Comparative Genomics Revealed Wide Intra-Species Genetic Heterogeneity and Lineage-Specific Genes of Akkermansia muciniphila

Akkermansia muciniphila has potential as a next-generation probiotic, but few previous studies attempted to analyze its intraspecies population diversity. In this study, we performed a comparative genomic analysis of 112 filtered genomes from the NCBI database. The populations formed three clades (A-C) on the phylogenetic tree, suggesting the existence of three genetic lineages though clades B and C were phylogenetically closer than clade A. The three clades also showed geographic-based clustering, different genetic characteristics, and clade-specific genes. Two putative functional genes (RecD2 and xerD) were specific to clade C due to genomic islands. These lineage-specific genes might be associated with differences in genomic features (number of phages/genomic islands, pan-core genome, recombination rate, genetic diversity) between genetic lineages. The carbohydrate utilization gene profile (particularly for glycolytic hydrolases and carbohydrate esterases) also varied between clades, suggesting different carbohydrate metabolism potential/requirements between genetic lineages. Our findings provide important implications for future research on A. muciniphila. IMPORTANCE Akkermansia muciniphila has been widely accepted as part of the next generation of probiotics. However, most current studies on A. muciniphila have focused on the application of type strain BAA835(T) in the treatment of diseases, while few studies have reported on the genomic specificity, population structure, and functional characteristics of A. muciniphila species. By comparing the genomes of 112 strains from NCBI which met the quality control conditions, we found that the A. muciniphila population could be divided into three main clades (clades A to C) and presented a certain regional aggregation. There are significant differences among the three clades in their genetic characteristics and functional genes (the type strain BAA835(T) was located in clade A), especially in genes related to carbohydrate metabolism. It should be mentioned that probiotics should be a concept at the strain level rather than at the gut species level, so the probiotic properties of A. muciniphila need to be carefully interpreted.