title: Perinatal Lead Exposure Alters Gut Microbiota Composition and Results in Sex-specific Bodyweight Increases in Adult Mice.
abstract: Heavy metal pollution is a principle source of environmental contamination. Epidemiological and animal data suggest that early life lead (Pb) exposure results in critical effects on epigenetic gene regulation and child and adult weight trajectories. Using a mouse model of human-relevant exposure, we investigated the effects of perinatal Pb exposure on gut microbiota in adult mice, and the link between gut microbiota and bodyweight changes. Following Pb exposure during gestation and lactation via maternal drinking water, bodyweight in A(vy) strain wild-type non-agouti (a/a) offspring was tracked through adulthood. Gut microbiota of adult mice were characterized by deep DNA sequencing of bacterial 16S ribosomal RNA genes. Data analyses were stratified by sex and adjusted for litter effects. A Bayesian variable selection algorithm was used to analyze associations between bacterial operational taxonomic units and offspring adult bodyweight. Perinatal Pb exposure was associated with increased adult bodyweight in male (P < .05) but not in female offspring (P = .24). Cultivable aerobes decreased and anaerobes increased in Pb-exposed offspring (P < .005 and P < .05, respectively). Proportions of the 2 predominant phyla (Bacteroidetes and Firmicutes) shifted inversely with Pb exposure, and whole bacterial compositions were significantly different (analysis of molecular variance, P < .05) by Pb exposure without sex bias. In males, changes in gut microbiota were highly associated with adult bodyweight (P = .028; effect size = 2.59). Thus, perinatal Pb exposure results in altered adult gut microbiota regardless of sex, and these changes are highly correlated with increased bodyweight in males. Adult gut microbiota can be shaped by early exposures and may contribute to disease risks in a sex-specific manner.
authors.affiliation: *Department of Environmental Health Sciences.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Biostatistics.
authors.forename: Xiaoquan William
authors.initials: XW
authors.lastname: Wen
authors.affiliation: *Department of Environmental Health Sciences.
authors.forename: Christopher
authors.initials: C
authors.lastname: Faulk
authors.affiliation: *Department of Environmental Health Sciences.
authors.forename: Kevin
authors.initials: K
authors.lastname: Boehnke
authors.affiliation: *Department of Environmental Health Sciences.
authors.forename: Huapeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: *Department of Environmental Health Sciences Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Dolinoy
authors.affiliation: *Department of Environmental Health Sciences cxi@umich.edu.
authors.forename: Chuanwu
authors.initials: C
authors.lastname: Xi
mesh_terms: D000367:Age Factors; D000818:Animals; D001419:Bacteria / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000382:microbiology; D005865:Gestational Age; D007774:Lactation; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D009942:Organometallic Compounds / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D021521:Ribotyping; D012737:Sex Factors; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D009942:Organometallic Compounds; D014874:Water Pollutants, Chemical; C008261:lead acetate
keywords: Bacteroidetes and Firmicutes; bodyweight; gut microbiota; microbiom; perinatal lead (Pb) exposure