%Diets rich in fat compromise the immune system%

A UC Riverside study that could motivate your New Year's resolutions shows that the high-fat diets they affect genes linked not only to obesity, colon cancer and irritable bowel, but also the immune system, brain function and potential risk of COVID-19.

The results of research on high-fat diets were published in Scientific Reports.

High-fat diets: here's why it's not just an aesthetic problem

While other studies have examined the effects of high-fat diets, this one is unusual in its scope. The UCR researchers fed mice three different diets over the course of 24 weeks, in which at least 40 percent of the calories came from fat. Then, they looked not only at the microbiome, but also at genetic changes in all four parts of the gut.

One group of mice ate a diet of saturated fats from coconut oil, another ate modified monounsaturated soybean oil, and a third ate unmodified soybean oil rich in polyunsaturated fats. Compared to a low-fat control diet, all three groups experienced changes in gene expression, the process that turns genetic information into a functional product, such as a protein.

“There's a saying that plant-based diets are better for you, and in many cases that's true. However, high-fat diets, even plant-based fats, are cases where that's simply not true,” said Frances Sladek, a UCR professor of cell biology and senior author of the new study.

Some of the gut changes didn't surprise researchers, such as large changes in genes related to fat metabolism and the composition of gut bacteria. For example, they observed an increase in E. coli pathogen and a suppression of Bacteroides, which help protect the body from pathogens, in people who follow high-fat diets.

Other observations were more surprising, such as changes in genes that regulate susceptibility to infectious diseases. “We've seen pattern recognition genes, the ones that recognize infectious bacteria, take a hit. We saw cytokine signaling genes take a hit, which help the body control inflammation,” Sladek said.

“So it's a double problem. These high-fat diets compromise the host's immune system genes and also create an environment in which harmful gut bacteria can thrive.”

The team's previous work with soybean oil documents its link to obesity and diabetes, both major risk factors for COVID. This paper now shows that all three high-fat diets increase the expression of ACE2 and other host proteins that are used by COVID spike proteins to enter the body.

Additionally, the team observed that high-fat diets increased signs of stem cells in the colon. “You would think that would be a good thing, but they can actually be precursors to cancer,” Sladek said.

In terms of effects on gene expression, coconut oil showed the most changes, followed by unmodified soybean oil. The differences between the two soybean oils suggest that polyunsaturated fatty acids present in unmodified soybean oil, primarily linoleic acid, play a role in altering gene expression.

The negative changes in the microbiome in this high-fat diet study were more pronounced in mice fed the soybean oil diet. This is not surprising, as the same research team had previously documented other negative health effects from high soybean oil consumption.

In 2015, the team found that soybean oil induced obesity, diabetes, insulin resistance and fatty liver in mice. In 2020, the team of researchers showed that the oil could also affect brain genes linked to conditions such as autism, Alzheimer's disease, anxiety and depression.

Interestingly, in their current work they also found that the expression of several neurotransmitter genes was changed by high-fat diets, reinforcing the notion of a gut-brain axis that can be influenced by diet.

The researchers noted that these findings apply only to soybean oil and not to other soy products, tofu, or soy itself. “There are some really good things about soybeans. But too much oil is not good,” said UCR microbiologist Poonamjot Deol, who was co-first author of the current study along with UCR postdoctoral researcher Jose Martinez-Lomeli.

Additionally, the studies were conducted using mice, and mouse studies do not always translate to the same results in humans. However, humans and mice share 97.5% of their functioning DNA. Therefore, the findings are concerning, as soybean oil is the most commonly consumed oil in the United States and is increasingly used in other countries, including Brazil, China, and India.

By some estimates, Americans tend to get nearly 40 percent of their calories from fat, which mirrors what the mice were fed in this study. “Some fat is needed in the diet, perhaps 10 to 15%. However, most people, at least in this country, get at least three times the amount they need,” Deol said.

Readers shouldn't panic over a single meal. It is the long-term high-fat habit that has caused the observed changes. Recall that the mice were fed these diets for 24 weeks. “In human terms, it's like starting in childhood and continuing into middle age. A night's indulgence is not what these mice ate. It's more like a lifetime of food,” Deol said.

That said, the researchers hope the study will cause people to take a closer look at their eating habits.

Some people think, 'Oh, I'll just practice more and I'll be fine.' But eating this way regularly could impact the immune system and brain functioning,” Deol said. “You may not be able to simply eliminate these effects.”