Health Sciences 1.
Csősz, Csongor
Semmelweis University - Faculty of Health Sciences
Csősz Csongor1
1: Semmelweis University - Faculty of Health Sciences
Introduction
Intestinal epithelial dysfunction in Crohn's disease involves changes in enterocyte function, crucial for cellular responsiveness, epithelial integrity, and intestinal barrier state. Molecular connections between enterocytes and gut microbiota occur through several mechanisms; protein-protein interactions mediated by bacterial extracellular vesicles (EVs) are of increasing interest. Bacteroides thetaiotaomicron is a key, well-characterized member of the human gut microbiota associated with epithelial regulation and adaptive responses.
Aims
Our goal was to investigate the state-dependent pattern of human-microbiota protein-protein interactions associated with extracellular vesicles, with a particular focus on enterocytes in healthy populations and Crohn's disease patients.
Methods
We analyzed gene expression differences characteristic of enterocytes in Crohn's disease patients compared to healthy population patterns based on publicly available human transcriptomic data. To map human-microbiota interactions, we used the MicrobioLink pipeline, in which we predicted potential human targets for proteins associated with B. thetaiotaomicron extracellular vesicles. We linked human-microbiota protein-protein interactions to transcriptomic differences by embedding them in a human protein-protein interaction network, enabling the interpretation of the state-dependent network context of interactions in enterocytes.
Result
During the analysis, we identified a large number of bacterium-human protein-protein interactions in enterocytes that differed between Crohn's disease and healthy conditions. The interactions appeared in different network environments in the two groups, suggesting that B. thetaiotaomicron-associated human-microbiota interactions are rearranged in a state-dependent manner in enterocytes.
Conclusion
The integrative, network-based approach used is suitable for cell-specific and condition-dependent mapping of human-microbiota interactions. Our results may contribute to a better understanding of the molecular background of enterocyte dysfunction in Crohn's disease.
Funding
The Ministry of Culture and Innovation’s University Research Scholarship Programme with code number 2025-2.1.1-EKÖP-2025-00014 was created with the support of the National Research, Development and Innovation Fund.