(P30-024-25) Serum Methylmalonic Acid Is Associated With Gut Microbial Co-Abundance Guilds and Circulating Propionate in Healthy Adults

Objectives: Methylmalonic acid (MMA) is a specific functional biomarker of vitamin B12 status, but is also influenced by renal function and age. Oral antibiotics reduce serum MMA suggesting that gut microbes, particularly those that produce the MMA precursor, propionate, may also be relevant. Herein, we investigated the associations among gut microbes, B12, MMA, and propionate.

Methods: The study sample consisted of healthy adults (N=100, 18-81y). Gut microbes were profiled at the amplicon sequence level using 16S rRNA gene V4 amplicon sequencing. Serum B12 was measured by chemiluminescence assay, serum MMA by LC-MS/MS, and plasma short chain fatty acids (SCFAs) by GC-MS/MS. Microbial co-abundance guilds were identified using a dichotomic and tree-based group identification method. Random forest regression was used to identify microbial co-abundance guilds which predict measured B12 and MMA adjusting for age, sex, BMI, creatinine, and supplement B12. Multivariate linear regression was used to assess associations between SCFAs and MMA adjusting for B12, age, sex, creatinine, BMI, and fiber intake.

Results: Mean ± SD B12, MMA and propionate concentrations were 349 ± 143 pmol/L, 161 ± 119 nmol/L, and 1.34 ± 0.76 µmol/L. 28 microbial co-abundance guilds were identified. Supplement B12 and guilds 10 and 15 were predictors of B12 (p < 0.0001) and guild 13 was a predictor of MMA (p = 0.01). Propionate explained 12.6% of the study sample variance in MMA (R² = 0.126; p = 0.0003). After controlling for covariates, the association with propionate remained significant (p = 0.002) with the full model explaining 31.1% of the variance in MMA (R² = 0.311). No associations between other SCFAs and MMA were found.

Conclusions: Different microbial co-abundance guilds are predictive of B12 versus MMA. Thus, some variance in MMA is not specific to B12 availability, which has ramifications for using MMA as specific indicator of B12 status. Moreover, propionate was a determinant of a significant percentage of the variance in MMA. This association was unique to propionate among the SCFAs. These results may have relevance to recent findings describing independent associations of MMA with other conditions including cancer, cardiovascular, and neurodegenerative diseases.

Funding Sources: Rutgers Univ. Busch Biomedical Grant