Developing spore-forming gut bacteria as model organisms

Anaerobic gut bacteria have highly evolved functions that promote transmission between human hosts. These include resilient spores produced by many Bacillota (formerly Firmicutes) bacteria, which are tolerant to extended ambient oxygen exposure. Recent culturing and genomic studies have revealed the taxonomic diversity of gut spore-formers and their prevalence in human populations. However, due to a reliance on spore-forming model organisms that are not representative of commensal gut bacteria, we still have a limited understanding of gut microbiome-specific sporulation processes and their underlying genetics. In this opinion article, we outline a rational path for development of new model organisms derived from commensal spore-forming gut bacteria in order to obtain fundamental insights into sporulation and to provide a discovery platform for novel probiotic or microbiome-based therapeutic development. © 2026 The Author(s)