Mucin as a Functional Niche is a More Important Driver of in Vitro Gut Microbiota Composition and Functionality than Supplementation of Akkermansia m uciniphila.

IMPORTANCE SECTION Research into identification of biomarkers for gut health and ways to modulate the microbiota composition and activity to improve health, has put Akkermansia muciniphila in the spotlight. As a mucin degrader, A. muciniphila colonizes the interesting but not-fully described host-glycan degradation niche., . Plenty of research concerning A. muciniphila has been done, but little is known about its behavior in the complex microbial ecosystem in the colon, about the potential role of mucins to influence A. muciniphila behavior and the impact of its probiotic administration on the microbial ecosystem.This study aimed at investigating the impact of A. muciniphila administration on the endogenous community while also taking into account its nutritional specificity. As such, the effect of A.mucinihpila administration was investigated with and without addition of mucin. This allowed us to elucidate the importance of mucin presence to modulate the efficiency of the probiotic supplementation with A. muciniphila Akkermansia muciniphila is an abundantly present commensal mucin degrading gut bacterium (1 - 4%) , widely distributed among healthy individuals. It has been positioned as a health biomarker and is currently explored as a biotherapeutic agent and next generation probiotic. Preliminary and ongoing research is mostly based on in vivo mouse models and human intervention trials. While these allow the assessment of physiologically relevant endpoints, the analysis of fecal samples presents limitations with respect to the in-depth mechanistic characterization of Akkermansia effects at the level of the microbiome. We aimed to evaluate the effect of A. muciniphila treatment on the endogenous community from four different donors in a validated, controlled in vitro model of the gut microbial ecosystem (SHIME). Taking into account the nutritional specificity of A. muciniphila, and the prebiotic-like action of mucins in the colon environment, the interplay between mucin, A. muciniphila and the endogenous community was investigated. The effects on the microbial community composition and functionality of A. muciniphila supplementation without mucin were limited, whereas mucin addition successfully induced compositional and metabolic changes in the gut microbiota. Indeed, mucin addition resulted in significantly higher acetate, propionate and butyrate production for all four donors, and the increase of several species, including A. muciniphila, Ruminococcus, Clostridium cluster XIVa, and Lachnospiraceae This study revealed that the supplementation of A. muciniphila together with mucin limited the observed prebiotic-like effect of mucin in inducing compositional changes.