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

Hibberd, Matthew C.; Wu, Meng; Rodionov, Dmitry A.; Li, Xiaoqing; Cheng, Jiye; Griffin, Nicholas W.; Barratt, Michael J.; Giannone, Richard J.; Hettich, Robert L.; Osterman, Andrei L.; Gordon, Jeffrey I.

doi:10.1126/scitranslmed.aal4069

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

Journal Article · Wed May 17 00:00:00 EDT 2017 · Science Translational Medicine

DOI:https://doi.org/10.1126/scitranslmed.aal4069· OSTI ID:1394231

^[1]; ^[2]; ^[3]; Li, Xiaoqing ^[4]; Cheng, Jiye ^[5]; ^[5]; ^[5]; ^[6]; ^[6]; Osterman, Andrei L. ^[4]; ^[5]

Washington Univ. School of Medicine, St. Louis, MO (United States). Center for Genome Sciences and Systems Biology, Center for Gut Microbiome and Nutrition Research
Washington Univ. School of Medicine, St. Louis, MO (United States). Center for Genome Sciences and Systems Biology
Russian Academy of Sciences (RAS), Moscow (Russian Federation). A.A. Kharkevich Inst. for Information Transmission Problems; Sanford Burnham Prebys Medical Discovery Inst., La Jolla, CA (United States)
Sanford Burnham Prebys Medical Discovery Inst., La Jolla, CA (United States)
Washington Univ. School of Medicine, St. Louis, MO (United States). Center for Genome Sciences and Systems Biology, Center for Gut Microbiome and Nutrition Researc
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Chemical Sciences Division

Micronutrient deficiencies afflict two billion people. And while the impact of these imbalances on host biology has been studied extensively, much less is known about their effects on the developing or adult gut microbiota. Thus, we established a community of 44 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 community structure and meta-transcriptome, with Bacteroides vulgatus, a prominent responder, increasing its abundance in the absence of vitamin A, and manifesting transcriptional changes involving various metabolic pathways. 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-Seq, and transcription factor binding assays disclosed that AcrR functions as a repressor of an adjacent AcrAB-TolC efflux system plus other members of its regulon. Retinol efflux measurements in wild-type, acrR-mutant, and complemented 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. We associated acute vitamin A deficiency 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 develop mechanistic insights about and more effective treatment strategies for micronutrient deficiencies.

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE

DOE Contract Number:: AC05-00OR22725

OSTI ID:: 1394231

Journal Information:: Science Translational Medicine, Journal Name: Science Translational Medicine Journal Issue: 390 Vol. 9; ISSN 1946-6234

Publisher:: AAAS

Country of Publication:: United States

Language:: English

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