From “synthetic” to defined microbial communities for clearer terminology

Comment https://doi.org/10.1038/s41467-026-74251-1 From “synthetic” to defined microbial communities for clearer terminology 1234567890():,; 1234567890():,; Hanna Koch, Thomas Clavel, Cintia Mayr, Benjamin L. Coltman, Michael Schloter, Julia A. Vorholt, Yolanda Sanz, Tomislav Cernava, Gwyn A. Beattie, Lene Lange, Stéphane Chaillou, Ákos T. Kovács, Hauke Smidt, Corné M. J. Pieterse, Tanja Kostic, Omri M. Finkel, Christopher E. Lawson, Luca Cocolin, Jesús Mercado-Blanco, Robert D. Finn, Kalliope K. Papadopoulou, Matthew Ryan, Marco Candela, Paul D. Cotter, Gabriele Berg, Orla O’Sullivan, Manuel Delgado-Baquerizo, Pankaj Trivedi, Trevor C. Charles, Brajesh K. Singh, Günter Brader, Malek Marian & Angela Sessitsch Consortia of microbial isolates, also known as synthetic communities (SynComs), are increasingly used to study and harness microbemicrobe and microbe-host interactions. Since “synthetic” potentially evokes negative connotations, we propose adopting the term “Defined Microbial Community” for practical applications. Microbiomes are increasingly studied to drive medical, environmental, and biotechnological innovations. Understanding their functions and how to modulate them is a powerful tool in tackling global challenges related to food safety and security, climate change, ecological restoration, as well as animal and human health. In recent years, microbiome research and applications have undergone a conceptual transition. Early strategies focused on the application of single strains to modulate host or environmental outcomes. However, the limited ecological stability and efficacy of these approaches have prompted a shift towards more complex, yet defined, microbial consortia that better capture the taxonomic and functional microbiome diversity1 (Box 1). For example, the application of defined root-associated consortia to Arabidopsis thaliana and crop plants were shown to improve resilience and promote growth under biotic and abiotic stress2,3. Plant growth enhancing effects of multi-species consortia were also observed in field trials4. In humans, the shift from traditional probiotics to consortia-based formulations, also referred to as live biotherapeutics, marks a significant advancement in gut health5. BOX 1 Case studies on the application of microbial consortia in fundamental research and applied settings Plant microbiome—fundamental research Carlström and colleagues conducted drop-out and lateintroduction experiments by inoculating Arabidopsis thaliana with Defined Microbial Communities under gnotobiotic conditions (original publication: SynComs) derived from a resource of 62 native nature communications Check for updates bacterial strains, testing how arrival order shapes community structure in the phyllosphere27. The study aimed to understand the assembly rules governing the establishment of plant microbiota and to determine the extent to which microbial community members interact, specifically examining how priority effects shape phyllosphere community structure. The results showed that community assembly is historically contingent and subject to priority effects, with missing strains able to invade an already established microbiota to varying degrees, while the established community as a whole remained largely resistant to and unaffected by latecomers. System: Arabidopsis thaliana phyllosphere; scale gnotobiotic plant assays (axenic system with host and amended strains); complexity: 62 bacterial strains belonging to 42 genera; design: the strains are native phyllosphere isolates to capture the natural microbial diversity. Plant microbiome—microbial consortium application Fonseca-García and colleagues analyzed the impact of a Defined Microbial Community (original publication: SynCom) on the native rhizosphere community of sorghum as well as the host response to Defined Microbial Community application under both gnotobiotic and field conditions28. By this, the authors could evaluate strain growth patterns within the Defined Microbial Community under different growth conditions and effect of Defined Microbial Community application on the host phenotype with focus on potential drought stress resilience. The amendment of the Defined Microbial Community in the field impacted community composition without affecting the abundance patterns of its members within the native rhizosphere community. This community modulation impacted the plant transcriptome and resulted in an increase of plant biomass under normal irrigation condition. System: Sorghum bicolor rhizosphere; scale: in vitro (no host), gnotobiotic plant assays (sterile system with host) and in the field (native community with host); complexity: 57 bacterial strains belonging to 16 genera; design: strains were selected either based on network analysis or based on their ability to use sorghum exudates for growth. Human microbiome—fundamental research Becker and colleagues designed a Defined Microbial Community of human gut bacteria (SIHUMI) to recapitulate the main functions of the whole ecosystem29. They developed an experimental model that (2026)17:5283 | 1 Comment enhances reproducibility between studies and can be used as a backbone community amendable with additional strains to functionally investigate microbe-microbe and microbe-host interactions. Gnotobiotic rats colonized with SIHUMI shared several features of conventionally colonized animals: short-chain fatty acid production, mucin degradation, bilirubin metabolism, and responses to diet. In subsequent studies, the model community was used to investigate effects on diet-induced obesity and intestinal inflammation. System: human gut; scale: in vitro (no host) and gnotobiotic animals; complexity: 7 to 8 bacterial strains in the original model; design: strains were selected based on expert knowledge of their metabolism, interactions, and occurrence in the human gut. Human microbiome—microbial consortium application Louie and colleagues tested the effects of the Defined Microbial Community VE303 on the recurrence of Clostridioides difficile infection (CDI)30. The primary objective was to determine the recommended VE303 dosing for a phase 3 trial. High-dose application of VE303 significantly lowered recurrent CDI in high-risk adults. VE303 was well tolerated with mostly mild gastrointestinal adverse events, supporting progression to a larger phase 3 study to validate the results. System: human gut; scale: in vivo, phase 2, randomized, doubleblind, placebo-controlled, dose-ranging trial; complexity: 8 strains mostly Clostridium clusters IV, XIVa, and XVII; design: The strains were isolated from healthy human donors and tested in different mixtures in the cefoperazone mouse model of CDI. Intentionally assembled microbial communities are often referred to as synthetic communities (SynComs). Their design and use for studying community dynamics represent a convergence of ecological theory, systems biology, and translational research. As model systems, they enable (...truncated)