# Microbiome-Mitochondrial Interactions Driving Cancer-Induced Cachexia in the Obese State

> **NIH NIH F99** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2024 · $40,199

## Abstract

PROJECT SUMMARY
Research: At the time of cancer diagnosis, 40% - 60% of patients are overweight or obese. Despite this, there
is a dearth of literature on the impact of weight status on cancer-induced cachexia - the unintentional loss of lean
mass, which directly contributes to functional dependency, poor treatment outcomes, and decreased survival.
An “obesity paradox” has been postulated; however, the epidemiology remains equivocal on the
benefits/detriments of obesity on cachexia status. While obesity and cachexia are diseases at opposite ends of
the weight spectrum, these pathologies share some underlying perturbations (e.g. mitochondrial dysfunction and
microbial dysbiosis) that may exacerbate functional decrements when these morbidities co-occur. Evidence
supports a role for mitochondrial dysfunction in the progression of cachexia. Indeed, we and others have shown
that impaired mitochondrial function and dysregulated mitochondrial quality control (biogenesis, dynamics, and
mitophagy) are associated with cachexia. Further, evidence links specific metabolites, microbes, and their
metabolic pathways with cachexia status. Incidentally, obesity is also associated with mitochondrial dysfunction
and alterations in gut bacterial populations. However, the impact of obesity on cachexia and associated
perturbations (mitochondrial dysfunction and gut dysbiosis) has not been established. Therefore, the goal of my
F99/K00 is to 1) understand the microbial and metabolic perturbations associated with cancer cachexia in the
obese state (F99), and 2) using multi-omics, examine the relationship between microbes and mitochondria in
cancer cachexia and identify strategies for intervention. My central hypothesis is that cancer-induced
cachexia is exacerbated in an obese state and gut microbial-muscle mitochondria interactions are
central in the coordination of this worsened phenotype. I will test this hypothesis in two specific aims as
follows: 1) Examine the impact of obesity on microbial alterations, metabolic perturbations, and skeletal muscle
dysfunction with cancer-induced cachexia in the obese state and 2) Establish microbiome-mitochondria
interactions in cancer cachexia in the context of obesity and identify strategies for intervention. These studies
will uncover the impact of obesity on cancer cachexia and will identify microbiome-mitochondrial interactions,
provoking novel opportunities for intervention. Career Goals: My long-term research goal is to become an
independent researcher at a top-tier research institution focused on prevention/treatment of cancer and cancer
therapy related off-target effects including cachexia. Career Development Plan: The proposed career
development plan is designed to enhance my knowledge, technical expertise, and professional skills.
Specifically, I will receive training in 1) obesity phenotyping and cachexia modeling, 2) mitochondrial behavior,
3) microbiome and microbial metabolites, and 4) professional development. The ...

## Key facts

- **NIH application ID:** 10990267
- **Project number:** 1F99CA294251-01
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** Thomas Cardaci
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $40,199
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10990267

## Citation

> US National Institutes of Health, RePORTER application 10990267, Microbiome-Mitochondrial Interactions Driving Cancer-Induced Cachexia in the Obese State (1F99CA294251-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10990267. Licensed CC0.

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