Dataset Information

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?

SUBMITTER: Wu J

PROVIDER: S-EPMC4880136 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Perinatal Lead Exposure Alters Gut Microbiota Composition and Results in Sex-specific Bodyweight Increases in Adult Mice.

Wu Jianfeng J Wen Xiaoquan William XW Faulk Christopher C Boehnke Kevin K Zhang Huapeng H Dolinoy Dana C DC Xi Chuanwu C

Toxicological sciences : an official journal of the Society of Toxicology 20160308 2

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 ...[more]

PMID: 26962054

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Project description:The mammalian intestinal tract is heavily colonized with a dense, complex, and diversified microbial populations. In healthy individuals, an array of epithelial antimicrobial agents is secreted in the gut to aid intestinal homeostasis. Enterochromaffin cells (EC) in the intestinal epithelium are a major source of chromogranin A (CgA), which is a pro-hormone and can be cleaved into many bioactive peptides that include catestatin (CST). This study was carried out to evaluate the possible impact of CST on gut microbiota in vivo using a mouse model. The CST (Human CgA352-372) or normal saline was intrarectally administered in C57BL/6 male mice for 6 days and then sacrificed. Feces and colonic mucosa tissue samples were collected, DNA was extracted, the V4 region of bacterial 16S rRNA gene was amplified and subjected to MiSeq Illumina sequencing. The ?-diversity was calculated using Chao 1 and ?-diversity was determined using QIIME. Differences at the genus level were determined using partial least square discriminant analysis (PLS-DA). Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was used to predict functional capacity of bacterial community. CST treatment did not modify bacterial richness in fecal and colonic mucosa-associated microbiota; however, treatment significantly modified bacterial community composition between the groups. Also, CST-treated mice had a significantly lower relative abundance of Firmicutes and higher abundance of Bacteroidetes, observed only in fecal samples. However, at lower phylogenetic levels, PLS-DA analysis revealed that some bacterial taxa were significantly associated with the CST-treated mice in both fecal and colonic mucosa samples. In addition, differences in predicted microbial functional pathways in both fecal and colonic mucosa samples were detected. The results support the hypothesis that CST treatment modulates gut microbiota composition under non-pathophysiological conditions, however, the result of this study needs to be further validated in a larger experiment. The data may open new avenues for the development of a potential new line of antimicrobial peptides and their use as therapeutic agents to treat several inflammatory conditions of the gastrointestinal tract, such as inflammatory bowel disease (IBD), inflammatory bowel syndrome (IBS), or other health conditions.

Project description:BackgroundLead (Pb) is a ubiquitous environmental contaminant with an array of detrimental health effects in children and adults, including neurological and immune dysfunction. Emerging evidence suggests that Pb exposure may alter the composition of the gut microbiota, however few studies have examined this association in human populations. The purpose of this study was to examine the association between urinary Pb concentration and the composition of the adult gut microbiota in a population-based sample of adults.MethodsData used in this study were collected as part of the Survey of the Health of Wisconsin (SHOW) and its ancillary microbiome study. The SHOW is a household-based health examination survey of Wisconsin residents, collecting a variety of survey data on health determinants and outcomes, as well as objective measurements of body habitus, and biological specimens including urine. The ancillary microbiome study added additional questions and biological specimen collection, including stool, from participants age 18+. Pb concentration was analyzed in urine samples, and gut microbiota composition was assessed using DNA sequencing of the 16S rRNA V4 region, extracted from stool samples. Data processing and statistical analyses were performed in mothur, Python, R, and SAS.ResultsOf 696 participants, urinary Pb concentration was highest in those age 70+, females, those with a high school diploma or lower, current and former smokers, and those without indoor pets. In adjusted models, increasing urinary Pb levels were associated with increases in microbial α-diversity (p = 0.071) and richness (p = 0.005). Differences in microbial β-diversity were significantly associated (p = 0.003) with differences in urinary Pb level. Presence of Proteobacteria, including members of the Burkholderiales, was significantly associated with increased urinary Pb.ConclusionThese results suggest that Pb exposure is associated with differences in the composition of the adult gut microbiota in a population-based human sample. Further investigation of this association is warranted.

Dataset Information

Perinatal Lead Exposure Alters Gut Microbiota Composition and Results in Sex-specific Bodyweight Increases in Adult Mice.

Publications

Perinatal Lead Exposure Alters Gut Microbiota Composition and Results in Sex-specific Bodyweight Increases in Adult Mice.

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