The effects of dietary fat on gut microbial composition and function in ovarian cancer

TL;DR

This study shows that high-fat diets alter gut microbes and accelerate ovarian cancer growth in mice, suggesting diet affects cancer progression through gut bacteria.

Contribution

The study reveals novel connections between specific high-fat diets, gut microbial composition, and ovarian cancer tumor growth in a mouse model.

Findings

KD and HF/LC diets accelerated EOC tumor growth compared to LF/HC diets in mice.

HF/LC-fed mice had reduced gut microbiome diversity and higher abundance of Bacteroides and Enterococcus faecalis.

Metagenomic analysis showed HF/LC diets enriched polyamine biosynthesis and fatty acid oxidation pathways.

Abstract

The gut microbiome (GM) is pivotal in regulating inflammation, immune responses, and cancer progression. This study investigates the effects of a ketogenic diet (KD) and a high-fat/low-carbohydrate (HF/LC) diet on GM alterations and tumor growth in a syngeneic mouse model of high-grade serous ovarian cancer (EOC).

Thirty female C57BL/6J mice injected with KPCA cells were randomized into KD, HF/LC, and low-fat/high-carbohydrate (LF/HC) diet groups. Tumor growth was monitored with live, in vivo imaging. Stool samples were collected at the time of euthanasia and analyzed by 16SrRNA sequencing and shotgun metagenomic sequencing was performed to identify differential microbial taxonomic composition and metabolic function.

Our findings revealed that KD and HF/LC diets significantly accelerated EOC tumor growth compared to the LF/HC diet in a xenograft model. GM diversity was markedly reduced in KD and HF/LC-fed mice, correlating with increased tumor growth, whereas LF/HC-fed mice showed higher GM diversity. Metagenomic analyses identified distinct alterations in microbial taxa including Bacteroides, Lachnospiracae bacterium, Bacterium_D16_50, and Enterococcus faecalis predominantly abundant in HF/LC-fed mice, Dubsiella_newyorkensis predominantly abundant in LF/HC-fed, and KD fed mice showing a higher abundance of Akkermansiaand Bacteroides. Functional pathways across diet groups indicated polyamine biosynthesis and fatty acid oxidation pathways were enriched in HF/LC-fed mice.

These results highlight the intricate relationship between diet, the gut microbiome, and tumor metabolism. The potential role of dietary interventions in cancer prevention and treatment warrants further investigation.

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