# Microbial drivers of metabolically unhealthy obese phenotype

> **NIH NIH K01** · WASHINGTON UNIVERSITY · 2024 · $152,388

## Abstract

PROJECT SUMMARY
This application for the Mentored Research Scientist Development Award will facilitate the principal investigator
(PI)’s transition to independence dissecting host-microbe interactions in obesity-related metabolic diseases.
Candidate: The PI is an experimental biologist with a strong background in gut mucosal immunology and
infection biology. She did her postdoctoral training under the mentorship of Dr. Rodney Newberry, a mucosal
immunology expert. Under Dr. Newberry’s guidance, the PI demonstrated the novel role of intestinal goblet cells
in promoting immune tolerance to luminal antigens. Additionally, the PI has also demonstrated how enteric
bacteria interact with intestinal goblet cells to modulate their function. She will leverage the skills gained during
her training to characterize the dialogue between obesity-associated gut microbes and intestinal immune cells.
Career Development Plan: The PI will execute this proposal under the co-mentorship of Dr. Newberry and Dr.
Samuel Klein (a leader in the field of obesity research), advised by a team of scientific experts who also have
experience in nurturing independent investigators. Washington University provides an outstanding environment,
collaborators and cores that will foster the PI’s career development. This proposal builds on the PI’s prior
experience and fills in the gaps in her training, providing her with the tools needed for independence. It includes
the following objectives: (1) master techniques in macrophage biology (i.e., immune cell trafficking, phenotyping);
(2) developing expertise in obesity and metabolic dysfunction; (3) training in microbial ecology; (4) immersion in
bioinformatics; and (5) publishing manuscripts directly related to this proposal.
Research Plan: The scientific premise of the proposal is that gut microbiota from individuals with metabolically
unhealthy obesity (MUO) compared to metabolically healthy obesity (MHO) propel intestinal and adipose tissue
inflammation. To investigate the role of microbial drivers on the onset of metabolic syndrome, the PI has
established a model of colonizing genetically identical wildtype mice consuming a normal chow diet with stool
specimens collected from well-characterized obese or metabolically-healthy lean (MHL) human subjects with
known degrees of adipose tissue inflammation, glucose intolerance and whole-body insulin sensitivity.
Preliminary studies demonstrate that mice colonized with MUO, but not MHO or MHL donor microbiota have
glucose intolerance, higher serum insulin concentration and significant expansion of macrophages in the
intestine and adipose tissue. By completing the proposed aims, the PI will address 1) whether gut microbes from
people with MUO promote host inflammation and the onset of metabolic diseases, and 2) determine the
contribution of monocuclear phagocytes in microbiota driven-metabolic dysfunction. In completing these aims,
the PI will complement her expertise in mucosal immunology wit...

## Key facts

- **NIH application ID:** 10831509
- **Project number:** 5K01DK133670-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Devesha Kulkarni
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $152,388
- **Award type:** 5
- **Project period:** 2022-07-01 → 2024-08-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10831509

## Citation

> US National Institutes of Health, RePORTER application 10831509, Microbial drivers of metabolically unhealthy obese phenotype (5K01DK133670-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10831509. Licensed CC0.

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