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Table 2 List of metabolites released by microbiota

From: Aberrant DNA methylation profile exacerbates inflammation and neurodegeneration in multiple sclerosis patients

Metabolite

Effect on DNA methylation

p-Cresol

It induces the expression of DNA methyltransferases 1, 3a, and 3b and it is associated with CpG hypermethylation of Klotho gene [152], a regulator of vitamin D metabolism [153].

Hydrogen sulphide (H2S)

Involved in the neutralisation of ROS. It increases DNA methylation [154].

Riboflavin (vitamin B2)

Pyridoxine (vitamin B6)

Cobalamin (vitamin B12)

Cofactor involved in DNA methylation metabolism [155, 156].

Folate (vitamin B9)

It acts as a methyl donor involved in DNA methylation metabolism [155, 156].

It reduces the activity of DNA methyltransferase [157].

Choline

It acts as a methyl donor that can be recruited by human gut microbiota, reducing its availability [158].

Involved in DNA methylation and gene expression in murine colitis model, an inflammatory disease [159].

Betaine

It acts as a methyl donor involved in DNA methylation reactions [156, 160].

Associated with changes in DNA methyltransferases and coupled with changes in DNA methylation [161].

Ammonium (NH4)

Inverse correlation between faecal NH3 and LINE-1 gene methylation [162].

α-ketoglutarate

Involved in (de)methylation as a co-factor of histone demethylases and TET family [163, 164].

L-ascorbic acid (vitamin C)

It exerts a strong influence on active DNA demethylation. It enhances TET-mediated generation of 5-hydroxymethylation [165].

  1. ROS reactive oxygen species, NH3 ammonia, LINE-1 long interspersed element-1, TET ten–eleven translocation
  2. Adapted from Mischke et al. [147]