Structure-Based Modeling of the Gut Bacteria–Host Interactome Through Statistical Analysis of Domain–Domain Associations Using Machine Learning

The gut microbiome, a complex ecosystem of microorganisms, plays a pivotal role in human health and disease. The gut microbiome’s influence extends beyond the digestive system to various organs, and its imbalance is linked to a wide range of diseases, including cancer and neurodevelopmental, inflamm...

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Main Authors: Despoina P. Kiouri, Georgios C. Batsis, Thomas Mavromoustakos, Alessandro Giuliani, Christos T. Chasapis
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:BioTech
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Online Access:https://www.mdpi.com/2673-6284/14/1/13
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author Despoina P. Kiouri
Georgios C. Batsis
Thomas Mavromoustakos
Alessandro Giuliani
Christos T. Chasapis
author_facet Despoina P. Kiouri
Georgios C. Batsis
Thomas Mavromoustakos
Alessandro Giuliani
Christos T. Chasapis
author_sort Despoina P. Kiouri
collection DOAJ
description The gut microbiome, a complex ecosystem of microorganisms, plays a pivotal role in human health and disease. The gut microbiome’s influence extends beyond the digestive system to various organs, and its imbalance is linked to a wide range of diseases, including cancer and neurodevelopmental, inflammatory, metabolic, cardiovascular, autoimmune, and psychiatric diseases. Despite its significance, the interactions between gut bacteria and human proteins remain understudied, with less than 20,000 experimentally validated protein interactions between the host and any bacteria species. This study addresses this knowledge gap by predicting a protein–protein interaction network between gut bacterial and human proteins. Using statistical associations between Pfam domains, a comprehensive dataset of over one million experimentally validated pan-bacterial–human protein interactions, as well as inter- and intra-species protein interactions from various organisms, were used for the development of a machine learning-based prediction method to uncover key regulatory molecules in this dynamic system. This study’s findings contribute to the understanding of the intricate gut microbiome–host relationship and pave the way for future experimental validation and therapeutic strategies targeting the gut microbiome interplay.
format Article
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institution Kabale University
issn 2673-6284
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publishDate 2025-02-01
publisher MDPI AG
record_format Article
series BioTech
spelling doaj-art-52d59bb452ed485d88902292c0d35afe2025-08-20T03:43:33ZengMDPI AGBioTech2673-62842025-02-011411310.3390/biotech14010013Structure-Based Modeling of the Gut Bacteria–Host Interactome Through Statistical Analysis of Domain–Domain Associations Using Machine LearningDespoina P. Kiouri0Georgios C. Batsis1Thomas Mavromoustakos2Alessandro Giuliani3Christos T. Chasapis4Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, GreeceInstitute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, GreeceLaboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15772 Athens, GreeceEnvironment and Health Department, Istituto Superiore di Sanità, 00161 Rome, ItalyInstitute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, GreeceThe gut microbiome, a complex ecosystem of microorganisms, plays a pivotal role in human health and disease. The gut microbiome’s influence extends beyond the digestive system to various organs, and its imbalance is linked to a wide range of diseases, including cancer and neurodevelopmental, inflammatory, metabolic, cardiovascular, autoimmune, and psychiatric diseases. Despite its significance, the interactions between gut bacteria and human proteins remain understudied, with less than 20,000 experimentally validated protein interactions between the host and any bacteria species. This study addresses this knowledge gap by predicting a protein–protein interaction network between gut bacterial and human proteins. Using statistical associations between Pfam domains, a comprehensive dataset of over one million experimentally validated pan-bacterial–human protein interactions, as well as inter- and intra-species protein interactions from various organisms, were used for the development of a machine learning-based prediction method to uncover key regulatory molecules in this dynamic system. This study’s findings contribute to the understanding of the intricate gut microbiome–host relationship and pave the way for future experimental validation and therapeutic strategies targeting the gut microbiome interplay.https://www.mdpi.com/2673-6284/14/1/13gut microbiomeprotein networksdomain interactionshost–bacteria interactionsmachine learning
spellingShingle Despoina P. Kiouri
Georgios C. Batsis
Thomas Mavromoustakos
Alessandro Giuliani
Christos T. Chasapis
Structure-Based Modeling of the Gut Bacteria–Host Interactome Through Statistical Analysis of Domain–Domain Associations Using Machine Learning
BioTech
gut microbiome
protein networks
domain interactions
host–bacteria interactions
machine learning
title Structure-Based Modeling of the Gut Bacteria–Host Interactome Through Statistical Analysis of Domain–Domain Associations Using Machine Learning
title_full Structure-Based Modeling of the Gut Bacteria–Host Interactome Through Statistical Analysis of Domain–Domain Associations Using Machine Learning
title_fullStr Structure-Based Modeling of the Gut Bacteria–Host Interactome Through Statistical Analysis of Domain–Domain Associations Using Machine Learning
title_full_unstemmed Structure-Based Modeling of the Gut Bacteria–Host Interactome Through Statistical Analysis of Domain–Domain Associations Using Machine Learning
title_short Structure-Based Modeling of the Gut Bacteria–Host Interactome Through Statistical Analysis of Domain–Domain Associations Using Machine Learning
title_sort structure based modeling of the gut bacteria host interactome through statistical analysis of domain domain associations using machine learning
topic gut microbiome
protein networks
domain interactions
host–bacteria interactions
machine learning
url https://www.mdpi.com/2673-6284/14/1/13
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AT georgioscbatsis structurebasedmodelingofthegutbacteriahostinteractomethroughstatisticalanalysisofdomaindomainassociationsusingmachinelearning
AT thomasmavromoustakos structurebasedmodelingofthegutbacteriahostinteractomethroughstatisticalanalysisofdomaindomainassociationsusingmachinelearning
AT alessandrogiuliani structurebasedmodelingofthegutbacteriahostinteractomethroughstatisticalanalysisofdomaindomainassociationsusingmachinelearning
AT christostchasapis structurebasedmodelingofthegutbacteriahostinteractomethroughstatisticalanalysisofdomaindomainassociationsusingmachinelearning