PROJECT SUMMARY
A leading cause of obesity and diabetes is consumption of a Western-style diet rich in saturated fat and simple
sugars. Recent research shows that high fat (HF)-high sugar diets alter the microbial composition of the gut.
Interestingly, we previously showed that HF diets have a strong impact on the small bowel microbiota specifically
in the jejunum, the major site of nutrient digestion and absorption. Moreover, jejunal HF microbes increased lipid
absorption in adult germ-free mice compared to low fat (LF) diet microbes collected from the jejunum. However,
in this study, we focused on the bacterial taxa as opposed to fungal taxa. A critical gap exists in the literature
regarding the role of fungi in regulating the absorptive capacity of the gut in response to HF diets. Our long-term
goal is to elucidate the mechanisms by which candidate fungi such as Candida regulate lipid absorption, fat
transport and adiposity. The objective of this application is to determine the impact of Candida, in yeast or
hyphal form, on lipid digestive and absorptive capacity and obesity development. In addition, we will examine
the localization of Candida along the length of the gut. Our preliminary data demonstrate that C. albicans in yeast
and hyphal form triggers the upregulation of genes involved in fat absorption. Weekly supplementation of heat-
killed C. albicans also increased body weight gain in mice fed a HF diet and induced fatty acid translocase (Cd36)
expression in the jejunum. As emerging evidence suggests that diet-gut microbe interactions have the potential
to promote disease, we developed our central hypothesis that the gut mycobiota contributes to lipid absorptive
and digestive capacity in the small intestine. Two specific aims are proposed to test this hypothesis: Aim 1)
Test the localization and morphology of C. albicans and impact on host lipid uptake and obesity, Aim 2)
Determine the molecular mechanisms involved in C. albicans-mediated lipid absorption. We have only
reached the precipice of understanding how bacteria regulate nutrient digestion and absorption and even less is
known regarding the role of intestinal fungi. The proposed research is innovative and significant because it
will better define the small intestinal mycobiota, regional localization of Candida and better define the
mechanisms of host-microbe interactions that regulate absorption contributing to the development of obesity.