Para-cresol {90000126}

Shared Reference Notes

• [1.1] 
  - Bacterial fermentation metabolite of tyrosine - Induction of inflammatory reactions and renal and cardiovascular impairment
• [1.2] [#Autism] 
  - The microbial metabolite p-Cresol induces selectively ASD core behavioral symptoms in mice. - Social behavior deficits induced by p-Cresol are dependant on changes in microbiota composition.
• [1.3] 
  - p-cresol derivatives and the tryptophan breakdown product #Indolepropionate, associated with the gut microbiome.
• [1.4] [#Autism] 
• [1.5] 
  - #TMAO is the hepatic oxidation product of the microbial trimethylamine (#TMA). - dietary supplementation with #TMAO was shown to promote atherogenesis and development of #Atherosclerosis in mice. - #TMAO levels associate with an increased risk of adverse cardiovascular events. - Carotid #Atherosclerosis was demonstrated to be associated with gut microbial metabolites (especially #TMAO and p-cresol sulfate) in >3,000 patients, which could serve as an independent predictor of the disease.
• [#Diabetes Type 2] - p-cresol was shown to have the potential to induce diabetes, with mice given p-cresol sulfate for four consecutive weeks showing an insulin-resistant phenotype.
• [1.6] 
  - Free #Phenol and p-cresol, most notably produced by Clostridium dificile, are the metabolic products of aromatic amino acids and are the biomarkers of a disturbed gut.
• [1.7] [#Candida albicans, #Clostridioides difficile] 
  - In the presence of C. Albicans, the opportunistic bacterium C. difficile can tolerate aerobic conditions, and the p-cresol produced by C. difficile inhibit C. Albian’s hypha formation, biofilm formation, and virulence. - This symbiotic relationship leads to more severe infection of C. difficile in mice models and increases IL-8 production in experimental intestinal epithelial cell-lines
• [1.8] [#Ceramides] [#Aging] 
  - Among metabolites that were positively associated with age, seven were common in all four groups (aconitic acid, #Choline, #Citrulline, #Cysteine, cystine, #kynurenine, and symmetric dimethylarginine (SDMA)) and 10 were common in three out of four groups (aspartic acid, asymmetric dimethylarginine (ADMA), butyrylcarnitine, ceramide d18:1/24:1, ceramide d18:1/25:0, ceramide d18:2/24:1, hippuric acid, homocysteine, methionine sulfoxide, and p-cresol #Sulfate)
• [1.9] 
  - p-Cresol, another #Tyrosine derivative and a metabolite, has also been directly associated with neurodevelopmental disorders.
• [#Clostridioides difficile, #Enterobacteriaceae bacterium] - A unique feature of C. difficile is the production of high concentrations of the antimicrobial compound para-cresol, which provides the bacterium with a competitive advantage over other bacteria found in the gut. - 4-Hydroxyphenylacetonitrile, significantly reducing C. difficile’s ability to compete with a gut dwelling Escherichia coli strain in competition-index assays, through a reduction in p-cresol production - 4-Hydroxyphenylacetonitrile > inhibitor of HpdBCA decarboxylase, > reduced p-cresol production by 99.0 ± 0.4%.
• [#Clostridioides difficile] - p-cresol selectively kills Gram-negative bacteria, which are relatively sensitive to p-cresol, whilst Gram-positive bacteria, such as C. difficile, are relatively tolerant to p-creso - ability to produce p-cresol is universal for C. difficile, with the HpdBCA pathway conserved in all five lineages. - C. difficile is one of only a few gut bacteria that produce p-cresol, therapeutics targeted against p-cresol could be highly specific to C. difficile
• [1.11] [#Clostridioides difficile] 
  - p-Cresol is an aromatic derivative of #Tyrosine produced as a catabolite by many members of the gut microbiota, including some #Bifidobacteriaceae, #Enterobacteriaceae, #Clostridiaceae, #Lactobacillaceae, #Coriobacteriaceae, and #Bacteroidaceae. - #Clostridia difficile has displayed a particular growth advantage on p-cresol and people with #Autism spectrum disorders often have a gut microbiome that is enriched in #Clostridia.
• [1.12] [#Phenol] 
  - Phenols, such as p-cresol, may be toxic for patients with underlying kidney diseases
• [1.13] [#Bifidobacterium infantis] 
  - Antibitic resulted dysbiosis > Application of synbiotic #Bifidobacterium longum subspecies infantis (B. infantis), and #Human milk oligosaccharides (HMOs) > - increases in #Lactate-consuming #Veillonella, faster #Acetate recovery, and changes in #Indolelactate and p-cresol #Sulfate, metabolites that impact host inflammatory status. - #Veillonella co-cultured in vitro and in vivo with B. infantis and HMO converts #Lactate produced by B. infantis to #Propionate, an important mediator of host physiology.
• [1.14] 
  - 4-methyl #Phenol and p-cresol, have been shown to have genotoxic effects on human enterocytes, reducing the integrity and longevity of the intestinal epithelium.
• [1.15] 
  - The absence of gut microbiota also reduces the production of amino acid-derived microbial metabolites (e.g., #Indole and p-cresol), which are reported to modulate #GLP-1 expression and secretion, and gut motility. - supplementing mice with the tyrosine-derived microbial metabolite p-cresol reversed the enteropeptidase inhibition mediated effects on Gcg expression and small intestinal transit.
• [1.16] [#Colitis] 
  - When p-cresol presents in excess in colonocytes, it inhibits mitochondrial #Oxygen consumption and consequently reduces cell proliferation. - when colonocytes were treated with p-cresol, anion superoxide production and DNA-double strand break were increased; thus, p-cresol is genotoxic.
• [1.17] [#Autism] 
  - #Phenol and p-cresol were higher in ASD patients
• [#Autism] [#Antibiotic Therapy] - p-cresol is hypothesized to exacerbate ASD severity and gut disorders, in the presence of intestinal infection, antibiotic consumption, and atypical intestinal permeability considered as potential p-cresol excess sources in ASD

References Notes