Molecular-level host-microbe interactions: mechanisms, molecules, and modeling toward precision probiotics.

Area of Science:

• Microbiome research
• Molecular biology
• Immunology

Background:

• Next-generation probiotics (NGPs) offer precision therapeutic potential through specific molecular mechanisms.
• Understanding host-microbe molecular interactions is crucial for NGP efficacy.
• Microbe-derived molecules (MDMs) mediate targeted effects, distinct from broad-acting agents.

Purpose of the Study:

• To systematically review and organize knowledge on MDMs from NGPs.
• To classify MDMs based on their molecular interaction interfaces with hosts.
• To explore computational strategies for accelerating NGP therapeutic discovery.

Main Methods:

• Narrative review of recent peer-reviewed studies on host-microbe interactions and probiotic bioactives.
• Classification of MDMs based on protein-protein/peptide, protein-lipid/glycopeptide, and protein-metabolite interactions.
• Review of computational tools including molecular docking, simulations, and AI for interaction prediction.

Main Results:

• MDMs encompass proteins/peptides, lipids, glycoconjugates, and small metabolites.
• These molecules modulate host immune and metabolic pathways to maintain homeostasis.
• Computational approaches enhance the prediction of host-microbe interactions.

Conclusions:

• A framework integrating experimental and computational data can guide precision microbiome interventions.
• Targeted NGP therapies can be rationally designed for various disorders.
• This work supports the development of tailored NGP treatments for metabolic, inflammatory, infectious, and neurodegenerative diseases.