Oral vitamin B12 supplement is delivered to the distal gut, altering the corrinoid profile and selectively depleting Bacteroides in C57BL/6 mice

• Published in: Gut Microbes Vol. 10; no. 6; pp. 654 - 662
• Main Authors: Kelly, Caleb J, Alexeev, Erica E, Farb, Linda, Vickery, Thad W, Zheng, Leon, Eric L, Campbell, Kitzenberg, David A, Battista, Kayla D, Kominsky, Douglas J, Robertson, Charles E, Frank, Daniel N, Stabler, Sally P, Colgan, Sean P
• Format: Report
• Language: English
• Published: Taylor & Francis 02.11.2019
• Subjects: colitis; Inflammatory bowel disease; microbiota; vitamin B12
• ISSN: 1949-0976; 1949-0984
• DOI: 10.1080/19490976.2019.1597667

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.