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. 2020 Jan 14;17:21. doi: 10.1186/s12974-019-1667-1

Table 2.

List of metabolites released by microbiota

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].

ROS reactive oxygen species, NH3 ammonia, LINE-1 long interspersed element-1, TET ten–eleven translocation

Adapted from Mischke et al. [147]