Mucin-dependent transcriptional dynamics of Akkermansia muciniphila in co-culture with human colonic organoids.

Abstract

Akkermansia muciniphila, a mucin-degrading gut bacterium, contributes to intestinal homeostasis and metabolic disorders, yet its transcriptional response to human colonic mucin remains unclear. Here, we used human colonic organoids derived from either a healthy tissue (wild-type) or ATOH1-knockout lines lacking goblet cell differentiation. Co-culturing wild-type or ATOH1-knockout organoids with A. muciniphila followed by RNA-sequencing revealed distinct transcriptional profiles modulated by mucin availability, particularly affecting genes for growth and stress resistance. Notably, mucin degradation genes exhibited limited responses, contrasting with studies using porcine mucin, highlighting the specificity of human mucin interactions. Conversely, genes for mucin uptake and pili formation (e.g., Amuc_1100), which are crucial for host interaction, were upregulated with wild-type organoids. These results underscore the importance of using physiologically relevant human models. Our findings reveal A. muciniphila's adaptive gene regulation in response to human mucin, offering insights into host-microbe interactions shaped by the mucosal environment.