Carotenoids: a missing link between Gut Microbiota and Obesity
Abdulkerim Eroglu FASEB J 2021 35(S1) 04313
Carotenoids are naturally occurring red, orange, and yellow pigments found mainly in fruits and vegetables. They may function as vitamin A precursors, have important antioxidant, immunological or metabolic functions. The overall absorption efficiency of carotenoids from whole foods is considerably lower in the small intestine. When carotenoids enter the colon together with indigestible dietary compounds, they can become a potential substrate for microbial fermentation. Carotenoids can be further released, or additional conversions can happen within colon epithelial cells.
This study's overall objective is to determine the impact of carotenoids on obesity-associated gut dysfunction (microbial dysbiosis, impaired intestinal barrier function, and low-grade inflammation). Our central hypothesis is that carotenoids escaping the absorption in the small intestine can be transformed by the gut microbiota in the colon. First, we examined the molecular mechanisms behind the anti-inflammatory action of one of the major dietary carotenoid, β-carotene (BC), and its role in maintaining gut barrier integrity using in vitro intestinal epithelial cell model. We found out that BC could improve colonic inflammation by blocking inflammatory transcription factors and subsequently reducing pro-inflammatory cytokines in the colon. We have also seen that BC could improve gut barrier integrity within colon epithelial cells when cells challenged with endotoxins.
Next, we determined the impact of microbial metabolism and fermentation on the carotenoids present in the colon using an ex vivo fecal fermentation model. We demonstrated that BC would be metabolized by the microbiome in human stool samples. Finally, we plan to examine the effect of carotenoid-rich diet on obesity-associated gut dysfunction, metabolic endotoxemia, and gut barrier in vivo using a murine model. We will characterize carotenoid-induced changes in the gut microbiota utilizing shotgun sequencing and multi-omic approaches, including metabolomics and shotgun metagenomics in the diet-induced obesity animal model.
