# Metabolomics of symptomatic gallstone disease in COMETS

> **NIH NIH R03** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $126,000

## Abstract

PROJECT SUMMARY/ ABSTRACT
In this proposed R03 application, we will investigate plasma metabolomics and its interaction with the gut
metabolome and metagenome in relation to risk of symptomatic gallstone disease. Gallstone disease is the
leading cause for gastrointestinal-related hospital admissions in the U.S., with an annual economic burden of
6.5 billion dollars and accounts for about 2% of the US federal health budget. Our overarching hypothesis is that
plasma metabolomic signatures that capture symptomatic GSD risk may be influenced by gut microbes through
alterations in deconjugation of primary bile acids, synthesis of secondary bile acids, and by affecting
enterohepatic circulation of molecules in bile acid and cholesterol metabolism pathways. The applicant has
recently led a study to identify plasma metabolomic markers of gallstone disease in three large prospective US-
based cohorts, as part of his K01 project, “Risk prediction of symptomatic gallbladder disease.” In Aim 1 of this
R03 proposal, we plan to continue this work on gallbladder disease within the NIH-led large COnsortium of
METabolomics Studies (COMETS) to (i) replicate recently identified metabolomics-based biomarkers of
symptomatic gallstone disease in diverse populations, (ii) to utilize the larger sample sizes in COMETS to identify
novel plasma metabolomic signatures of symptomatic gallstone disease. This project aligns with the applicant’s
long-term goal to use ‘omics approaches to understand the etiological underpinnings of symptomatic gallstone
disease and to develop genomic and metabolomics-based biomarker tools to improve risk prediction of
symptomatic gallstone disease. Emerging evidence also suggests that the gut microbiome may play a critical
role in maintaining the diversity of bile acids, and the composition of bile. Therefore, in Aim 2 of this application,
we propose to conduct a pilot study in participants from Massachusetts General Hospital to investigate the role
of gut-microbial communities in the risk of symptomatic gallstone disease and to determine whether this is
mediated through their influence on the plasma metabolome. The expected outcome of this proposed R03
application and the ongoing K01 research is the comprehensive metabolomic profiling of symptomatic gallstone
disease in distinct populations, accurate risk prediction of symptomatic gallstone disease, and the examination
of a link between plasma metabolomics and the gut microbiome in gallstone disease risk. The successful
accomplishment of project aims will help generation of preliminary data to position the applicant for future R01
studies that can provide proof-of-principle of the potential of exploiting metabolomics for precision medicine-
based risk stratification for clinical interventions, a high NIDDK research priority.

## Key facts

- **NIH application ID:** 10358593
- **Project number:** 5R03DK127148-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Amit Dolar Joshi
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $126,000
- **Award type:** 5
- **Project period:** 2021-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10358593

## Citation

> US National Institutes of Health, RePORTER application 10358593, Metabolomics of symptomatic gallstone disease in COMETS (5R03DK127148-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10358593. Licensed CC0.

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