Deciphering the trophic interaction between Akkermansia muciniphila and the butyrogenic gut commensal Anaerostipes caccae using a metatranscriptomic approach

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 for bacterial colonization. Mucin degradation by keystone species subsequently shapes the microbial community. This study investigated the transcriptional response during mucin-driven trophic interaction between the specialised mucin-degrader Akkermansia muciniphila and a butyrogenic gut commensal Anaerostipes caccae. A. muciniphila monocultures and co-cultures with non-mucolytic A. caccae from the Lachnospiraceae family were grown anaerobically in minimal media supplemented with mucin. We analysed for growth, metabolites (HPLC analysis), microbial composition (quantitative reverse transcription PCR), and transcriptional response (RNA-seq). Mucin degradation by A. muciniphila supported the growth of A. caccae and concomitant butyrate production predominantly via the acetyl-CoA pathway. Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes. Two putative operons that encode for uncharacterised proteins and an efflux system, and several two-component systems were also differentially regulated. This indicated A. muciniphila changed its transcriptional regulation in response to A. caccae. This study provides insight to understand the mucin-driven microbial ecology using metatranscriptomics. Our findings show that the expression of mucolytic enzymes by A. muciniphila increases upon the presence of a community member. This could indicate its role as a keystone species that supports the microbial community in the mucosal environment by increasing the availability of mucin sugars.