A reader ask me about methylation. In 2013, I did a post “methylation cycle gut bacteria and chronic fatigue syndrome” which found that E.Coli and Bacillus subtilis are both involved in methylation. CFS patients are very low in both, additionally, I posted in 2015 about Methylation Testing via 23andMe.com
Methylation has been a hot topic for a number of years in the CFS community and other medical areas. For example, Dr. Myrna Hill has written a page about it for CFS patients and cite “Rich van Konynenburg has identified a package of micronutrients specifically to support the methylation cycle”. Rich was very active in this area until he passed away in Sept 2012. There is a lot of his material on line. He was inspired by the work of Dr Amy Yasko.
In the month before he died, we had started discussing the role of the microbiome in methylation. I will attempt touch a few items only (there are over 88000 studies on pubmed)
DNA is a factor, but..
- “methylation is regulated by a family of DNMTs: DNMT1, DNMT2, DNMT3A, DNMT3B, and DNMT3L.7–11 [2011}
- PITX2 and PANCR DNA methylation predicts overall survival in patients with head and neck squamous cell carcinoma .
- Hypomethylation of HLA-DRB1 and its clinical significance in psoriasis .
Epigenetics is also another factor
Epigenetics is modification of DNA’s behavior due to environmental events and stress. You may have DNA that disposes you towards methylation issues — but it takes the right set of events to cause methylation issues. Sometimes this activation can persist for generations. Note that environmental includes shifts of the microbiome.
- Pregnant women’s cognitive appraisal of a natural disaster affects their children’s BMI and central adiposity via DNA methylation: .
- Epigenome-wide DNA methylation analysis in siblings and monozygotic twins discordant for sporadic Parkinson’s disease revealed different epigenetic patterns in peripheral blood mononuclear cells .
- Changes in methylation of genomic DNA from chicken immune organs in response to H5N1 influenza virus infection . – an infection can alter methylation!
What about CFS and related conditions?
- Epigenome-wide DNA methylation patterns associated with fatigue in primary Sjögren’ssyndrome .
- “A total of 251 differentially methylated CpG sites were associated with fatigue. The CpG site with the most pronounced hypomethylation in pSS high fatigue annotated to the SBF2-antisense RNA1 gene.”
- Chronic Fatigue Syndrome and DNA Hypomethylation of the Glucocorticoid Receptor Gene Promoter 1F Region: Associations With HPA Axis Hypofunction and Childhood Trauma .
- “Overall NR3C1-1F DNA methylation was lower in patients with CFS than in controls.”
- “We found evidence of NR3C1 promoter hypomethylation (low methylation) in female patients with CFS and the functional relevance of these differences was consistent with the hypothalamic-pituitary-adrenalaxis hypofunction hypothesis (GR hypersuppression). However, we found no evidence of an additional effect of childhood trauma on CFS via alterations in NR3C1 methylation.”
- DNA methylation modifications associated with chronic fatigue syndrome .
- “We found an increased abundance of differentially methylated genes related to the immune response, cellular metabolism, and kinase activity. Genes associated with immune cell regulation, the largest coordinated enrichment of differentially methylated pathways, showed hypomethylation within promoters and other gene regulatory elements in CFS. These data are consistent with evidence of multisystem dysregulation in CFS and implicate the involvement of DNA modifications in CFS pathology.”
- Acute psychosocial stress-mediated changes in the expression and methylation of perforin inchronic fatigue syndrome.
- “These findings suggest methylation could be an important epigenetic determinant of inter-individual differences in PRF1 expression and that the differences in PRF1 expression and methylation between CFS and non-fatigued (NF) controls in the acute stress response (to Trier Social Stress Test) require further investigation.”
- Epigenetic alterations and an increased frequency of micronuclei in women with fibromyalgia .
- “The majority of differentially methylated (DM) sites (91%) were attributable to increased values in the women with FM. The DM sites included significant biological clusters involved in neuron differentiation/nervous system development, skeletal/organ system development, and chromatin compaction. Genes associated with DM sites whose function has particular relevance to FM included BDNF, NAT15, HDAC4, PRKCA, RTN1, and PRKG1. Results support the need for future research to further examine the potential role of epigenetic and acquired chromosomal alterations as a possible biological mechanism underlying FM.”
And… the microbiome?
- The relationship between early-life environment, the epigenome and the microbiota .
- ” Epigenetics can change gene expression to modify disease risk; unfortunately, how epigenetics are changed by the environment is unclear. It is known that the environment modifies the microbiota, and recent data indicate that the microbiota and the epigenome interact and respond to each other. Specifically, the microbiome may alter the epigenome through the production of metabolites. Investigating the relationship between the microbiome and the epigenome may provide novel understanding of the impact of early-life environment on long-term health.”
- Epigenetic imprinting by commensal probiotics inhibits the IL-23/IL-17 axis in an in vitro model of the intestinal mucosal immune system .
- “ Bifidobacterium breve (DSMZ 20213) and Lactobacillus rhamnosus GG (ATCC 53103) may exert their anti-inflammatory effects in the gut by down-regulating the expression of the IBD-causing factors (IL-23/IL-17/CD40) associated with epigenetic processes involving the inhibition of histone acetylation and the optimal enhancement of DNA methylation, reflected in the limited access of NF-κB to gene promoters and reduced NF-κB-mediated transcriptional activation. …
- We describe a new regulatory mechanism in which commensal probiotics inhibit the NF-κB-mediated transcriptional activation of IBD-causing factors (IL-23/IL-17/CD40), thereby simultaneously reducing histone acetylation and enhancing DNA methylation.
Methylation is a very complex area. One path is that of supplements intending to help — think of this as taking B12, except you are taking methylated-B12. 1000 mcg/ 1 mg seems to be the effective ongoing dosage for B12, see this post. The other path is altering the microbiome to enhance methylation — the equivalent of taking Lactobacillus Reuteri to produce your own B12. Of course, you can do both at the same time. The first path will provide temporary symptom relief, the second path raise the prospect of a permanent correction of methylation issues.
There are four probiotic species that are indicated as good candidates:
- E.Coli (Symbioflor-2 or Mutaflor)
- Bifidobacterium breve (DSMZ 20213)
- Lactobacillus rhamnosus GG (ATCC 53103) – aka Culturelle
- Bacillus subtilis