Deciphering fungal-microbial interactions: From microscale experimental models to integrative systems biology.

Abstract

Fungal-microbial interactions drive key ecosystem functions and offer vast, untapped potential for the bio-economy. However, translating these natural consortia into controllable applications is hindered by the structural and metabolic complexity of the interplay. This review navigates the complexity landscape of these interactions, examining the technological trajectory from the mechanistic foundation of 1:1 dialogue to the rational design of synthetic consortia. We discuss the transition from static cultivation toward advanced microfluidic ("fungi-on-a-chip") and biomimetic platforms that resolve the spatial ecology across diverse environmental gradients. Beyond extracellular associations, we highlight the paradigm shift toward synthetic endosymbiosis, where precise interaction engineering enables the creation of novel endosymbiotic chassis. Furthermore, we examine how integrating multi-omics with artificial intelligence-driven phenotyping and genome-scale metabolic modeling can bridge the gap between mechanistic discovery and predictive design through integrative systems biology and design-build-test-learn cycles, enabling the rational engineering of fungal-microbial consortia. These approaches offer opportunities to iteratively optimize community composition, metabolic exchange, and functional performance, thereby connecting laboratory-scale discovery with ecosystem-level complexity. Despite these advances, further development and integration of these approaches are needed to improve the reproducibility, scalability, and controllability of fungal-microbial consortia for agriculture, environmental, and industrial applications.