4-ethylphenylsulfate {60000094}

Shared Reference Notes

• [1.1] 
  - mice exposed to 4EPS displayed #Anxiety-like behaviours, and pharmacological treatments that promote oligodendrocyte differentiation prevented the behavioural effects of 4EPS. - the microbial metabolite 4-ethylphenyl sulfate (4EPS) were increased in a mouse model of atypical neurodevelopment. - 4EPS entered the brain and was associated with changes in region-specific activity and functional connectivity. - Gene expression signatures revealed altered oligodendrocyte function in the brain, and 4EPS impaired oligodendrocyte maturation in mice and decreased oligodendrocyte–neuron interactions in ex vivo brain cultures.
• [1.2] 
  - administration of 4-ethylphenylsulfate (4-EPS), a #Tyrosine derivative, to mice at 3–6 weeks postnatal induced #Anxiety-like behavior. - 4-EPS interfered with oligodendrocyte maturation, myelination, and brain activity patterns.
• [1.3] [#Autism] 
  - 4-ethylphenylsulfate, which is a dietary #Tyrosine metabolite that is considered to induce ADS-like behavior
• [1.4] [#Autism] 
  - High blood concentrations of host-modified 4EP, #4-ethylphenol #Sulfate [4EPS], are associated with an #Anxiety phenotype in autistic individuals. - accumulation of 4EPS in the brain of mice affects connectivity between subregions, particularly those linked to #Anxiety
• [#Autism, #Blood Brain Barrier Integrity] [#4-ethylphenol] - increased intestinal permeability is common in autistic individuals, potentially explaining increased flux of 4EP and/or 4EPS across the gut epithelium and the Blood Brain Barrier [BBB].
• [#Autism] [#4-ethylphenol] - #Clostridium spp. are highly abundant in autistic individuals and yield 4EP precursors.
• [#4-ethylphenol] - A subset of the required enzymes (e.g., hydroxycinnamate reductase enzymes (HCRs), #Tyrosine #Ammonia-lyase (TALs)) are encoded within the genomes of many microbes (e.g., #Clostridium aerotolerans, #Clostridium xylanolyticum and #Bacteroides ovatus) > increase 4EP
• [#Clostridium aerotolerans] [#4-ethylphenol] - other enzymes (e.g., vinylphenol reductase protein (VPR)) are rarer and encoded by only a few microbes (i.e., #Lactobacillus plantarum, C. aerotolerans DSM 5434T and #Brettanomyces (Dekkera) yeasts) > increase 4EP
• [1.5] [#Bacteroides ovatus] 
  - B. ovatus is a primary producer of a precursor to 4EPS and increased #Anxiety behaviors in mice.
• [#Bacteroides fragilis] - B. fragilis, was able to ameliorate #Autism spectrum disorder (ASD)–like symptoms in a mouse model by consuming a microbially dependent metabolite 4-ethylphenylsulfate (4EPS)
• [1.6] [#Autism] 
  - #4-ethylphenol (4-EP), produced by gut bacteria, is converted into 4-ethylphenyl sulfate (4-EPS) in the host liver and accumulates in the brain, resulting in ASD symptoms

References Notes