Scientists uncover “extraordinary” impact of high-fat diet on anxiety via gut-brain axis

When feeling stressed, many people reach for 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 Research, the 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 stems from the growing recognition of the gut-brain axis — a complex communication network linking the gastrointestinal tract and the brain. Researchers have become increasingly interested in how this connection influences mental health, particularly through the gut microbiome, which consists of trillions of bacteria living in our intestines. Previous research has shown that the composition of gut bacteria can significantly affect both physical and mental health, including conditions like obesity, anxiety, and depression.

Given that obesity and anxiety disorders frequently co-occur and are both rising in prevalence, the researchers aimed to explore whether diet could be a common factor influencing both conditions. Specifically, they wanted to investigate if a high-fat diet, which is common in many modern diets, could alter the gut microbiome in a way that impacts brain function and behavior. Understanding these mechanisms could provide insights into how dietary choices affect mental health and potentially offer new avenues for treatment and prevention.

To investigate these questions, the researchers conducted a controlled experiment using adolescent rats, chosen because their developmental stage is analogous to that of human teenagers, a critical period for establishing long-term dietary and health patterns.

The rats were divided into two groups. One group was fed a standard diet containing about 11% fat, while the other group received a high-fat diet with 45% fat, primarily from saturated animal fats. The duration of the dietary intervention was nine weeks, a significant portion of the rats’ lifespan, equivalent to several years in human terms.

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Throughout the study, the researchers collected fecal 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 the gut bacteria, focusing on the balance between Firmicutes and Bacteroidetes, two major bacterial groups known to be influenced by diet and associated with health outcomes.

After the nine-week dietary period, 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 the willingness of the rats to explore 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 primary discovery was that rats fed a high-fat diet exhibited significantly different gut microbiota profiles compared to those on 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 an increased ratio of Firmicutes to Bacteroidetes, a balance shift often linked to obesity and metabolic disorders.

The behavioral assessments revealed that rats on the high-fat diet exhibited more anxiety-like behaviors compared to their counterparts on the standard diet. This was particularly evident in tests like the elevated plus maze, where the high-fat diet rats were less willing to explore open, elevated spaces, indicating higher anxiety levels. These behavioral changes suggest that the alterations in gut microbiota due to the high-fat diet had a direct impact on the rats’ anxiety-related responses.

“Everyone knows that these are not healthy foods, but we tend to think about them strictly in terms of a little weight gain,” said lead author Christopher Lowry, a professor of integrative physiology at University of Colorado Boulder. “If you understand that they also impact your brain in a way that can promote anxiety, that makes the stakes even higher.”

On a molecular level, the study found that the high-fat diet affected the expression of specific genes involved in serotonin production and signaling in the brain. The high-fat diet group showed increased expression of genes such as tph2, htr1a, and slc6a4 in the brainstem’s dorsal raphe nucleus. These genes are involved in the synthesis and signaling of serotonin, a neurotransmitter often associated with feelings of well-being and happiness. However, increased expression of these genes can also be linked to anxiety, suggesting that the high-fat diet created a brain chemical environment conducive to anxiety.

“To think that just a high-fat diet could alter expression of these genes in the brain is extraordinary,” said Lowry. “The high-fat group essentially had the molecular signature of a high anxiety state in their brain.”

The researchers hypothesize that the disrupted gut microbiota might compromise the gut lining, 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 findings 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’s limitations include its reliance on an animal model, which may not fully replicate human physiology and behavior. Future research should aim to confirm these results in human subjects, explore the specific gut-brain communication mechanisms, and examine the impact of different types of dietary fats.

“Considering the early introduction of high-fat foods in children’s diets, and the ever-increasing obesity epidemic, our data introduce a possible scenario by which the dietary choices during adolescence can influence the gut microbiome, brainstem serotonergic systems, and the susceptibility to the development of psychiatric disorders in adulthood. This knowledge could lead to new microbiome-based approaches to prevent stress-related psychiatric disorders such as anxiety disorders,” the researchers concluded.

The study, “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.