Synthetic microbial communities: emerging live biotherapeutics for targeted gut microbiome modulation

Abstract

Gut microbiome dysbiosis causes various intestinal diseases. However, an undefined composition and potential biosafety risks limit the applicability of traditional fecal microbiota transplantation (FMT). Synthetic microbial communities (SynComs), which are compositionally defined and rationally designed emerging live biotherapeutics, offer a novel alternative to FMT. This review establishes strict boundaries between SynComs and traditional donor-derived preparations, comparatively evaluating "top-down" and "bottom-up" construction strategies. We explored the mechanisms underlying the SynComs-mediated synergistic restoration of intestinal homeostasis via direct targeted antagonism and modulation of the host immune network. Moreover, we systematically evaluated the current research landscape of SynComs in Clostridioides difficile infection, inflammatory bowel disease, and colorectal cancer. This review examines fundamental challenges, including host colonization resistance, chemistry, manufacturing, and control barriers, biosafety risks, and microbiokinetic regulatory frameworks, thereby addressing the translational gap. Our analysis of current literature provides a theoretical basis for the clinical translation of SynComs as emerging live biotherapeutics.