Temporal Development of Gut Microbiota in Triclocarban Exposed Pregnant and Neonatal Rats

Kennedy, Rebekah C.; Fling, Russell R.; Robeson, Michael S.; Saxton, Arnold M.; Donnell, Robert; Darcy, John L.; Bemis, David A.; Liu, Jiang; Zhao, Ling; Chen, Jiangang

doi:10.1038/srep33430

Cited by 26 publications

(20 citation statements)

References 53 publications

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“…Adolescent rats receiving oral triclosan at levels comparable to human exposures develop lower microbial diversity in the gut and more prominent changes in taxonomic composition than in adult rats (Hu et al , ). While triclocarban exposures are less studied, in pregnant rats and their offspring < 10 days old exposure leads to lowered phylogenetic diversity and revealed a dominance of the Proteobacteria phylum in the gut (Kennedy et al , ). In a small, randomized, crossover human study, TC wash product exposure did not induce major perturbations of the oral and gut microbiomes (Poole et al , ).…”

Section: Introductionmentioning

confidence: 99%

Household triclosan and triclocarban effects on the infant and maternal microbiome

et al. 2017

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In 2016, the US Food and Drug Administration banned the use of specific microbicides in some household and personal wash products due to concerns that these chemicals might induce antibiotic resistance or disrupt human microbial communities. Triclosan and triclocarban (referred to as TCs) are the most common antimicrobials in household and personal care products, but the extent to which TC exposure perturbs microbial communities in humans, particularly during infant development, was unknown. We conducted a randomized intervention of TC‐containing household and personal care products during the first year following birth to characterize whether TC exposure from wash products perturbs microbial communities in mothers and their infants. Longitudinal survey of the gut microbiota using 16S ribosomal RNA amplicon sequencing showed that TC exposure from wash products did not induce global reconstruction or loss of microbial diversity of either infant or maternal gut microbiotas. Broadly antibiotic‐resistant species from the phylum Proteobacteria, however, were enriched in stool samples from mothers in TC households after the introduction of triclosan‐containing toothpaste. When compared by urinary triclosan level, agnostic to treatment arm, infants with higher triclosan levels also showed an enrichment of Proteobacteria species. Despite the minimal effects of TC exposure from wash products on the gut microbial community of infants and adults, detected taxonomic differences highlight the need for consumer safety testing of antimicrobial self‐care products on the human microbiome and on antibiotic resistance.

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Section: Introductionmentioning

confidence: 99%

Household triclosan and triclocarban effects on the infant and maternal microbiome

et al. 2017

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“…Previous reports have demonstrated that exposure to TCC results in adverse effects on the gastrointestinal tract of neonate mice. Acute gastric ulcers and dysbiosis of gut microbiota have been observed in neonate mice directly or indirectly absorbing TCC during pregnancy or lactation . In human intestinal epithelial cell lines, ER stress is triggered, and apoptosis is induced by 4‐NP, a common contaminant in environment .…”

Section: Discussionmentioning

confidence: 99%

Triclocarban at environmentally relevant concentrations induces the endoplasmic reticulum stress in zebrafish

Zhou

Wei

et al. 2018

Environmental Toxicology

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Triclocarban (TCC) is an antibacterial agent commonly found in environmental, wildlife, and human samples. However, with in-depth study of TCC, its negative effects are increasingly presented.Toxicological studies of TCC at environmentally relevant concentrations have been conducted in zebrafish embryos and indicated that TCC leads to deformity of development causes developmental deformities. However, the molecular mechanisms underlying the toxicity of TCC in zebrafish embryos have not been entirely elucidated. We investigated whether exposure to TCC at environmentally relevant concentrations induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in zebrafish. Zebrafish embryos were grown to 32 hours post fertilization and exposed to 2.5, 5, and 10 μg/L TCC and used in whole-mount in situ hybridization to visualize the expression of ER chaperone hspa5 and ER stress-related apoptosis factor chop. Zebrafish livers were exposed to different concentrations of TCC to elaborate the relationships between fatty degeneration and ER stress. Then, a human hepatic cell line (HL-7702) was used to test whether TCC induced ER stress in human livers similar to those of zebrafish. In zebrafish embryos, TCC induced high hspa5 expression, which could defend against external stimulations. Furthermore, hapa5, hsp90b1, and chop exhibited ectopic expressions in the neuromast, intestinal tract, and tail tip of zebrafish embryos. On the one hand, significant differences were observed in the mRNA and protein expressions of the ER stress molecular chaperone pPERK-pEIF2a-ATF4 and ATF6 pathways in HL-7702 cells exposed to TCC. On the other hand, lipid droplet accumulation slightly increased in zebrafish livers exposed to 10 μg/L TCC in vitro. These results demonstrate that TCC not only damages the development of zebrafish embryos and structure of zebrafish liver but also influences human hepatic cells by activating ER stress and the UPR signaling pathway. K E Y W O R D S endoplasmic reticulum stress, HL-7702, triclocarban, unfolded protein response, zebrafish embryos

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“…There is a complex relationship among the maternal, nutritional, and developmental events that surround the seeding of the neonatal microbiome (Miller, 2016;Ganal-Vonarburg et al, 2017). These events have also been evaluated to some extent in neonates of nonclinical species, including the rat (Kennedy et al, 2016;Ganal-Vonarburg et al, 2017), dog (Guard et al, 2017), pig (Saraf et al, 2017), and rhesus macaque (Ardeshir et al, 2014).…”

Section: Neonatal Microbiomementioning

confidence: 99%

“…When considering the ADME characteristics of the neonatal gastrointestinal system, it is important to also consider the potential role of the neonatal microbiome. This is especially important given the relatively high risk of infection in neonates, the current use of peripartum antimicrobial agents in mothers and neonates, and the potential role of microbiota in the metabolism of both nutrients and medicines (Sherman et al, 2014;Kennedy et al, 2016;Macpherson et al, 2017;Nogacka et al, 2017).…”

Section: Neonatal Microbiomementioning

confidence: 99%

Physiology of the Neonatal Gastrointestinal System Relevant to the Disposition of Orally Administered Medications

et al. 2018

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A thorough knowledge of the newborn (age, birth to 1 month postpartum) infant's gastrointestinal tract (GIT) is critical to the evaluation of the absorption, distribution, metabolism, and excretion (ADME) of orally administered drugs in this population. Developmental changes in the GIT during the newborn period are important for nutrient uptake as well as the disposition of orally administered medications. Some aspects of gastrointestinal function do not mature until driven by increased dietary complexity and nutritional demands later in the postnatal period. The functionalities present at birth, and subsequent maturation, can also impact the ADME parameters of orally administered compounds. This review will examine some specific contributors to the ADME processes in human neonates, as well as what is currently understood about the drivers for their maturation. Key species differences will be highlighted, with a focus on laboratory animals used in juvenile toxicity studies. Because of the gaps and inconsistencies in our knowledge, we will also highlight areas where additional study is warranted to better inform the appropriate use of medicines specifically intended for neonates.

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Temporal Development of Gut Microbiota in Triclocarban Exposed Pregnant and Neonatal Rats

Cited by 26 publications

References 53 publications

Household triclosan and triclocarban effects on the infant and maternal microbiome

Household triclosan and triclocarban effects on the infant and maternal microbiome

Triclocarban at environmentally relevant concentrations induces the endoplasmic reticulum stress in zebrafish

Physiology of the Neonatal Gastrointestinal System Relevant to the Disposition of Orally Administered Medications

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