiotics), metabolite (postbiotics), and target are suitable for obsesity treatment, providing a microbiome basis for further research.
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spelling pubmed-94966692022-09-23 Elucidation of Prebiotics, Probiotics, Postbiotics, and Target from Gut Microbiota to Alleviate Obesity via Network Pharmacology Study Oh, Ki-Kwang Gupta, Haripriya Min, Byeong-Hyun Ganesan, Raja Sharma, Satya Priya Won, Sung-Min Jeong, Jin-Ju Lee, Su-Been Cha, Min-Gi Kwon, Goo-Hyun Jeong, Min-Kyo Hyun, Ji-Ye Eom, Jung-A Park, Hee-Jin Yoon, Sang-Jun Choi, Mi-Ran Kim, Dong Joon Suk, Ki-Tae Cells Hypothesis The metabolites produced by the gut microbiota have been reported as crucial agents against obesity; however, their key targets have not been revealed completely in complex microbiome systems. Hence, the aim of this study was to decipher promising prebiotics, probiotics, postbiotics, and more importantly, key target(s) via a network pharmacology approach. First, we retrieved the metabolites related to gut microbes from the gutMGene database. Then, we performed a meta-analysis to identify metabolite-related targets via the similarity ensemble approach (SEA) and SwissTargetPrediction (STP), and obesity-related targets were identified by DisGeNET and OMIM databases. After selecting the overlapping targets, we adopted topological analysis to identify core targets against obesity. Furthermore, we employed the integrated networks to microbiota–substrate–metabolite–target (MSMT) via R Package. Finally, we performed a molecular docking test (MDT) to verify the binding affinity between metabolite(s) and target(s) with the Autodock 1.5.6 tool. Based on holistic viewpoints, we performed a filtering step to discover the core targets through topological analysis. Then, we implemented protein–protein interaction (PPI) networks with 342 overlapping target, another subnetwork was constructed with the top 30% degree centrality (DC), and the final core networks were obtained after screening the top 30% betweenness centrality (BC). The final core targets were IL6, AKT1, and ALB. We showed that the three core targets interacted with three other components via the MSMT network in alleviating obesity, i.e., four microbiota, two substrates, and six metabolites. The MDT confirmed that equol (postbiotics) converted from isoflavone (prebiotics) via Lactobacillus paracasei JS1 (probiotics) can bind the most stably on IL6 (target) compared with the other four metabolites (3-indolepropionic acid, trimethylamine oxide, butyrate, and acetate). In this study, we demonstrated that the promising substate (prebiotics), microbe (probiotics), metabolite (postbiotics), and target are suitable for obsesity treatment, providing a microbiome basis for further research. MDPI 2022-09-16 /pmc/articles/PMC9496669/ /pubmed/36139478 http://dx.doi.org/10.3390/cells11182903 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
Gupta, Haripriya
Min, Byeong-Hyun
Ganesan, Raja
Sharma, Satya Priya
Won, Sung-Min
Jeong, Jin-Ju
Lee, Su-Been
Cha, Min-Gi
Kwon, Goo-Hyun
Jeong, Min-Kyo
Hyun, Ji-Ye
Eom, Jung-A
Park, Hee-Jin
Yoon, Sang-Jun
Choi, Mi-Ran
Kim, Dong Joon
Suk, Ki-Tae
Elucidation of Prebiotics, Probiotics, Postbiotics, and Target from Gut Microbiota to Alleviate Obesity via Network Pharmacology Study
title Elucidation of Prebiotics, Probiotics, Postbiotics, and Target from Gut Microbiota to Alleviate Obesity via Network Pharmacology Study
title_full Elucidation of Prebiotics, Probiotics, Postbiotics, and Target from Gut Microbiota to Alleviate Obesity via Network Pharmacology Study
title_fullStr Elucidation of Prebiotics, Probiotics, Postbiotics, and Target from Gut Microbiota to Alleviate Obesity via Network Pharmacology Study
title_full_unstemmed Elucidation of Prebiotics, Probiotics, Postbiotics, and Target from Gut Microbiota to Alleviate Obesity via Network Pharmacology Study
title_short Elucidation of Prebiotics, Probiotics, Postbiotics, and Target from Gut Microbiota to Alleviate Obesity via Network Pharmacology Study
title_sort elucidation of prebiotics, probiotics, postbiotics, and target from gut microbiota to alleviate obesity via network pharmacology study
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496669/
https://www.ncbi.nlm.nih.gov/pubmed/36139478
http://dx.doi.org/10.3390/cells11182903
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