Experimental models for intestinal host-microbe interactions.

Area of Science:

• Gastroenterology
• Microbiome Research
• Translational Medicine

Background:

• The intestinal barrier maintains homeostasis through epithelial integrity, mucus, and immune signaling.
• Microbial metabolites like SCFAs, bile acids, and tryptophan derivatives regulate the barrier.
• Current experimental models lack the complexity to fully translate findings to human physiology.

Purpose of the Study:

• To conceptualize intestinal barrier failure as a sequential process.
• To critically evaluate existing in vitro and ex vivo models.
• To propose an integrative, human-relevant framework for studying the intestinal barrier.

Main Methods:

• Conceptualization of barrier failure stages: junctional remodeling, mucus depletion, immune-driven permeability.
• Critical evaluation of current experimental models, focusing on metabolic biases and reductionist designs.
• Proposal of a stepwise framework integrating microbial fermentation, epithelial systems, and human tissues.

Main Results:

• Existing models are limited by metabolic biases and reductionist designs, hindering predictive value.
• The primary bottleneck is the lack of integrative, human-relevant strategies, not model diversity.
• A proposed framework links microbial fermentation to host responses across biological scales.

Conclusions:

• Intestinal barrier failure is a sequential process influenced by microbial metabolites.
• Improved, integrative models are crucial for translating research to clinical applications.
• The proposed framework facilitates functionally predictive platforms for precision nutrition and therapeutics.