ena-STUDY-WUR-16-03-2017-13:45:03:097-142
Mechanistic study on trophic interaction between mucosal keystone species and butyrogenic gut commensals
Host glycans are paramount in regulating the symbiotic relationship between humans and their gut bacteria. The constant flux of host-secreted mucin at the mucosal layer creates a steady niche space for bacteria colonization. Mucin, characterized by complex molecular structure, exerts selective nutritional pressure for mucin-degrading bacteria. Mucin degradation by keystone species subsequently drives the local trophic chain and shapes mucosal microbial assembly a.k.a. mucobiome. This study investigates mucin-driven trophic interaction between the specialized mucin-degrader, Akkermansia muciniphila and butyrogenic gut commensals. Co-cultures of A. muciniphila with non-mucolytic butyrogens (Anaerostipes caccae and Eubacterium hallii) were grown in minimal media supplemented with pure mucin. Metabolites (HPLC) and meta-transcriptome (RNA-seq) were studied. Mucin degradation by A. muciniphila produced mucin-derived monosaccharides and metabolites (galactose, fucose, mannose, GlcNAc and acetate) for the growth of butyrogens (A. caccae and E. hallii) resulted in 2mM butyrate production. Interestingly, co-culture of A. muciniphila with E. hallii demonstrated mutual relationship, in which pseudovitamin B12 production by E. hallii facilitated propionate production by A. muciniphila. Cobalamin-dependent methylmalonyl-CoA mutase genes (Amuc_1983 and Amuc_1984) were upregulated in A. muciniphila monoculture, indicated the attempt by A. muciniphila to activate propionate production pathway by synthesizing more key catalytic enzymes. Differential analysis (DESeq2) showed the presence of butyrogens resulted in an altered transcriptional profile of A. muciniphila. E. hallii in particular, incurred high functional impact on A. muciniphila gene expression. Mucosal subpopulation driven by A. muciniphila could result in butyrate and propionate production. Deciphering the underlying mechanism of this microbial tropism is crucial for the understanding of mucosal health and pathophysiology.
Host glycans are paramount in regulating the symbiotic relationship between humans and their gut bacteria. The constant flux of host-secreted mucin at the mucosal layer creates a steady niche space for bacteria colonization. Mucin, characterized by complex molecular structure, exerts selective nutritional pressure for mucin-degrading bacteria. Mucin degradation by keystone species subsequently drives the local trophic chain and shapes mucosal microbial assembly a.k.a. mucobiome. This study investigates mucin-driven trophic interaction between the specialized mucin-degrader, Akkermansia muciniphila and butyrogenic gut commensals. Co-cultures of A. muciniphila with non-mucolytic butyrogens (Anaerostipes caccae and Eubacterium hallii) were grown in minimal media supplemented with pure mucin. Metabolites (HPLC) and meta-transcriptome (RNA-seq) were studied. Mucin degradation by A. muciniphila produced mucin-derived monosaccharides and metabolites (galactose, fucose, mannose, GlcNAc and acetate) for the growth of butyrogens (A. caccae and E. hallii) resulted in 2mM butyrate production. Interestingly, co-culture of A. muciniphila with E. hallii demonstrated mutual relationship, in which pseudovitamin B12 production by E. hallii facilitated propionate production by A. muciniphila. Cobalamin-dependent methylmalonyl-CoA mutase genes (Amuc_1983 and Amuc_1984) were upregulated in A. muciniphila monoculture, indicated the attempt by A. muciniphila to activate propionate production pathway by synthesizing more key catalytic enzymes. Differential analysis (DESeq2) showed the presence of butyrogens resulted in an altered transcriptional profile of A. muciniphila. E. hallii in particular, incurred high functional impact on A. muciniphila gene expression. Mucosal subpopulation driven by A. muciniphila could result in butyrate and propionate production. Deciphering the underlying mechanism of this microbial tropism is crucial for the understanding of mucosal health and pathophysiology.