User:Mgp75/4-Ethylphenyl sulfate

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** Everything underlined is my work, the non-underlined portion is from the original article.

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4-Ethylphenyl sulfate (4EPS) is a metabolite produced by gut bacteria, which can be toxic when present in large amounts. Elevated levels of this metabolite have been associated with some medical conditions including chronic kidney disease and autism.

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 Gut-Brain Axis 

4-Ethylphenyl sulfate is a compound produced by a type of bacteria called clostridia in the gut microbiome. The presence of this substance has been linked to anxiety in the host of that microbiome. This is possible through the existence of the gut-brain axis. The gut-brain axis is a two-way communication system that transfers information between the digestive system and the nervous system. It has recently become a prominent topic of research in many areas of science, among them neuroscience, psychology, and nutrition. It is theorized that bacteria in the gut, and the substances that they produce, can influence emotions and behavior through this axis. 4-ethylphenyl sulfate in the stomach appears to increase anxiety and potentially cause behaviors linked to Autism Spectrum Disorder (ASD).

 4EPS and Anxiety 

Administering 4-ethylphenyl sulfate to mice resulted in an increase in anxiety as compared to control mice, determined through tests that measure anxiety via variations in survival behaviors. For example, in the exposed field test, mice are placed in a box that has a more exposed center and a more obscured perimeter, simulating an open field with hiding places on the outsides. Mice that were administered 4-ethylphenyl sulfate spent significantly more time in the obscured region than control mice. This demonstrates an increase in anxiety in the former group because the mice were opting to hide in the obscured region, rather than explore in the exposed region. Similar results were found in the plus-shaped maze test— mice spent more time in the obscured arm than open arm— and the dark/light box test— mice spent more time in the dark region than the light region5. All of these behaviors show that the mice with 4-ethylphenyl sulfate were more anxious due to their increased tendencies to hide in the darker, less exposed regions of the enclosures.

 4EPS and Autism Spectrum Disorder 

This theory has also been studied in humans in relation to Autism Spectrum Disorder (ASD). A clinical trial investigating this idea orally administered a medication that absorbs 4-ethylphenyl sulfate and other phenol compounds to 30 children with ASD. This means that the mice that received the medication had no 4-ethylphenyl sulfate in their gut. This medication is called AB-2004, and it has previously been proven to reduce anxiety and anxiety-linked behaviors in mice. In order to measure anxiety, the Pediatric Anxiety Rating Scale (PARS) and the Aberrant Behavior Checklist (ABC) were used. These individuals who were administered the AB-2004 had a decrease in both anxiety and irritability5. In addition, there was a decline in the coupling of the amygdala, the fear-processing center of the brain, and the anterior cingulate cortex, which plays an important role in decision-making and conflict6. This reinforces the idea of the gut-brain axis, where the microbiota in the stomach can have a great influence on the connection patterns in the brain, thus affecting behavior.