Prebiotic oligofructose protects against high-fat diet-induced obesity by changing the gut microbiota, intestinal mucus production, glycosylation and secretion

Obesity is a major risk factor for the development of type 2 diabetes and cardiovascular diseases, and gut microbiota plays a key role in influencing the host energy homeostasis. Moreover, obese mice have a different gut microbiota composition, associated with an alteration of the intestinal mucus layer, which represents the interface between the bacteria and the host. We previously demonstrated that prebiotic treatment with oligofructose (FOS) counteracted the effects of diet-induced obesity, together with changes in the gut microbiota composition, but it is not known if the intestinal mucus layer could be involved. In this study, we found that, in addition to preventing high-fat diet (HFD) induced obesity in mice, the treatment with FOS increased the expression of numerous genes involved in mucus production, glycosylation and secretion, the expression of both secreted and transmembrane mucins, and the differentiation and number of goblet cells. These results were associated with significant changes in the gut microbiota composition, with FOS significantly increasing the relative and absolute abundance of the bacterial genera <i>Odoribacter, Akkermansia</i>, two unknown <i>Muribaculaceae</i> and an unknown <i>Ruminococcaceae</i>. Interestingly, all these bacterial genera had a negative association with metabolic parameters and a positive association with markers of the mucus layer. Our study shows that FOS treatment is able to prevent HFD-induced metabolic disorders, at least in part, by acting on all the processes of the mucus production. These data suggest that targeting the mucus and the gut microbiota by using prebiotics could help to prevent or mitigate obesity and related disorders.