When feeling stressed, many people turn to comfort foods high in fat and sugar. However, a recent study from the University of Colorado Boulder suggests that this coping mechanism may be counterproductive. Published in the journal Biological researchThe study found that in animals, a high-fat diet can disrupt gut bacteria, alter behavior and affect brain chemicals in ways that promote anxiety.
The motivation for this study comes from the growing recognition of the gut-brain axis, a complex communication network linking the digestive tract and the brain. Researchers are increasingly interested in how this connection influences mental health, particularly through the gut microbiome, which is made up of trillions of bacteria living in our intestines. Previous research has shown that the composition of gut bacteria can significantly affect physical and mental health, including diseases like obesity, anxiety, and depression.
Given that obesity and anxiety disorders are common and increasing in prevalence, the researchers sought to determine whether diet could be a common factor influencing both conditions. Specifically, they wanted to determine whether a high-fat diet, common in many modern diets, could alter the gut microbiome in ways that impact brain function and behavior. Understanding these mechanisms could provide insights into how food choices affect mental health and potentially offer new avenues for treatment and prevention.
To explore these questions, the researchers conducted a controlled experiment on adolescent rats, chosen because their developmental stage is analogous to that of human adolescents, a critical period for establishing long-term dietary and health patterns.
The rats were divided into two groups. The first group was fed a standard diet containing about 11% fat, while the other group was fed a high-fat diet containing 45% fat, mostly saturated animal fat. The duration of the dietary intervention was nine weeks, a significant portion of the rats’ lifespan, or several years in human terms.
Throughout the study, the researchers collected stool samples weekly from both groups of rats to monitor changes in their gut microbiota. These samples were analyzed to assess the diversity and composition of gut bacteria, focusing on the balance between Firmicutes and Bacteroidetes, two major bacterial groups known to be influenced by diet and associated with health problems.
After nine weeks on the diet, the rats underwent a series of behavioral tests designed to measure anxiety-like behavior. These tests included the elevated plus maze, which assesses anxiety based on rats’ willingness to explore the open, elevated arms of a maze, and other tests that measure responses to stress and new environments. The researchers also examined the rats’ brains to measure the expression of specific genes involved in serotonin production and signaling.
The main finding was that rats fed a high-fat diet had significantly different gut microbiota profiles than those fed a standard diet. Specifically, the high-fat diet led to a decrease in gut bacterial diversity, which is generally associated with poorer health outcomes. The high-fat diet group showed a higher ratio of Firmicutes to Bacteroidetes, an imbalance often linked to obesity and metabolic disorders.
Behavioral assessments revealed that rats fed a high-fat diet exhibited more anxiety-like behaviors than their counterparts fed a standard diet. This was particularly evident in tests such as the elevated plus maze, where rats fed a high-fat diet were less willing to explore open, elevated spaces, indicating higher levels of anxiety. These behavioral changes suggest that alterations in the gut microbiota due to the high-fat diet had a direct impact on the rats’ anxiety-related responses.
“Everyone knows these foods are not healthy, but we tend to think of them as just a little weight gain,” said the study’s lead author, Christopher Lowry, a professor of integrative physiology at the University of Colorado Boulder. “If you understand that they also impact your brain in ways that can promote anxiety, the stakes are even higher.”
At the molecular level, the study found that the high-fat diet affected the expression of specific genes involved in the production and signaling of serotonin in the brain. The high-fat diet group showed increased expression of genes such as tph2, htr1a, and slc6a4 in the dorsal raphe nucleus of the brainstem. These genes are involved in the synthesis and signaling of serotonin, a neurotransmitter often associated with feelings of well-being and happiness. However, the increased expression of these genes may also be linked to anxiety, suggesting that the high-fat diet created a chemical environment in the brain that was conducive to anxiety.
“To think that a high-fat diet could change the expression of these genes in the brain is extraordinary,” Lowry said. “The high-fat group essentially had the molecular signature of high anxiety in their brains.”
The researchers hypothesize that disruption of the gut microbiota could compromise the intestinal wall, allowing bacteria and their metabolites to enter the bloodstream and interact with the brain via the vagus nerve. This gut-brain communication pathway could influence brain function and contribute to the observed anxiety-like behaviors. The results indicate that the high-fat diet not only affected physical health, as evidenced by weight gain and changes in gut bacteria, but also had profound effects on mental health by altering brain chemistry.
The study has limitations, including that it is based on an animal model, which does not fully replicate human physiology and behavior. Future research should aim to confirm these findings in human subjects, explore the specific mechanisms of gut-brain communication, and examine the impact of different types of dietary fat.
“Given the early introduction of high-fat foods into children’s diets and the ever-increasing obesity epidemic, our data open up a possible scenario that dietary choices during adolescence may influence the gut microbiome, brainstem serotonergic systems, and susceptibility to the development of psychiatric disorders in adulthood. This knowledge could lead to novel microbiome-based approaches to prevent stress-related psychiatric disorders such as anxiety disorders,” the researchers conclude.
The study, titled “High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats,” was authored by Sylvana I. S. Rendeiro de Noronha, Lauro Angelo Gonçalves de Moraes, James E. Hassell Jr., Christopher E. Stamper, Mathew R. Arnold, Jared D. Heinze, Christine L. Foxx, Margaret M. Lieb, Kristin E. Cler, Bree L. Karns, Sophia Jaekel, Kelsey M. Loupy, Fernanda C. S. Silva, Deoclécio Alves Chianca-Jr., Christopher A. Lowry, and Rodrigo Cunha de Menezes.