The effects of micronutrient deficiencies on bacterial species from the human gut microbiota

Mechanistic studies reveal pronounced effects of vitamin A deficiency on bacterial members of a defined human gut microbiota. A gut bacterial view of micronutrient deficiency Deficiencies in vitamins and minerals (micronutrients) are a global health challenge. In a new study, Hibberd et al. compare the effects of acute dietary deficiency of vitamin A, folate, iron, or zinc in gnotobiotic mice harboring bacterial strains common in the human gut. Vitamin A had the greatest effect on the structure of the bacterial community and gene expression. Bacteroides vulgatus, a bacterial species positively correlated with host growth in gnotobiotic mouse models of postnatal human microbiota development, had the biggest response to vitamin A deficiency, exhibiting an increase in its abundance. Genetic, multi-omic, and pharmacologic analyses indicated that retinol treatment affected B. vulgatus fitness through the activity of the bacterial AcrAB-TolC efflux system. These results suggest that micronutrient imbalances should be considered from the perspective of both the human host and the gut microbiota they possess. Vitamin and mineral (micronutrient) deficiencies afflict 2 billion people. Although the impact of these imbalances on host biology has been studied extensively, much less is known about their effects on the gut microbiota of developing or adult humans. Therefore, we established a community of cultured, sequenced human gut–derived bacterial species in gnotobiotic mice and fed the animals a defined micronutrient-sufficient diet, followed by a derivative diet devoid of vitamin A, folate, iron, or zinc, followed by return to the sufficient diet. Acute vitamin A deficiency had the largest effect on bacterial community structure and metatranscriptome, with Bacteroides vulgatus, a prominent responder, increasing its abundance in the absence of vitamin A. Applying retinol selection to a library of 30,300 B. vulgatus transposon mutants revealed that disruption of acrR abrogated retinol sensitivity. Genetic complementation studies, microbial RNA sequencing, and transcription factor–binding assays disclosed that AcrR is a repressor of an adjacent AcrAB-TolC efflux system. Retinol efflux measurements in wild-type and acrR-mutant strains plus treatment with a pharmacologic inhibitor of the efflux system revealed that AcrAB-TolC is a determinant of retinol and bile acid sensitivity in B. vulgatus. Acute vitamin A deficiency was associated with altered bile acid metabolism in vivo, raising the possibility that retinol, bile acid metabolites, and AcrAB-TolC interact to influence the fitness of B. vulgatus and perhaps other microbiota members. This type of preclinical model can help to develop mechanistic insights about the effects of, and more effective treatment strategies for micronutrient deficiencies.