Clade-specific extracellular vesicles from Akkermansia muciniphila mediate competitive colonization via direct inhibition and immune stimulation.

Akkermansia muciniphila, a promising candidate for next-generation probiotics, exhibits significant genomic diversity, classified into several distinct clades (AmI to AmIV). Notably, a single Akkermansia clade tends to predominate within individual hosts, with co-occurrence of different clades being rare. The mechanisms driving such clade-specific exclusion remain unclear. Here, we show that extracellular vesicles (EVs) derived from AmII clade inhibit the growth of clade I (AmI), conferring a competitive advantage to AmII. Moreover, we observe clade-specific immunoglobulin A (IgA) responses, where AmII clade-specific IgAs, induced by EVs from AmII, facilitate niche occupancy and competitive exclusion of AmI. These findings provide insights into the competitive dynamics of A. muciniphila clades and suggest that future personalized microbiome interventions could be optimized by considering the clade composition of A. muciniphila in individual hosts.