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Cobalamin, Microbiota and Epigenetics

  • Joan JoryEmail author
Reference work entry

Abstract

Functional cobalamin (B12) status and assessment are inextricably intertwined with the human microbiome. Small bowel bacterial overgrowth can both cause and result from gastritis and alter dietary cobalamin absorption. Some bacterial species may produce human-inaccessible cobalamin corrinoids and may create competition for human-accessible cobalamin. Increased human-inaccessible corrinoids from bacterial production may raise the total corrinoid level assessed by the serum total cobalamin, limiting diagnostic utility and masking a deficiency of human-accessible cobalamin. Anaerobic bacteria may reverse the propionic to succinic acid pathway, converting methylmalonic acid back to propionic acid to release CO2; this could raise propionic acid and lower methylmalonic acid levels, limiting its diagnostic utility. Cobalamin deficiency limits enzymatic conversion of homocysteine to methionine and increases homocysteine levels. Increased homocysteine can be reduced by diversion into the transsulfuration pathway, limiting the diagnostic power of this metabolite. Finally, in the delicate balance between folate and cobalamin which regulates DNA synthesis, excess synthetic folate from public health policies can combine with bacterial folate production to mask the macrocytic anemia of cobalamin deficiency.

Small bowel bacterial overgrowth can increase propionic acid production and reduce cobalamin bioavailability. Both propionic acid administration and cobalamin deficiency can alter brain fatty acid levels and brain function and cause autistic symptomology. Essential fatty acid ratios can modify gut bacterial species which can, in turn, modify fatty acid composition and inflammation. Omega-3 supplementation can reverse many of the symptoms of propionic acid neurotoxicity. Cobalamin supplementation can raise omega-3 fatty acid levels in the brain and can improve autism symptomology. Therefore, there are strong epigenetic interrelationships among cobalamin and its enzymatic activity, propionic acid, essential fatty acids, folate, and the human bacterial microbiome.

Keywords

Autism spectrum disorder B12 Brain-derived neurotrophic factor Cobalamin Dysbiosis Methylation Methylmalonic acid Propionic acid Micronucleated lymphocytes Polyunsaturated fatty acid Short-chain fatty acids Small bowel bacterial overgrowth 

List of Abbreviations

AA

Arachidonic acid

ADHD

Attention deficit hyperactivity disorder

ASD

Autism spectrum disorder; B12 = cobalamin

BDNF

Brain-derived neurotrophic factor

DHA

Docosahexaenoic acid

EPA

Eicosapentaenoic acid

IF

Intrinsic factor

MCM

Methylmalonyl-CoA mutase

MDA

Malondialdehyde

MetH

Methionine synthase

MMA

Methylmalonic acid

MNL

Micronucleated lymphocytes MTHF = methyltetrahydrofolate

PPA

Propionic acid

PUFA

Polyunsaturated fatty acid

SAH

S-adenosylhomocysteine

SAM-e

S-adenosylmethionine

SCFA

Short-chain fatty acids

SIBO

Small bowel bacterial overgrowth

THF

Tetrahydrofolate

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Authors and Affiliations

  1. 1.GuelphCanada

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