Oral vitamin B 12 supplement is delivered to the distal gut, altering the corrinoid profile and selectively depleting Bacteroides in C57BL/6 mice.

Vitamin B ₁₂ is a critical nutrient for humans as well as microbes. Due to saturable uptake, high dose oral B ₁₂ supplements are largely unabsorbed and reach the distal gut where they are available to interact with the microbiota. The aim of this study was to determine if oral B ₁₂ supplementation in mice alters 1) the concentration of B ₁₂ and related corrinoids in the distal gut, 2) the fecal microbiome, 3) short chain fatty acids (SCFA), and 4) susceptibility to experimental colitis. C57BL/6 mice (up to 24 animals/group) were supplemented with oral 3.94 µg/ml cyanocobalamin (B ₁₂ ), a dose selected to approximate a single 5 mg supplement for a human. Active vitamin B ₁₂ (cobalamin), and four B ₁₂ -analogues ([ADE]CN-Cba, [2Me-ADE]CN-Cba, [2MeS-ADE]CN-Cba, CN-Cbi) were analyzed in cecal and fecal contents using liquid chromatography/mass spectrometry (LC/MS), in parallel with evaluation of fecal microbiota, cecal SCFA, and susceptibility to dextran sodium sulfate (DSS) colitis. At baseline, active B ₁₂ was a minor constituent of overall cecal (0.86%) and fecal (0.44%) corrinoid. Oral B ₁₂ supplementation increased active B ₁₂ at distal sites by >130-fold (cecal B ₁₂ increased from 0.08 to 10.60 ng/mg, fecal B ₁₂ increased from 0.06 to 7.81 ng/ml) and reduced microbe-derived fecal corrinoid analogues ([ADE]CN-Cba, [2Me-ADE]CN-Cba, [2MeS-ADE]CN-Cba). Oral B ₁₂ had no effect on cecal SCFA. Microbial diversity was unaffected by this intervention, however a selective decrease in Bacteroides was observed with B ₁₂ treatment. Lastly, no difference in markers of DSS-induced colitis were detected with B ₁₂ treatment.