A reader asked “Can you please let me know whether probiotics can help reverse hypomethylation due to epigenetic changes?”

In plain english please!

Epigenetic means some environmental event turns off (or on) sections of your DNA (or bacteria is your guts) that produces methylation products. The most commonly known is likely Methylcobalamin (methylated B12). Very recent studies suggests that methylation has been reduced in CFS patients. What is an environmental event? could be a virus, an infection, a change of diet, change of hormones, etc.

Studies

• Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns[2018].
  • “Global DNA methylation levels of ME/CFS cases were similar to those of controls. …They also suggest a potential role of epigenetic de-regulation in the pathobiology of ME/CFS…”
• Integration of DNA methylation & health scores identifies subtypes in myalgic encephalomyelitis/chronic fatigue syndrome.[2018]
  • “ME/CFS subtypes are associated with specific DNA methylation differences and health symptomatology”
• Epigenome-wide DNA methylation patterns associated with fatigue in primary Sjögren’s syndrome.[2016]
  • “Some genes involved in regulation of the immune system and in inflammation are differently methylated in pSS patients with high vs low fatigue. “
• DNA methylation modifications associated with chronic fatigue syndrome.[2014]
  • “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.”
• Acute psychosocial stress-mediated changes in the expression and methylation of perforin in chronic fatigue syndrome.[2013]
  • “These findings suggest methylation could be an important epigenetic determinant of inter-individual differences in PRF1 expression”

Summary: Some (NOT ALL) CFS patients have differences in methylation.

Agents to cause epigenetic changes

• Hypomethylation of Epstein-Barr virus DNA in the nonproducer B-cell line EBR [1982].
  • DNA global hypomethylation in EBV-transformed interphase nuclei.[1999
  • Methylation of transcription factor binding sites in the Epstein-Barr virus latent cycle promoter Wp coincides with promoter down-regulation during virus-induced B-cell transformation.[2000]
• Arabidopsis displays centromeric DNA hypomethylation and cytological alterations of heterochromatin upon attack by pseudomonas syringae[2006]. 
• Chromosomal losses are associated with hypomethylation of the gene-control regions in the stomach with a low number of active genes. [2008]
• Combined inhaled diesel exhaust particles and allergen exposure alter methylation of T helper genes and IgE production in vivo.[2008]
• Infection with influenza A viruses causes changes in promoter DNA methylation of inflammatory genes.[2013]

Summary: If a person’s CFS onset is associated with EBV or Influenza, then they are more likely to be in one of the subsets found above.

Probiotics

The reader asked explicitly about probiotics. That’s a tough ask.

• The impact of probiotic supplementation during pregnancy on DNA methylation of obesity-related genes in mothers and their children.[2018]
  • “Probiotic supplementation led to significantly decreased levels of DNA methylation in 37 gene promoters and increased levels of DNA methylation in one gene promoter in women.”
  • What probiotics was not stated == I suspect Lactobacillus are the most likely.
• Bifidobacterium longum affects the methylation level of forkhead box P3 promoter in 2, 4, 6-trinitrobenzenesulphonic acid induced colitis in rats.
  • “B. Longum treatment changes the methylation level in Foxp3 promoter in TNBS-treated colitis rats, and significantly demethylates several CpG sites in Foxp3 promoter. “

E.Coli Probiotics

This older article suggests that E.Coli probiotics (Mutaflor, Symbioflor-2 : (US Source, World Wide Source) ) suggests that getting “fresh” E.Coli may improve hypomethylation.

• Biological role of DNA methylation: sequence-specific single-strand breaks associated with hypomethylation of GATC sites in Escherichia coli DNA[1986].
  • “in the normal E. coli cell, in which practically all GATC sites are methylated.. transient hypomethylation require the formation of specific single-strand (of DNA) breaks”

Going over to data punk….. we get the bad news… looking at end products only E.Coli produces this as an end product.

Bottom Line

IMHO, the whole methylation vector is an over the horizon ship that may not deliver actionable treatment for CFS for at least two decades (if ever).