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

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When feeling stressed, many people turn to high-fat, high-sugar comfort foods. However, a recent study from the University of Colorado at 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 alter gut bacteria, disrupt 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 that links the gastrointestinal tract and the brain. Researchers are increasingly interested in how this connection influences mental health, particularly through the gut microbiome, which consists of trillions of bacteria that live in our intestines. Previous research has shown that the composition of gut bacteria can significantly impact both physical and mental health, including conditions such as obesity, anxiety, and depression.

Since obesity and anxiety disorders often occur together and their prevalence is increasing, the researchers set out to explore whether diet could be a common factor influencing both conditions. Specifically, they wanted to investigate whether a high-fat diet, which is common in many modern diets, could alter the gut microbiome in a way that affects brain function and behavior. Understanding these mechanisms could provide insight 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 adolescents, 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 approximately 11% fat, while the other group was given a high-fat diet containing 45% fat, mostly from saturated animal fats. The duration of the dietary intervention was nine weeks, a significant portion of the rats’ lives, equivalent to several years in human terms.

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During the study, researchers collected weekly fecal samples 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 important bacterial groups known to be influenced by diet and associated with health outcomes.

After the nine-week diet 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 rats’ willingness to explore the open, elevated arms of a maze, and other tests that measure responses to stress and novel 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 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 worse health outcomes. The high-fat diet group showed a higher proportion of Firmicutes to Bacteroidetes, a shift in balance often linked to obesity and metabolic disorders.

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 such as the elevated plus maze, where rats on the 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.

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“We all know these foods are unhealthy, but we tend to think of them strictly in terms of a small weight gain,” said senior author Christopher Lowry, a professor of integrative physiology at the University of Colorado at Boulder. “If we understand that they also affect the brain in a way that can lead to anxiety, that makes the risks even greater.”

At the 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 dorsal raphe nucleus of the brain stem. 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 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 alter the expression of these genes in the brain is extraordinary,” Lowry said. “The high-fat diet group basically had the molecular signature of a heightened state of anxiety in the brain.”

The researchers hypothesize that altered gut microbiota could 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 anxiety-like behaviors observed. 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.

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Limitations of the study include its reliance on an animal model, which may not fully reproduce human physiology and behavior. Future research should aim to confirm these results in human subjects, explore the specific mechanisms of gut-brain communication, and examine the impact of different types of dietary fats.

“Considering the early introduction of high-fat foods into children’s diets and the ever-increasing obesity epidemic, our data present a possible scenario whereby dietary choices during adolescence may influence the gut microbiome, brainstem serotonergic systems, and susceptibility to developing 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 concluded.

The study, “High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats“The New York Times” was written 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.

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