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The role of the gut mycobiota in regulating host lipid absorption and obesity

Award Number: R21DK129890
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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The role of the gut mycobiota in regulating host lipid absorption and obesity - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $141,408 )
2024	2024	MIDWESTERN UNIVERSITY	555 31ST ST	DOWNERS GROVE	IL	60515	DUPAGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	6/7/2024	NON-COMPETING CONTINUATION	$141,408
														Subtotal = $141,408

Issue Date FY: 2023 ( Subtotal = $158,559 )
2023	2023	MIDWESTERN UNIVERSITY	555 31ST ST	DOWNERS GROVE	IL	60515	DUPAGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/20/2023	NON-COMPETING CONTINUATION	$158,559
														Subtotal = $158,559

Issue Date FY: 2022 ( Subtotal = $165,252 )
2022	2022	MIDWESTERN UNIVERSITY	555 31ST ST	DOWNERS GROVE	IL	60515	DUPAGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	4/2/2022	NEW	$165,252
														Subtotal = $165,252

Grand Total All Awards = $465,219

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The role of the gut mycobiota in regulating host lipid absorption and obesity

Award Number: R21DK129890

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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