This study reinforces that diet profoundly influences the gut microbiome. An imbalanced microbiome can cause a cascade of negative effects, including inflammation, obesity, and increased vulnerability to psychiatric disorders such as anxiety. This highlights the importance of healthy dietary choices to maintain the microbiome in balance and protect physical and mental health.
Obesity and anxiety disorders have been frequently found together and represent health conditions on the rise in modern urban societies.
These two conditions are known as comorbidities, meaning they often occur together and share risk factors or underlying biological mechanisms. One such factor is inflammation, which appears to play a major role in this relationship.
Animal studies suggest that a high-fat diet (HFD) may increase neuroinflammation, an inflammation that occurs in the brain, and intensify anxiety-related behaviors.
For example, in experiments with rats fed a high-fat diet, greater neuroinflammation was observed in regions of the brain that regulate anxiety-related defense behaviors.
While the exact mechanisms by which high-fat diets influence neuroinflammation and anxiety-like behaviors are not yet fully understood, changes in the gut-brain microbiome (GMB) axis are thought to play a crucial role.
This axis refers to the bidirectional connection between the gut microbiota (the community of microorganisms in the intestine), the central nervous system, and the brain. Changes caused by high-fat diets can alter the diversity and composition of the gut microbiome, affecting immunity, inflammation, and even cognitive function.
When the gut microbiome experiences an imbalance in its diversity or composition, a condition called gut dysbiosis occurs.
This dysbiosis not only increases inflammation in the body and brain (neuroinflammation), but also affects the production and function of serotonin, a neurotransmitter that is key to regulating mood and emotions.
The quantity and diversity of microorganisms found in the intestinal microbiota contribute to maintaining health throughout the organism, and an imbalance of these factors (which characterizes a dysbiosis) may be related to the development of several diseases. Source: Source: Heather. https://thespicyapron.com/dysbiosis-diet/
Serotonin is known to modulate emotional behaviors, including defensive and anxious responses. The main source of serotonin in the brain is the dorsal raphe nucleus (DR), a region crucial for emotional regulation.
Studies show that activating specific parts of this nucleus, such as the dorsal raphe nucleus (cDRD), can increase anxiety-like behaviors.
Previous research has shown that high-fat diets can alter serotonergic signaling. For example, rats fed HFD had elevated levels of serotonin in the hippocampus, a region associated with memory and emotional processing.
Serotonin pathways in the brain. Image: Catherine C
Serotonin-related genes such as TPH2, HTR1A and SLC6A4 also appear to be involved.
The TPH2 gene is responsible for the production of tryptophan hydroxylase 2, an enzyme crucial for the synthesis of serotonin in the central nervous system.
The HTR1A gene, which encodes the 5-HT1A receptor, regulates the release and synthesis of serotonin, and is associated with disorders such as generalized anxiety and panic.
The SLC6A4 gene controls the reuptake of serotonin in synapses, affecting its availability in the brain, and is linked to temperamental traits linked to anxiety and depression.
Based on these findings, scientists at the Federal University of Ouro Preto, Brazil, investigated how high-fat diets can alter the gut microbiome, influence the expression of serotonin-related genes and increase anxiety-like defensive behaviors.
In this study, male Wistar rats were fed high-fat diets (HFD) for nine weeks.
The results showed that HFD reduced the diversity of the gut microbiome and altered its composition. Specifically, there was an increase in the proportion of Firmicutes bacteria relative to Bacteroidetes.
Firmicutes are known for their ability to extract more energy from food, especially fats and complex carbohydrates. This increase is associated with weight gain, obesity and inflammatory processes.
On the other hand, Bacteroidetes, which help regulate weight and metabolize fiber, had their proportion reduced, indicating a negative impact of the high-fat diet on metabolic balance.
Another important finding was the increase in the levels of Blautia, a bacterium belonging to the Firmicutes phylum. Blautia is often associated with inflammatory processes and unfavorable metabolic conditions, such as insulin resistance and obesity. This increase suggests that the high-fat diet favors bacteria that can contribute to inflammatory states that are harmful to health.
In addition, the study recorded a reduction in bacteria of the Prevotella genus, which belong to the Bacteroidetes phylum. These bacteria are typically found in high-fiber diets and play a crucial role in the digestion of vegetables and the production of short-chain fatty acids.
These compounds have anti-inflammatory properties and are essential for gut health. The reduction in Prevotella reflects the impact of a low-fiber diet, such as a HFD, on protecting against inflammation and maintaining the integrity of the microbiome.
These changes in the microbiome are consistent with patterns observed in human populations in industrialized societies, which often consume high-fat, low-fiber diets. Such diets contribute to increased obesity, metabolic diseases, and psychiatric disorders such as anxiety.
Microbial phyla living in your gut microbiome. Source: Rupa Health
In addition, HFD increased the expression of the TPH2, HTR1A, and SLC6A4 genes in specific brainstem regions, including the cDRD. This change was associated with increased anxiety-related defensive behaviors in the mice.
The study also identified that certain gut bacteria were directly linked to these changes in serotonergic gene expression.
These findings suggest that obesity induced by high-fat diets is linked to changes in the microbiome-gut-brain axis, influencing both the serotonergic system and anxiety-related behaviors.
Another relevant aspect of the study was the observation that the microbiome changes induced by HFD are similar to those found in human microbiomes consuming modern diets rich in processed and fatty foods.
This pattern may explain how dietary choices made during adolescence, a critical period of development, impact the gut microbiome and predispose individuals to psychiatric disorders such as anxiety and depression in adulthood.
The study concludes that these findings pave the way for new approaches to treating stress-related disorders. For example, microbiome-based therapies, such as probiotics or specific diets, could be developed to prevent or reduce the effects of psychiatric disorders associated with obesity.
Given the global rise in obesity and the early introduction of high-fat foods into children’s diets, these data highlight the importance of early interventions to promote healthy eating habits and protect long-term mental health.
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High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats
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 & Rodrigo Cunha de Menezes
Biological Research, volume 57, Article number: 23 (2024)
Abstract:
Obesity, associated with the intake of a high-fat diet (HFD), and anxiety are common among those living in modern urban societies. Recent studies suggest a role of microbiome-gut-brain axis signaling, including a role for brain serotonergic systems in the relationship between HFD and anxiety. Evidence suggests the gut microbiome and the serotonergic brain system together may play an important role in this response. Here we conducted a nine-week HFD protocol in male rats, followed by an analysis of the gut microbiome diversity and community composition, brainstem serotonergic gene expression (tph2, htr1a, and slc6a4), and anxiety-related defensive behavioral responses. We show that HFD intake decreased alpha diversity and altered the community composition of the gut microbiome in association with obesity, increased brainstem tph2, htr1a and slc6a4 mRNA expression, including in the caudal part of the dorsomedial dorsal raphe nucleus (cDRD), a subregion previously associated with stress- and anxiety-related behavioral responses, and, finally, increased anxiety-related defensive behavioral responses. The HFD increased the Firmicutes/Bacteroidetes ratio relative to control diet, as well as higher relative abundances of Blautia, and decreases in Prevotella. We found that tph2, htr1a and slc6a4 mRNA expression were increased in subregions of the dorsal raphe nucleus in the HFD, relative to control diet. Specific bacterial taxa were associated with increased serotonergic gene expression in the cDRD. Thus, we propose that HFD-induced obesity is associated with altered microbiome-gut-serotonergic brain axis signaling, leading to increased anxiety-related defensive behavioral responses in rats.
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