# Interplay between Dietary Fiber and Gut Microbiota in Hepatocellular Carcinoma

> **NIH NIH R01** · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · 2020 · $56,073

## Abstract

Parent R01 Abstract
The parental R01 grant discussed the novel interplay among dietary fermentable fibers, host gut
microbiota/metabolites, and host innate immunity in the progression of hepatocellular carcinoma
(HCC; most common liver malignancy). Natural dietary fibers consist of fermentable fibers that
are metabolized by the gut microbiota (GM) into short chain fatty acids (SCFAs) and insoluble
fibers that aid in roughage. In particular, SCFAs have been attributed to alleviating metabolic
syndrome (i.e. obesity), which has made dietary fermentable fibers (e.g. inulin, pectin) a target for
food industries. This includes making them commercially available as both a prebiotic and a
supplemental fiber source in processed foods. Based on this notion, we believed that
supplementing a fermentable fiber diet could alleviate the metabolic syndrome exhibited in Toll-
like receptor 5 deficient mice (Tlr5KO; innate immune receptor responsible in recognizing
bacterial flagellin and maintaining GM homeostasis). Upon feeding an inulin-containing diet (ICD)
diet, we observed that ~40% of Tlr5KO mice were protected from metabolic syndrome.
Alarmingly, however, this subset of Tlr5KO mice developed indices of cholestasis such as
hyperbilirubinemia and cholemia, which subsequently lead to the 100% guaranteed development
of multinodular HCC, characterized by hepatic ballooning/adipoma, within 6 months (Singh et al.,
Cell 2018). Histological analysis of the livers in hyperbilirubinemic (H-bili) Tlr5KO mice further
revealed hyperplasia, immune cell infiltration, necrosis and steatosis, which was absent in wild-
type (WT) and low bilirubin (L-bili) Tlr5KO mice. Interestingly, Tlr5KO mice maintained on a 100%
non-fermentable fiber diet (i.e. cellulose) were protected from HCC. To further determine the
influence of fermentable fibers on HCC development, in specific aim 1 we will employ alternative
fermentable fibers (i.e. guar guam, carrageenan) and monitor for HCC progression. Completion
of this aim will further support our hypothesis that the beneficial effects of dietary fermentable
fibers are contingent on the GM status of an organism. Alongside, due to the presence of hepatic
steatosis in susceptible Tlr5KO mice, we strive in specific aim 3 to determine the role of lipogenic
and lipolytic enzymes in the process of HCC development. In particular, we will target stearoyl-
CoA desaturase-1 (SCD1) and phospholipase D1 (PLD1), where we believe that deletion of either
enzyme will confer protection in Tlr5KO mice. Overall, completion of this proposal should not only
unravel the contributory role of fermentable fibers in HCC development, but also provide
therapeutic targets that can reduce the risk of liver cancer pathogenesis.

## Key facts

- **NIH application ID:** 10133382
- **Project number:** 3R01CA219144-05S1
- **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:** 2020
- **Award amount:** $56,073
- **Award type:** 3
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133382

## Citation

> US National Institutes of Health, RePORTER application 10133382, Interplay between Dietary Fiber and Gut Microbiota in Hepatocellular Carcinoma (3R01CA219144-05S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10133382. Licensed CC0.

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