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Effects of Early Life Exposures to the Aryl Hydrocarbon Receptor Ligand TCDF on Gut Microbiota and Host Metabolic Homeostasis in C57BL/6J Mice.
Tian, Yuan; Rimal, Bipin; Bisanz, Jordan E; Gui, Wei; Wolfe, Trenton M; Koo, Imhoi; Murray, Iain A; Nettleford, Shaneice K; Yokoyama, Shigetoshi; Dong, Fangcong; Koshkin, Sergei; Prabhu, K Sandeep; Turnbaugh, Peter J; Walk, Seth T; Perdew, Gary H; Patterson, Andrew D.
Afiliación
  • Tian Y; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University (Penn State), University Park, Pennsylvania, USA.
  • Rimal B; Huck Institutes of the Life Sciences, Penn State, University Park, Pennsylvania, USA.
  • Bisanz JE; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University (Penn State), University Park, Pennsylvania, USA.
  • Gui W; Department of Biochemistry and Molecular Biology, Penn State, University Park, Pennsylvania, USA.
  • Wolfe TM; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, California, USA.
  • Koo I; Huck Institutes of the Life Sciences, Penn State, University Park, Pennsylvania, USA.
  • Murray IA; Department of Microbiology and Cell Biology, Montana State University, Bozeman, Montana, USA.
  • Nettleford SK; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University (Penn State), University Park, Pennsylvania, USA.
  • Yokoyama S; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University (Penn State), University Park, Pennsylvania, USA.
  • Dong F; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University (Penn State), University Park, Pennsylvania, USA.
  • Koshkin S; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University (Penn State), University Park, Pennsylvania, USA.
  • Prabhu KS; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University (Penn State), University Park, Pennsylvania, USA.
  • Turnbaugh PJ; Huck Institutes of the Life Sciences, Penn State, University Park, Pennsylvania, USA.
  • Walk ST; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University (Penn State), University Park, Pennsylvania, USA.
  • Perdew GH; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, California, USA.
  • Patterson AD; Chan Zuckerberg Biohub-San Francisco, San Francisco, California, USA.
Environ Health Perspect ; 132(8): 87005, 2024 Aug.
Article en En | MEDLINE | ID: mdl-39140734
ABSTRACT

BACKGROUND:

Exposure to persistent organic pollutants (POPs) and disruptions in the gastrointestinal microbiota have been positively correlated with a predisposition to factors such as obesity, metabolic syndrome, and type 2 diabetes; however, it is unclear how the microbiome contributes to this relationship.

OBJECTIVE:

This study aimed to explore the association between early life exposure to a potent aryl hydrocarbon receptor (AHR) agonist and persistent disruptions in the microbiota, leading to impaired metabolic homeostasis later in life.

METHODS:

This study used metagenomics, nuclear magnetic resonance (NMR)- and mass spectrometry (MS)-based metabolomics, and biochemical assays to analyze the gut microbiome composition and function, as well as the physiological and metabolic effects of early life exposure to 2,3,7,8-tetrachlorodibenzofuran (TCDF) in conventional, germ-free (GF), and Ahr-null mice. The impact of TCDF on Akkermansia muciniphila (A. muciniphila) in vitro was assessed using optical density (OD 600), flow cytometry, transcriptomics, and MS-based metabolomics.

RESULTS:

TCDF-exposed mice exhibited lower abundances of A. muciniphila, lower levels of cecal short-chain fatty acids (SCFAs) and indole-3-lactic acid (ILA), as well as lower levels of the gut hormones glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), findings suggestive of disruption in the gut microbiome community structure and function. Importantly, microbial and metabolic phenotypes associated with early life POP exposure were transferable to GF recipients in the absence of POP carry-over. In addition, AHR-independent interactions between POPs and the microbiota were observed, and they were significantly associated with growth, physiology, gene expression, and metabolic activity outcomes of A. muciniphila, supporting suppressed activity along the ILA pathway.

CONCLUSIONS:

These data obtained in a mouse model point to the complex effects of POPs on the host and microbiota, providing strong evidence that early life, short-term, and self-limiting POP exposure can adversely impact the microbiome, with effects persisting into later life with associated health implications. https//doi.org/10.1289/EHP13356.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Benzofuranos / Receptores de Hidrocarburo de Aril / Microbioma Gastrointestinal / Homeostasis / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Environ Health Perspect Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Benzofuranos / Receptores de Hidrocarburo de Aril / Microbioma Gastrointestinal / Homeostasis / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Environ Health Perspect Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos