The fungus-growing termite is considered a distinct ecological niche because it involves a tripartite symbiosis between the termite host, gut microflora, and the fungus , which has led to the expansion of highly organized and complex societies among termite colonies. Tripartite symbiosis in fungus-growing termites may promote unique microbes with distinctive metabolic pathways that may serve as valuable resources for developing novel antimicrobial therapeutic options. Recent research on complex tripartite symbioses has revealed a plethora of previously unknown natural products that may have ecological roles in signaling, communication, or defense responses. Natural products produced by symbionts may act as crucial intermediaries between termites and their pathogens by providing direct protection through their biological activities. Herein, we review the state-of-the-art research on both microbes and natural products originated from fungus-growing termite tripartite symbiosis, highlighting the diversity of microbes and the uniqueness of natural product classes and their bioactivities. Additionally, we emphasize future research prospects on fungus-growing termite related microorganisms, with a particular focus on their potential roles in bioactive product discovery.
