High dietary B12 is associated with reduced gut microbial B12 biosynthesis capacity and lower fecal short-chain fatty acids in healthy United States adults.

Vitamin B12 is acquired through the consumption of animal-source foods and supplements. In animal models, interventions with B12 and/or methionine influence fecal short-chain fatty acid (SCFA) concentration. Yet the relevance of dietary B12 to microbially produced SCFAs in humans is unknown. This study determined associations between dietary B12 and the gut microbiome in a deeply phenotyped cohort of healthy U.S. adults. Habitual diet and fecal shotgun metagenomes were integrated alongside measurements of fecal SCFAs, plasma SCFAs, and plasma B12 (n = 277). Vitamin B12 intake ranged from 2.4 to 1062 µg/day, and nearly all participants were B12 replete. Stratification of participants into adequate (2.4-8.51 µg/day) and high B12 intake (>8.51 µg/day) groups revealed the association of high intake with a reduction in bacteria capable of anaerobic B12 biosynthesis. High B12 intake was also associated with lower fecal SCFA concentrations even after controlling for fiber and methionine intake. Differences in microbial taxa between dietary groups were limited. However, machine learning models demonstrated the ability to predict fecal propionate and butyrate from microbial pathways in the adequate or no supplement groups, but not in the high intake or supplement groups. Our results indicate that dietary B12 greater than 8.51 µg/day may be associated with reduced microbial synthesis of B12 and lower fecal SCFA production.