Research News

Cleveland Clinic researchers have connected high-fat/low-carb diets – including ketogenic or “keto” diets – with gut microbiome imbalances and with increased tumor growth, severity and spread in preclinical models of ovarian cancer. The study did not show the same pattern with high carb/low-fat diets.  

Published in the Journal of Ovarian Research, the study describes a new pathway for how diet can influence cancer outcomes through the bacteria that live in our gut.  

“Patients often ask me about what diet they should follow during treatment,” says gynecologic oncologist and study co-lead author Mariam AlHilli, MD. “We know that diet quality is a risk factor for some cancers, including ovarian cancer. But the mechanisms are still not clearly understood.” 

Ketogenic diets are medically prescribed for some conditions but not widely used in cancer care. Dr. AlHilli first observed that ketogenic diets promoted tumor growth in preclinical ovarian cancer models in 2023. She and co-lead author, Microbial Sequencing & Analytics Core Director Naseer Sangwan, PhD, then set out to find whether the gut microbiome could explain the deadly outcomes. 

“Diet can influence the growth and proliferation patterns of key microorganisms colonizing various sections of the human intestine,” Dr. Sangwan explains. “These microbes ultimately produce biomolecules such as metabolites that can affect the growth patterns of human cancer stem cells. We wanted to see if that’s what was happening here.” 

Dr. Sangwan’s team analyzed the microbiome composition of ovarian cancer in preclinical models. They also looked at what these bacteria were doing to identify activity that might promote or prevent tumor growth. They found that high-fat/low-carb diets depleted helpful bacteria that prevent tumors, and enriched microbes associated with fucose metabolism, polyamine biosynthesis and fatty acid oxidation. All three bacterial activities can increase inflammation and promote tumor growth. 

Testing the opposite diet plan, low-fat/high-carb, shifted the microbiome towards microbial communities that produced short-chain fatty acids, which reduce inflammation and suppress tumors. 

Dr. AlHilli warns that while the microbial shifts and behaviors her team saw in this study are usually associated with tumor growth, more research is needed to make sure the bacteria directly drive cancer progression in this context. 

“Ovarian cancer is highly reliant on lipid metabolism, so our findings highlight a potential link between high-fat diets and tumor progression,” Dr. AlHilli says. “More research is needed to confirm cause-and-effect, but these findings give us an excellent place to start.” 

While ketogenic diets for cancer have shown promise in some cases, studies like Drs. AlHilli and Sangwan’s reinforce that nutrition plans need to be tailored to the cancer type and individual patient. Cleveland Clinic researchers are actively exploring this across multiple tumor types, including prostate cancer. 

“Clinical recommendations can’t be made based on our data yet,” Dr. AlHilli emphasizes. “But future trials, like those exploring low-fat/high-carb, intermittent fasting or fasting-mimicking diets, may offer more insights. In a perfect world, we’d be able to tailor diets to each patient’s tumor biology and microbiome. That’s the future we’re working toward.”