The Landscape of Type VI Secretion across Human Gut Microbiomes Reveals Its Role in Community Composition

Although gut microbiome composition is well defined, the mechanisms underlying community assembly remain poorly understood. Bacteroidales possess three genetic architectures (GA1–3) of the type VI secretion system (T6SS), an effector delivery pathway that mediates interbacterial competition. Here we define the distribution and role of GA1–3 in the human gut using metagenomic analysis. We find that adult microbiomes harbor limited effector and cognate immunity genes, suggesting selection for compatibility at the species (GA1 and GA2) and strain (GA3) levels. Bacteroides fragilis GA3 is known to mediate potent inter-strain competition, and we observe GA3 enrichment among strains colonizing infant microbiomes, suggesting competition early in life. Additionally, GA3 is associated with increased Bacteroides abundance, indicating that this system confers an advantage in Bacteroides-rich ecosystems. Collectively, these analyses uncover the prevalence of T6SS-dependent competition and reveal its potential role in shaping human gut microbial composition. The T6SS is an effector delivery system that mediates interbacterial competition. Using metagenomic analyses, Verster et al. investigate the prevalence and role of the T6SS in the human gut microbiome. They demonstrate that the T6SS mediates interactions between Bacteroides strains in the infant microbiome and between species in Bacteroides-rich environments.