What is already known
Vitamin A, or retinol, and its derivative retinoic acid are essential for many biological processes including vision, growth, reproduction and immunity. Scientists have known that gut bacteria can complement the activity of mammalian enzymes in converting dietary vitamin A into retinoic acid, but it’s unclear whether gut bacteria could metabolize dietary vitamin A into active metabolites.
What this research adds
Using targeted metabolomics, researchers found that gut bacteria in the mouse gut produced a high concentration of vitamin A and its metabolites. Killing specific gut bacteria with antibiotics reduced vitamin A and its derivatives, whereas introducing these bacteria into germ-free mice boosted their production. Lactobacillus intestinalis metabolized vitamin A and restored the levels of retinoic acid in the gut of mice treated with antibiotics.
Conclusions
The results suggest that gut bacteria can regulate host physiology by metabolizing vitamin A. The findings may inform probiotic-based therapies with vitamin A derivatives, which are used to treat various conditions including inflammatory skin disorders, skin cancer and skin ageing.
Vitamin A, or retinol, and its derivative retinoic acid are essential for many biological processes including vision, growth, reproduction and immunity. New research done in mice suggests that gut bacteria can regulate host physiology by metabolizing vitamin A.
The findings, published in Cell Host & Microbe, may inform probiotic-based therapies with vitamin A derivatives, which are used to treat various conditions including inflammatory skin disorders, skin cancer and skin ageing.
Scientists have known that gut bacteria can complement the activity of mammalian enzymes in converting dietary vitamin A into retinoic acid. “However, [vitamin A] metabolic potential of gut bacterial community has not been evaluated using targeted metabolomic approaches that can quantify multiple [vitamin A] metabolites from a sample at the same time,” the researchers say.
To assess whether gut bacteria could metabolize dietary vitamin A into active metabolites, a team of researchers led by Nina Isoherrannen at the University of Washington and Shipra Vaishnava at Brown University used an approach that enriches for multiple retinoid species from the cecum of mice. Then, individual retinoids are identified and quantified by a technique called liquid chromatography-mass spectrometry, which separates mixtures of multiple components and provides spectral information that help to confirm the identity of each component.
Metabolizing vitamin A
Germ-free mice had substantially lower concentrations of active retinoids compared with conventional mice raised in the presence of microbes. Conventional mice treated with antibiotics to kill their gut flora also showed a drastic reduction of most vitamin A metabolites, the researchers found.
“Our data suggest that members of the gut microbiome have the metabolic potential to process dietary [vitamin A] into [retinol],” the researchers say.
To investigate which microbes possess this metabolic activity, the team treated mice with either vancomycin, which targets Clostridia and Bacteroidia, or neomycin, which targets Proteobacteria. Mice treated with vancomycin had lower levels of vitamin A derivatives in their guts compared to untreated mice. In contrast, treatment with neomycin did not appear to affect the levels of retinoids in the gut.
Restoring gut retinoids
Further experiments done in cells grown in a dish revealed that gut bacteria can metabolize dietary vitamin A independently of the host. Lactobacilli dominated the cultures in the presence of retinoids, the team found.
Some Lactobacilli such as Lactobacillus intestinalis have enzymes that allow them to metabolize vitamin A. Transferring L. intestinalis to the gut of mice treated with vancomycin restored the levels of retinoic acid and promoted the induction of retinoic-acid responsive genes.
More work is needed to determine exactly which bacteria are needed for vitamin A conversion into retinoic acid and their effects on the host, the researchers say. “Understanding how microbes communicate with their hosts via bacteria-sourced [retinoic acid] will provide opportunity to better describe how a host interacts with all microbes — beneficial, pathogenic, and commensal — and an opportunity to discover new ways to treat microbial-driven diseases,” they add.
