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

Abstract

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.

The orchestration of Cornus kousa fruit and gut microbiota for anti- obesity via integrated pharmacological analysis based on metabolomics

“…Next, in AGE-RAGE signaling pathway in diabetic complications, equol from GM is the most stable ligand on IL6, considering that equol might be a potent agent against OB. Our previous study clari ed that equol converted by Lactobacillus paracasei JS1 can bind rmly to the active site on IL6 [43]. Additionally, our result has been shown that 2-Amino-8-[3-d-ribofuranosyl]imidazo[1,2-a]-s-triazin-4-one from CKF exhibited good binding score on CDC42.…”

New insight of chemical constituents in Persea americana fruit against obesity via integrated pharmacology

“…Obesity (OB) is a prominent global health issue associated with diverse comorbidities, including type 2 diabetes, hypertension, dyslipidemia, and even certain cancers. 1,2 Excessive calory is a main cause to obstruct the balance of body metabolism maintained intake, expenditure, and storage of energy. 3 A fundamental method to assess OB is the body mass index (BMI), an easily calculable value that describes the relationship between height and weight, BMI groups with more than 30 is categorized as OB.…”

“…Obesity (OB) is a prominent global health issue associated with diverse comorbidities, including type 2 diabetes, hypertension, dyslipidemia, and even certain cancers 1,2 . Excessive calory is a main cause to obstruct the balance of body metabolism maintained intake, expenditure, and storage of energy 3 .…”

The convergent application of metabolites from Avena sativa and gut microbiota to ameliorate non-alcoholic fatty liver disease: a network pharmacology study

“…Most recently, a merged GM and NP study was contributed to decode the roles of GM against diarrhea-predominant irritable bowel syndrome (IBS-D), indicating that eighteen GM with treatment of Chinese traditional medicine were critical components to alleviate IBS-D [ 24 ]. Furthermore, key SMs of alcoholic liver diseases (ALD) and NAFLD were deciphered with the NP analysis [ 25 , 26 ].…”