This is a study linking slow DNA methylation and leaky gut

Discussion in 'News and Research' started by ljimbo42, Aug 19, 2014.

  1. ljimbo42

    ljimbo42 Member

    This study basically says that slow DNA methylation can cause "loss of epithelial integrity or barrier function" also known as leaky gut. I believe that getting the methylation cycle optimized is central to healing from CFS/FM. Here is the study-http://genesdev.cshlp.org/content/28/6/652.short
    All the best......... Jim
  2. IanH

    IanH Active Member

    Am I missing something? what has this to do with "leaky gut"?
  3. ljimbo42

    ljimbo42 Member

    Hi Ian- The way I understand the study is that slow DNA methylation leads to slow differentiation of intestinal stem cells to actual intestinal epithelium cells. This causes a "loss of epithelial integrity or barrier function" also called leaky gut. Does this make sense?
  4. IanH

    IanH Active Member

    Yes but this study was about epithelial crypt cell differentiation. The barrier is the epithelium and leads to increased risk of CRC. The tight junctions are a different set of cells again - allowing material to pass through the epithelium. I am not sure how epithelial crypt cell differentiation relates to tight junction function. However it is certainly possible that poor DNA methylation does affect tight junctions - but I don't know of any research to this effect. I was hoping to get some answers.

    Generally "leaky gut" seems to refer to loss of integrity of the tight junctions but I suppose could be extended to the whole epithelium. If breakdown of epithelial barrier function is a risk factor for CRC then it could also be a way toxins are penetrating.

    Paneth cells release the antimicrobial peptides and of course high vitamin D levels ensure that these cells function well and produce LL-37 and the defensins. Low levels of vitamin D (1,25(OH)2D are associated with leaky gut:

    http://www.ncbi.nlm.nih.gov/pubmed/17962355
  5. IanH

    IanH Active Member

    I suspect that the relationship between DNA-methylation and transcription is very complex and not simply related to the higher level chemistry of methionine and glutathione but is more related to infectious processes and immune derangement well known to occur in ME and FM.

    It is certainly the case that raising serum levels of S-AdenosylMet and glutathione have little effect on the symptoms of ME.

    Rnase-L is known to be elevated in ME and in many cases of FM.

    Rnase-L may have a relationship to disrupted methylation via its effect on R-Loops. R-loops are a loop formed during transcription where the nascent RNA connects to one strand of DNA leaving the other strand free within the loop. These loops are short, often only about 30bp long. These R-loops are affected by (and affect) various cell processes. No one has yet shown a relationship between Rnase-L and R-loop function but I suspect the chronic nature of ME and raised Rnase-L may affect their function and effects.

    Of course other explanation are possible that link Rnase-L to methylation because chronic upregulated Rnase-L might play a central role in the regulation of mRNA turnover which also shows some faults in ME.
    Last edited: Oct 7, 2014