Jourdain, LisaGu, Wenyu2025-05-262025-05-262025-05-232025-05-1610.1128/aem.00404-25https://infoscience.epfl.ch/handle/20.500.14299/250454WOS:00148923920000140377302Synthetic microbial communities (SynComs) are powerful tools for investigating microbial interactions and community assembly by focusing on minimal yet functionally representative members. Here, we will highlight key principles for designing SynComs, specifically emphasizing the anaerobic digestion (AD) microbiome for waste treatment and upcycling. The AD process has traditionally been used to reduce organic waste volume while producing biogas as a renewable energy source. Its microbiome features well-defined trophic layers and metabolic groups. There has been growing interest in repurposing the AD process to produce value-added products and chemical precursors, contributing to sustainable waste management and the goals of a circular economy. Optimizing the AD process requires a better understanding of microbial interactions and the influence of both biotic and abiotic parameters, where SynComs offer great promise. Focusing on AD microbiomes, we review the principles of SynComs' design, including keystone taxa and function, cross-feeding interactions, and metabolic redundancy, as well as how modeling approaches could guide SynComs design. Furthermore, we address practical considerations for working with AD SynComs and examine constructed SynComs designed for anaerobic waste digestion. Finally, we discuss the challenges associated with designing and applying SynComs to enhance our understanding of the AD process. This review aims to explore the use of synthetic communities in studying anaerobic digestion and highlights their potential for developing innovative biotechnological processes.Englishanaerobic digestionsynthetic communityresource recoverymethanogenesissyntrophyfermentationmicrobial interactiontext::journal::journal article::review article