Excessive Oral Intake of Vitamin B12 Alters Microbe-host Interactions That Stimulate Citrobacter Rodentium Growth and Virulence in Mice.

Background: Vitamin B12 supplements typically contain doses that far exceed the recommended daily amount, and high exposures are generally considered safe. Competitive and syntrophic interactions for B12 exist between microbes on the gut. Yet, it has to be established to what extent excessive levels affect the gut microbiota and infection resistance. The objective of this study was to evaluate the effect of excess B12 on microbial ecology and pathogen virulence. Mice were fed a standard chow diet and received either water or water supplemented with B12 (cyanocobalamin; ~120 mg/day) and were subsequently challenged with Citrobacter rodentium, a mouse-specific pathogen. Infection severity was determined by body weight, pathogen load, and histopathologic scoring. Host biomarkers of inflammation were assessed in the colon before and after the pathogen challenge.Results: Cyanocobalamin supplementation led to an enhanced pathogen colonization at day 1 (P < 0.05) and day 3 (P < 0.01) post-infection. The impact of B12 on gut microbial communities, although minor, was distinct and attributed to the changes in the Lachnospiraceae populations and reduced alpha diversity. Cyanocobalamin treatment disrupted the activity of the low-abundance community members of the gut microbiota. It enhanced the amount of interleukin-12 p40 subunit protein (IL12/23p40; P < 0.001) and interleukin-17a (IL-17A; P < 0.05) in the colon of naïve mice. This immune phenotype was microbe-dependent, and the response varied based on the baseline microbiota. The cecal metatranscriptome revealed that excessive cyanocobalamin decreased the expression of glucose utilizing genes by C. rodentium, a metabolic attribute previously associated with pathogen virulence. Conclusions: Cyanocobalamin supplementation enhanced the ability of C. rodentium to colonize the gut by impacting the microbe-host interactions that normally help to protect against pathogen colonization. This research provides insights into vitamin B12 supplementation and highlights potential consequences of over-supplementation.