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      Multi-Omics Reveals that Lead Exposure Disturbs Gut Microbiome Development, Key Metabolites and Metabolic Pathways

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          Abstract

          Lead exposure remains a global public health issue, and the recent Flint water crisis has renewed public concern about lead toxicity. The toxicity of lead has been well established in a variety of systems and organs. The gut microbiome has been shown to be highly involved in many critical physiological processes, including food digestion, immune system development and metabolic homeostasis. However, despite the key role of the gut microbiome in human health, the functional impact of lead exposure on the gut microbiome has not been studied. The aim of this study is to define gut microbiome toxicity induced by lead exposure in C57BL/6 mice using multi-omics approaches, including 16S rRNA sequencing, whole genome metagenomics sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics. 16S rRNA sequencing revealed that lead exposure altered the gut microbiome trajectory and phylogenetic diversity. Metagenomics sequencing and metabolomics profiling showed that numerous metabolic pathways, including vitamin E, bile acids, nitrogen metabolism, energy metabolism, oxidative stress and the defense/detoxification mechanism, were significantly disturbed by lead exposure. These perturbed molecules and pathways may have important implications for lead toxicity in the host. Taken together, these results demonstrated that lead exposure not only altered gut microbiome community structures/diversity but also greatly affected metabolic functions, leading to gut microbiome toxicity.

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          Author and article information

          Journal
          8807448
          1179
          Chem Res Toxicol
          Chem. Res. Toxicol.
          Chemical research in toxicology
          0893-228X
          1520-5010
          13 October 2017
          16 March 2017
          17 April 2017
          24 October 2017
          : 30
          : 4
          : 996-1005
          Affiliations
          []Department of Environmental Health Science, University of Georgia, Athens, GA, 30602
          []Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599
          [§ ]Department of Population Health and Pathobiology, North Carolina State University, Raleigh, NC, 27607
          Author notes
          [* ]Corresponding Authors: Kun Lu, PhD, Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, Tel.: 919 966 7337, kunlu@ 123456unc.edu
          Article
          PMC5654721 PMC5654721 5654721 nihpa912416
          10.1021/acs.chemrestox.6b00401
          5654721
          28234468
          7dfd72bf-a311-4955-a684-b61e2cca61dd
          History
          Categories
          Article

          metabolic functions,gut microbiome toxicity,omics,lead
          metabolic functions, gut microbiome toxicity, omics, lead

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