# Investigating Metabolically Protective Members of the Microbiota that Modulate Ceramides

> **NIH NIH F30** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $53,974

## Abstract

Project Summary
The number of individuals with metabolic diseases like obesity and type 2 diabetes is growing at overwhelming
rates globally, increasingly affecting younger populations, and disproportionally affect under-served
communities. Emerging clinical, epidemiological, and laboratory research has demonstrated an essential role for
gut bacteria in the regulation of metabolism. Another key contributor to the pathogenesis of these metabolic
diseases are the sphingolipids ceramides. Ceramides are produced in response to increased fat intake and
mediate many of the molecular pathways that cause increased lipid uptake, insulin resistance, and fatty liver
disease. A few studies have begun to investigate the relationship between the gut microbiota, ceramides, and
metabolic diseases, and have shown that the microbiota can regulate ceramide production. Despite these
studies, it remains unclear which bacteria and how these bacteria impact ceramide production and ultimately
host metabolism. Our lab has identified a community of Clostridia Class bacteria that provide metabolic
protection from a high-fat diet in the form of decreased weight gain, improved leanness, and lower fasting
glucose. Furthermore, we have found that Clostridia reduce the rate of ceramide production.
The objective of this proposal is to understand which bacteria are essential to providing metabolic protection and
determine how these bacteria are impacting ceramide synthesis and overall host metabolism. We hypothesize
that select Clostridia bacteria can protect from features of metabolic disease through decreasing ceramides and
reducing lipid absorption in the gut epithelium. We will test this hypothesis in two aims: 1) defining the community
of Clostridia that protect from features of metabolic disease induced by a high-fat diet, and 2) determining if
Clostridia decrease ceramides and lipid absorption in the gut epithelium. Aim 1 will continue to culture, genetically
characterize, and define the most limited community of Clostridia that provides metabolic protection. Aim 2 will
use in vitro and in vivo approaches with germ-free (GF) and gnotobiotic mouse models to assess the relationship
between Clostridia and ceramides in the context of lipid absorption. This proposed work will have a significant
impact on the study of the metabolic disease and the microbiota by providing novel insight into microbiota-driven
mechanisms that can be leveraged for therapeutic benefit.

## Key facts

- **NIH application ID:** 10862789
- **Project number:** 5F30DK127846-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Kendra Alyse Klag
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 5
- **Project period:** 2021-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862789

## Citation

> US National Institutes of Health, RePORTER application 10862789, Investigating Metabolically Protective Members of the Microbiota that Modulate Ceramides (5F30DK127846-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10862789. Licensed CC0.

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