In vitro colonisation of the distal colon by Akkermansia muciniphila is largely mucin and pH dependent.

Abstract

Host mucin is the main constituent of the mucus layer that covers the gut epithelium of the host, and an important source of glycans for the bacteria colonising the intestine. Akkermansia muciniphila is a mucin-degrading bacterium, abundant in the human gut, that is able to produce acetate and propionate during this degradation process. A. muciniphila has been correlated with human health in previous studies, but a mechanistic explanation is lacking. In this study, the main site of colonisation was characterised alongside additional conditions, such as differences in colon pH, prebiotic supplementation and variable mucin supply. To overcome the limitations of in vivo studies concerning variations in mucin availability and difficult access to proximal regions of the colon, a dynamic in vitro gut model (SHIME) was used. In this model, A. muciniphila was found to colonise the distal colon compartment more abundantly than the proximal colon ((±8 log copies/ml compared to ±4 log copies/ml) and the preference for the distal compartment was found to be pH-dependent. The addition of mucin caused a specific increase of A. muciniphila (±4.5 log increase over two days), far exceeding the response of other bacteria present, together with an increase in propionate. These findings suggest that colonisation and mucin degradation by A. muciniphila is dependent on pH and the concentration of mucin. Our results revealed the preference of A. muciniphila for the distal colon environment due to its higher pH and uncovered the quick and stable response of A. muciniphila to mucin supplementation.