# Interplay between Dietary Fiber and Gut Microbiota in Hepatocellular Carcinoma

> **NIH NIH R01** · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · 2021 · $59,333

## Abstract

Project Summary
The overall goal of our research is to identify the mechanisms and factors/metabolite(s)
by which dietary soluble fiber inulin induces hepatocellular carcinoma (HCC) in mice
lacking toll-like receptor 5 (TLR5). TLR5, an innate immune receptor that senses
bacterial flagellin, plays a critical role in gut microbiota homeostasis. Accordingly, TLR5
deficient mice display hallmarks of metabolic syndrome, which is absolutely microbiota
dependent. This work aims to elucidate how a natural dietary component and widely
used food additive drives HCC in innate immune deficient mice coupled with gut
microbiotal overgrowth. Three specific aims are proposed, each of which investigates
the mechanisms by which HCC develops in mice with gut dysbiosis. The three aims are
interrelated, independently achievable and address the contributions of (i) structurally
different natural soluble fibers, (ii) gut microbiota, and (iii) host hepatic
lipogenesis/lipolysis to the development of HCC.
This proposal has potential implications for public health, given the prevalent and
overuse of inulin in the food industry. Our work would elucidate the underappreciated
potential detrimental effects of inulin and/or SCFAs. Further, human HCC is the sixth
most common cancer and third most cause of cancer related deaths globally. The higher
mortality rates in patients with HCC are due to poor and late stage diagnosis because of
its heterogeneous and asymptomatic nature. This warrants a novel, hepatocarcinogen
independent model to better understand human HCC. This proposal seeks to fulfill this
constraint.

## Key facts

- **NIH application ID:** 10411391
- **Project number:** 3R01CA219144-06S1
- **Recipient organization:** UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
- **Principal Investigator:** MATAM VIJAY-KUMAR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $59,333
- **Award type:** 3
- **Project period:** 2017-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10411391

## Citation

> US National Institutes of Health, RePORTER application 10411391, Interplay between Dietary Fiber and Gut Microbiota in Hepatocellular Carcinoma (3R01CA219144-06S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10411391. Licensed CC0.

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