Inverse association between serum vitamin B12 level and abundance of potential B12-producing gut microbes in Indian children

Background: The human gut microbiome is a natural source of essential micronutrients like B-vitamins, which are utilized by both the host and other community members. The prevalence and abundance of known B-vitamin producers and B-vitamin biosynthesis pathways have already been reported in gut microbiome cohorts of a few countries including India. Objective: To test whether the presence of B-vitamin producers/biosynthetic pathways translates into serum B-vitamin levels, taking B12 as a case example. Methods: Fecal samples were collected from non-deficient (serum B12 level > 210 pg/mL, n=29) and B12 deficient (serum B12 level < 210 pg/mL, n=30) children from a tribal region of central India. Whole metagenomic DNA was extracted, sequenced, and analyzed for taxonomic profiling and diversity comparisons. Differentially abundant taxa between two groups were identified. The prevalence and abundance of potential B12 producers were compared, and their association with serum B12 level was established. Results: A comparison of within-sample diversity between the two groups did not show any difference; however, between-sample diversity was significantly less in the B12 deficient group. Differential abundance testing also showed different microbiome structure in the B12 deficient group, where an increased abundance of B12 transporter-carrying Bacteroides thetaiotaomicron, a few pathogenic species, and ten known B12 producers was observed. Potential B12 producers were also significantly prevalent and abundant in the deficient group. Their cumulative abundance was also significantly higher in the deficient group and showed a negative association with serum B12 levels. Conclusion: A higher abundance of potential B12 producers in the deficient group suggested an adaptive mechanism by the gut microbiome to meet the B12 requirements of the community, by selectively promoting the growth of B12 producers.