Aims: The molecular cross-talk between commensal bacteria and the gut playan important role in the maintenance of the intestinal homeostasis and generalhealth. Here, we studied the impact of a major Gram-positive anaerobicbacterium of the human gut microbiota, that is, Ruminococcus gnavus on theglycosylation pattern and the production of intestinal mucus by the goblet cells.Methods and Results: Our results showed that R. gnavus E1 specificallyincreases the expression and the glycosylation level of the intestinal glyco-conjugates by goblet cells in the colonic mucosa of mono-associated mice withR. gnavus E1 as well as in human HT29-MTX cells. Such an effect wasmediated through induction of the level of mRNA encoding for the majorintestinal gel-forming mucin such as MUC2 and various glycosyltransferaseenzymes.Conclusions: This study demonstrates for the first time that R. gnavus E1possess the ability to modulate the glycosylation profile of the glyco-conjugatemolecules and mucus in goblet cells.Significance and Impact of the Study: Furthermore, we demonstrated thatR. gnavus E1 modified specifically the glycosylation pattern and MUC2expression by means of a small soluble factor of peptidic nature (<3 kDa) andheat stable in the HT29-MTX cell.