“Our results reveal sex differences and age-related trends in microbial vitamin production and identify associations between gut microbial vitamin pathways and health-related factors, as well as medical and dietary factors that influence gut microbial vitamin production, suggesting the value of microbiome-targeted interventions to adjust intrinsic vitamin production and improve wellbeing,” wrote scientists from the University of Groningen in the Netherlands and the DSM Nutritional Products R&D center in Switzerland.
Funded by life sciences multinational Royal DSM, the study draws from LifeLines, a large population-based prospective cohort study that enrolled 167,729 participants between the ages 6 months to 93 years from the northern Netherlands to explore the risk factors behind complex diseases.
Vitamin supply and diabetes
Noting that vitamin biosynthesis genes and pathways have been discovered in many common gut bacterial species, the researchers point to evidence that diabetes patients often have abnormal vitamin levels, including vitamin D deficiency and abnormal urinary loss of vitamin C.
Higher levels of folate and vitamin B12 in red blood cells during early pregnancy have also been associated with a higher risk of gestational diabetes, while long-term use of anti-diabetic medication metformin has been found to induce vitamin B12 deficiency, leading to hematologic abnormalities, progressive axonal demyelination and peripheral neuropathy.
“Maintaining a healthy vitamin supply in the body is thus a crucial element of diabetes prevention and treatment,” the researchers noted. “Beside the external intake of vitamins through diet and supplements, another important source of vitamins is intrinsic vitamin production by the gut microbiome.”
They added that this is the first study to comprehensively evaluate the relationship between gut microbial vitamin production, diabetes and cardiometabolic health–related and exposure factors.
Study details
The study examined high-quality metagenomic sequencing data, 78 dietary factors, 5 smoking factors and 44 drug usage factors in 1,135 adults drawn from the LifeLines cohort, including 474 men and 661 women with an average age of 45 years.
To assess the hypothesis that “inter-individual variation in bacterial vitamin production capacity in the gut microbiome may impact human health”, the research team extracted the abundance levels of 28 vitamin biosynthesis pathways from the metagenomics data. These pathways involved the production of vitamin Bs (B1, B2, B5, B6, B7/B8/H, B9, and B12) and one vitamin C pathway. A linear model that included age and sex as covariates was then used to analyze 58 health-related factors, identifying 54 positive and 145 negative associations with bacterial vitamin pathways for 26 of these factors.
“We found that blood glucose–related factors, lipids, circulating inflammation and fecal short-chain fatty acids are associated with gut microbial vitamin production,” the researchers concluded.
“Use of laxatives and metformin are associated with increased levels of vitamin B1/B6 biosynthesis pathways. We further reveal a mediatory role for microbial vitamin B1/B2 production on the influence of fruit intake on diabetes risk.”
They also found that abundance levels of total bacterial vitamin biosynthesis pathways of B6 and B2 were higher in females than males, whereas B12 biosynthesis was enriched in males. The abundance of gut microbial B12 production pathways also decreased in middle-aged and older participants, indicating a correlation between age-related microbiome alteration and vitamin levels.
For future study, the researchers suggest further evaluation of proton pump inhibitors or laxatives as potential microbiome-targeted drugs for vitamin metabolism intervention, replication of the study in non-Dutch populations and investigation of the impact of host genetic factors on vitamin absorption.
Source: Gut Microbes
doi: 10.1080/19490976.2022.2154550
“Microbial vitamin production mediates dietary effects on diabetic risk”
Authors: Daoming Wang et al.