Associations between Biomarkers of Vitamin B12 Status and Gut Microbial Guilds in a Cohort of Australian Adults.

BACKGROUND

Vitamin B12 (B12) is an essential nutrient required for hematological and neurological function. Human gut microbes either synthesize B12 or use B12 consumed by hosts. Consequently, variation in gut microbiota may influence B12 status in humans.

OBJECTIVES

The goal was to assess associations between gut microbiota and serum B12 and a functional biomarker of B12 status, methylmalonic acid (MMA).

METHODS

In 90 adults (44 males/46 females; 20-75 y) living in Sydney, Australia, 16S ribosomal ribonucleic acid gene V3-V4 amplicon sequencing was used to profile gut microbiota at the amplicon sequence variant (ASV) level. B12 was measured by automated chemiluminescence and MMA by high-pressure liquid chromatography-tandem-mass spectrometry. Associations between tertiles of B12 and MMA and microbial alpha and beta diversity and overall microbiota composition were assessed. Microbial guilds were identified via coabundance analysis on ASVs. Multivariate linear regression and random forest regression were used to assess the associations between guilds and the B12 biomarkers, controlling for age, sex, body mass index, and fiber intake.

RESULTS

Mean serum B12 and MMA were 389 ± 177 pmol/L and 210 ± 80 nmol/L, respectively. Gut microbial diversity and richness were significantly associated with B12 tertiles (Shannon index: P = 0.010; Faith's phylogenetic diversity: P = 0.048; ASV number: P = 0.022). No associations were observed between B12 tertiles and beta diversity or between MMA tertiles and alpha or beta diversity. Thirty guilds were identified, with 2 guilds and age included in the final model predictive of B12 (P = 0.03), and 3 different guilds and no covariates included in the final model predictive of MMA (P = 0.003).

CONCLUSIONS

These results indicate that different guilds are predictive of serum B12 compared with serum MMA. This suggests that some of the variance in serum MMA in adults is not specific to B12 status, which has ramifications for interpreting MMA as a marker of B12 status.