Differential impact of glycoprotein glycosylation on Akkermansia muciniphila growth dynamics

Abstract

Akkermansia muciniphila, a pivotal symbiotic bacterium resident in the human gut mucosal layer, significantly influences the intricate balance between health and disease states. This organism primarily thrives on mucin, a glycoprotein constituting the mucosal layer's main structural component. Despite the recognized importance of mucin as a nutrient source for this bacterium, the specific contributions of its constituent protein and glycan chains to the probiotic effects of A. muciniphila remain unexplored. Herein, the individual and combined impacts of the protein backbone and O-linked glycans of mucin on bacterial growth are investigated. Traditional deglycosylation techniques, which tend to disrupt protein integrity, were bypassed by employing recombinant mucin variants, facilitating an accurate assessment. The present findings reveal that both protein and O-glycan components of mucin conspicuously foster A. muciniphila proliferation, with the O-glycans playing a paramount role. By assessing foodstuff glycoproteins as a nutritional source, a differential influence on A. muciniphila growth was observed, where glycan structures from milk and eggs exhibited a negligible or, in the case of milk, inhibitory effect. The study progresses to unravel the variations in A. muciniphila's response to different substrates through its exoglycosidase activity, alongside examining the growth modulation by distinct monosaccharide compositions and glycan chain structures. The present results show the complex interactions between A. muciniphila’s dietary interactions and underscore the necessity for in-depth studies focused on monosaccharide composition and glycan structural nuances to better comprehend their functional roles in A. muciniphila's probiotic activity.

Keywords

• akkermansia muciniphila
• mucin o-glycan
• foodstuff glycoproteins
• glycoprotein glycosylation
• probiotic function.