Aug. 2, 2023 -- A popular ingredient in the American diet has been linked to ulcerative colitis, a type of inflammatory bowel disease marked by a chronically inflamed large intestine. The ingredient is soybean oil, which is very common in processed foods. In fact, U.S. per capita consumption of soybean oil increased more than 1,000-fold during the 20th century.
In a study from the University of California Riverside and UC Davis, mice fed a diet high in soybean oil were more at risk of developing colitis.
The likely culprit? Linoleic acid, an omega-6 fatty acid that comprises up to 60% of soybean oil.
Small amounts of linoleic acid help maintain the body’s water balance. But Americans derive as much as 10% of their daily energy from linoleic acid, when they need only 1% to 2%, the researchers say.
The findings build on earlier research linking a high-linoleic acid diet with inflammatory bowel disease, or IBD, in humans. (Previous research in mice has also linked high consumption of the oil with obesity and diabetes in the rodents.)
For the new study, the researchers wanted to drill down into how linoleic acid affects the gut.
How Linoleic Acid May Promote Inflammation
In mice, the soybean oil diet upset the ratio of omega-3 to omega-6 fatty acids in the gut. This led to a decrease in endocannabinoids, lipid-based molecules that help block inflammation.
Enzymes that metabolize fatty acids are “shared between two pathways,” said study co-author Frances Sladek, PhD, professor of cell biology at UC Riverside. “If you swamp the system with linoleic acid, you’ll have less enzymes available to metabolize omega-3s into good endocannabinoids.”
The endocannabinoid system has been linked to “visceral pain” in the gut, said Punyanganie de Silva, MD, MPH, an assistant professor at Brigham & Women's Hospital, who was not involved in the study. But the relationship between the endocannabinoid system and inflammation has yet to be fully explored.
“This is one of the first papers that has looked at the association between linoleic acid and the endocannabinoid system,” de Silva said. “[The researchers] propose a potential new mechanism of how linoleic acid may increase inflammation” -- that is, through its impact on the endocannabinoid system.
Changes in the Gut Microbiome
The gut microbiome of the mice also showed increased amounts of adherent invasive E. coli, a type of bacteria that grows by using linoleic acid as a carbon source. A “very close relative” of this bacteria has been linked to IBD in humans, Sladek said.
Using a method known as metabolomics, the researchers studied 3,000 metabolites in both the intestinal cells of the mice and the bacteria. Endocannabinoids decreased in both.
“We were actually quite surprised. I didn't realize that bacteria made endocannabinoids,” Sladek said.
Helpful bacteria, such as the probiotic lactobacillus species, died off. The mice also had increased levels of oxylipins, which are correlated with obesity in mice and colitis in humans.
A High-Linoleic Acid Diet Could Mean a Leaky Gut
Linoleic acid binds to a protein known as HNF-4α. Disrupting the expression of this protein can weaken the intestinal barrier, letting toxins flow into the body -- more commonly known as leaky gut. Mice on the soybean oil diet had decreased levels of the protein and more porous intestinal barriers, raising the risk for inflammation and colitis.
“The HNF-4α protein is conserved from mouse to human, so whatever's happening to it in the context of the mouse gut, there's a very high chance that a similar effect could be seen in humans as well,” said study co-author Poonamjot Deol, PhD, an assistant professional researcher at UC Riverside.
Still, de Silva urges “some caution when interpreting these results,” given that “this is still experimental and needs to be reproduced in clinical studies as humans have a far more varied microbiome and more variable environmental exposures than these very controlled mouse model studies.”
De Silva says cooking with olive oil can "help increase omega-3: omega-6 ratios" and advises eating a varied diet that includes omega-3 fats, such as flaxseed and walnuts, and minimal amounts of processed foods and saturated fats.
Looking ahead, endocannabinoids are being explored as “a potential therapy for treating IBD symptoms,” said Deol. She hopes to delve further into how linoleic acid affects the endocannabinoid system.