title: Multi-Omics Reveals that Lead Exposure Disturbs Gut Microbiome Development, Key Metabolites, and Metabolic Pathways.
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 multiomics 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 the gut microbiome community structures/diversity but also greatly affected metabolic functions, leading to gut microbiome toxicity.
authors.affiliation: Department of Environmental Health Science, University of Georgia , Athens, Georgia 30602, United States.
authors.forename: Bei
authors.initials: B
authors.lastname: Gao
authors.affiliation: Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Liang
authors.initials: L
authors.lastname: Chi
authors.affiliation: Department of Environmental Health Science, University of Georgia , Athens, Georgia 30602, United States.
authors.forename: Ridwan
authors.initials: R
authors.lastname: Mahbub
authors.affiliation: Department of Environmental Health Science, University of Georgia , Athens, Georgia 30602, United States.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Bian
authors.affiliation: Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Tu
authors.affiliation: Department of Population Health and Pathobiology, North Carolina State University , Raleigh, North Carolina 27607, United States.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Ru
authors.affiliation: Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Kun
authors.identifier: 0000-0002-8125-2394
authors.initials: K
authors.lastname: Lu
mesh_terms: D000818:Animals; D001419:Bacteria / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D007854:Lead / Q000633:toxicity*; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D009572:Nitrite Reductases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D012336:RNA, Ribosomal, 16S / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014810:Vitamin E / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D012336:RNA, Ribosomal, 16S; C090404:UreE protein, Bacteria; D014810:Vitamin E; D007854:Lead; D009572:Nitrite Reductases