# Impact of the gut microbiome and diet on change in insulin homeostasis and cardiometabolic risk

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2021 · $541,829

## Abstract

PROJECT SUMMARY
Failure to increase insulin secretion and reduce insulin clearance to overcome tissue insulin resistance leads to
the development of type 2 diabetes (T2D). Components of the insulin axis (insulin sensitivity, insulin secretion,
insulin clearance) are critical to the genesis of T2D, yet the factors that account for their dysfunction and their
interactions with other factors are not understood. The nutritional components of diet pass through the
intestinal barrier in a complex interaction with the gut microbiota (the microbiome) to impact glucose
homeostasis. Our hypothesis is that change in three insulin axis traits is associated with gut microbial
composition and function, and this association is modified by dietary components (e.g., whole grains, red meat)
including systemic short chain fatty acids produced by the gut microbiota. This study will assess the insulin
axis, the gut microbiota and diet in a cohort of 500 non-diabetic adults (half African American, half non-
Hispanic White) over 2.5 years (sampled at three time points). Specific Aim 1 will administer, at each clinic
visit, a 75-g oral glucose challenge with 0, 30, 60, 120 min measurements (of insulin, glucose, and C-peptide)
to determine insulin sensitivity, secretion, and clearance; habitual diet will be determined by use of a validated
Food Frequency Questionnaire. Specific Aim 2 will characterize the gut microbiome for each participant by
performing 16S rDNA sequencing and low-pass metagenomic sequencing on stool samples collected at all
three visits. Together, these data will test the hypothesis that increased insulin resistance, impaired insulin
secretion, and decreased insulin clearance (all diabetogenic changes) developing over time are associated
with a reduced (at baseline) or declining (over time) abundance of short chain fatty acid-producing bacteria in
the gut, in part attributable to unhealthy dietary patterns. Specific Aim 3 will utilize samples collected at the
three time points to probe the functional profile of the gut microbiome by conducting deep metagenomic
sequencing and assessment of circulating short chain fatty acid levels in a subset of 180 individuals with
extreme changes (increase and decrease) versus those with no change in insulin axis traits, thereby identifying
microbial functions that underlie change versus stability in insulin axis traits. This study has high impact,
yielding knowledge that can lead to novel microbiome-based diagnostics, prevention, and/or treatment
measures (e.g., specific diets; antibiotic or probiotic treatment) to reduce the public health burden of T2D.

## Key facts

- **NIH application ID:** 10126831
- **Project number:** 5R01DK109588-05
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Mark Goodarzi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $541,829
- **Award type:** 5
- **Project period:** 2017-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126831

## Citation

> US National Institutes of Health, RePORTER application 10126831, Impact of the gut microbiome and diet on change in insulin homeostasis and cardiometabolic risk (5R01DK109588-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10126831. Licensed CC0.

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