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Machine Learning · Journal article
Gut Microbes · August 21, 2026
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This cross-sectional study of 277 healthy U.S. adults found that dietary B12 intake above 8.51 µg/day was associated with reduced abundance of bacteria capable of anaerobic B12 biosynthesis and lower fecal short-chain fatty acid concentrations, even after controlling for fiber and methionine intake. Machine learning models could predict fecal propionate and butyrate from microbial pathways in the adequate B12 intake group but not in the high intake group, suggesting a threshold effect of dietary B12 on microbial SCFA production capacity.
Observational, cross-sectional cohort study. Healthy adult participants aged 18–65 years, balanced by sex and BMI (18.5–39.9 kg/m²). Exclusion: minor surgery, hospitalization, or antibiotics in prior 4 weeks; major surgery within 16 weeks; egg allergy; pregnancy or lactation; diagnosed chronic disease on medication.. Intervention: None; observational study of habitual dietary B12 intake stratified into adequate (2.4–8.51 µg/day) and high (>8.51 µg/day) intake groups.. Compared with: Dietary B12 intake; adequate versus high intake stratification at 8.51 µg/day threshold.. n = 277. United States (USDA Nutritional Phenotyping Study); location of recruitment centers not specified in truncated text..
Vitamin B12 intake ranged from 2.4 to 1062 µg/day across n=277 participants High dietary B12 intake (>8.51 µg/day) was associated with reduced bacteria capable of anaerobic B12 biosynthesis High B12 intake was associated with lower fecal SCFA concentrations after controlling for fiber and methionine intake
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The findings suggest that excessive dietary B12 supplementation (>8.51 µg/day) may paradoxically reduce microbial B12 biosynthesis capacity and lower fecal short-chain fatty acid production in healthy individuals. Clinicians should recognize that high-dose B12 supplementation is not necessarily more beneficial and may alter the microbiome's metabolic capacity; however, these associations require validation in interventional studies before changing clinical practice.
Observational cross-sectional study in healthy adults showing associations between dietary B12 and microbial function via metagenomic analysis, but lacking intervention design, clinical outcomes, or causal inference; findings require confirmation in prospective or interventional studies.
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The findings suggest that excessive dietary B12 supplementation (>8.51 µg/day) may paradoxically reduce microbial B12 biosynthesis capacity and lower fecal short-chain fatty acid production in healthy individuals. Clinicians should recognize that high-dose B12 supplementation is not necessarily more beneficial and may alter the microbiome's metabolic capacity; however, these associations require validation in interventional studies before changing clinical practice.
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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.
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