# Elaidic acid suppresses hepatocellular carcinoma growth through modulating the production of intestinal Ligilactobacillus murinus-derived spermidine

## TL;DR

Elaidic acid, a type of trans fatty acid, suppresses liver cancer growth by boosting a gut bacteria that produces a compound called spermidine.

## Contribution

This study reveals that elaidic acid reduces hepatocellular carcinoma by modulating gut microbiota to increase spermidine production.

## Key findings

- Elaidic acid levels are significantly lower in HCC patients compared to healthy individuals.
- Elaidic acid reduces HCC tumor growth in mice by increasing Ligilactobacillus murinus abundance.
- L. murinus-derived spermidine suppresses HCC growth and affects apoptosis-related biomarkers.

## Abstract

Dietary intervention provides a novel approach for cancer therapy. Elaidic acid (EA), which accounts for 80-90% of total trans fatty acids in foods, has recently been found to exert anti-tumor effects. However, the biological functions and underlying mechanisms of EA remain elusive in hepatocellular carcinoma (HCC). In this study, targeted fatty acid metabolomics demonstrated that among 44 types of fatty acids, the concentration of EA decreased most significantly when comparing plasma from HCC patients with plasma from healthy people. Through in vivo assays using HCC orthotopic and xenograft mouse models, we further revealed that dietary EA attenuates HCC growth. Notably, when gut microbiota was depleted using a cocktail of antibiotics, the anti-tumor effect of EA was diminished, confirming that EA suppresses HCC tumor growth by modulating gut microbiota. Mechanistically, analysis of 16S ribosomal RNA sequencing showed that dietary EA markedly increases the abundance of intestinal Ligilactobacillus murinus (L. murinus). Subsequent untargeted metabolomic sequencing analysis further demonstrated that dietary EA drives the production of L. murinus-derived spermidine (SPD), which attenuates HCC growth in vitro as well as in vivo. The observed impact correlated with the phosphorylation of p38 MAPK and the upregulation of biomarkers pertinent to apoptosis and proliferation, including tumor protein 53, bcl-2-associated X protein, and cysteine-requiring aspartate protease 3. Taken together, our findings highlight the important role of intestinal L. murinus-derived SPD in EA-mediated HCC suppression, thereby offering a promising dietary strategy for HCC treatment.