Environmental Chemical Diethylhexyl Phthalate Alters Intestinal Microbiota Community Structure and Metabolite Profile in Mice

ABSTRACT Exposure to environmental chemicals during windows of development is a potentially contributing factor in gut microbiota dysbiosis and linked to chronic diseases and developmental disorders. We used a community-level model of microbiota metabolism to investigate the effects of diethylhexyl...

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Autores principales:	Ming Lei, Rani Menon, Sara Manteiga, Nicholas Alden, Carrie Hunt, Robert C. Alaniz, Kyongbum Lee, Arul Jayaraman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	autism metabolomics microbiota phthalates Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6d3aa32a54f84de1913a46b0d690bcfc
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spelling	oai:doaj.org-article:6d3aa32a54f84de1913a46b0d690bcfc2021-12-02T18:15:44ZEnvironmental Chemical Diethylhexyl Phthalate Alters Intestinal Microbiota Community Structure and Metabolite Profile in Mice10.1128/mSystems.00724-192379-5077https://doaj.org/article/6d3aa32a54f84de1913a46b0d690bcfc2019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00724-19https://doaj.org/toc/2379-5077ABSTRACT Exposure to environmental chemicals during windows of development is a potentially contributing factor in gut microbiota dysbiosis and linked to chronic diseases and developmental disorders. We used a community-level model of microbiota metabolism to investigate the effects of diethylhexyl phthalate (DEHP), a ubiquitous plasticizer implicated in neurodevelopmental disorders, on the composition and metabolite outputs of gut microbiota in young mice. Administration of DEHP by oral gavage increased the abundance of Lachnoclostridium, while decreasing Clostridium sensu stricto. Addition of DEHP to in vitro-cultured cecal microbiota increased the abundance of Paenibacillus and Lachnoclostridium. Untargeted metabolomics showed that DEHP broadly altered the metabolite profile in the culture. Notably, DEHP enhanced the production of p-cresol while inhibiting butyrate synthesis. Metabolic model-guided correlation analysis indicated that the likely sources of p-cresol are Clostridium species. Monoculture of Lachnoclostridium bolteae confirmed that it is capable of producing p-hydroxyphenylacetic acid, the immediate precursor of p-cresol, and that the species’ growth is enhanced upon DEHP exposure. Taken together, these findings suggest a model where DEHP increases production of p-cresol, a bacterial metabolite linked with neurodevelopmental disorders, by expanding the abundance of species that synthesize the metabolite’s precursor. IMPORTANCE Several previous studies have pointed to environmental chemical exposure during windows of development as a contributing factor in neurodevelopmental disorders and correlated these disorders with microbiota dysbiosis; however, little is known about how the chemicals specifically alter the microbiota to interfere with development. The findings reported in this paper unambiguously establish that a pollutant linked with neurodevelopmental disorders can directly modify the microbiota to promote the production of a potentially toxic metabolite (p-cresol) that has also been correlated with neurodevelopmental disorders. Furthermore, we used a novel modeling strategy to identify the responsible enzymes and bacterial sources of this metabolite. To the best of our knowledge, the present study is the first to characterize the functional consequence of phthalate exposure on a developed microbiota. Our results suggest that specific bacterial pathways could be developed as diagnostic and therapeutic targets against health risks posed by ingestion of environmental chemicals.Ming LeiRani MenonSara ManteigaNicholas AldenCarrie HuntRobert C. AlanizKyongbum LeeArul JayaramanAmerican Society for MicrobiologyarticleautismmetabolomicsmicrobiotaphthalatesMicrobiologyQR1-502ENmSystems, Vol 4, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	autism metabolomics microbiota phthalates Microbiology QR1-502
spellingShingle	autism metabolomics microbiota phthalates Microbiology QR1-502 Ming Lei Rani Menon Sara Manteiga Nicholas Alden Carrie Hunt Robert C. Alaniz Kyongbum Lee Arul Jayaraman Environmental Chemical Diethylhexyl Phthalate Alters Intestinal Microbiota Community Structure and Metabolite Profile in Mice
description	ABSTRACT Exposure to environmental chemicals during windows of development is a potentially contributing factor in gut microbiota dysbiosis and linked to chronic diseases and developmental disorders. We used a community-level model of microbiota metabolism to investigate the effects of diethylhexyl phthalate (DEHP), a ubiquitous plasticizer implicated in neurodevelopmental disorders, on the composition and metabolite outputs of gut microbiota in young mice. Administration of DEHP by oral gavage increased the abundance of Lachnoclostridium, while decreasing Clostridium sensu stricto. Addition of DEHP to in vitro-cultured cecal microbiota increased the abundance of Paenibacillus and Lachnoclostridium. Untargeted metabolomics showed that DEHP broadly altered the metabolite profile in the culture. Notably, DEHP enhanced the production of p-cresol while inhibiting butyrate synthesis. Metabolic model-guided correlation analysis indicated that the likely sources of p-cresol are Clostridium species. Monoculture of Lachnoclostridium bolteae confirmed that it is capable of producing p-hydroxyphenylacetic acid, the immediate precursor of p-cresol, and that the species’ growth is enhanced upon DEHP exposure. Taken together, these findings suggest a model where DEHP increases production of p-cresol, a bacterial metabolite linked with neurodevelopmental disorders, by expanding the abundance of species that synthesize the metabolite’s precursor. IMPORTANCE Several previous studies have pointed to environmental chemical exposure during windows of development as a contributing factor in neurodevelopmental disorders and correlated these disorders with microbiota dysbiosis; however, little is known about how the chemicals specifically alter the microbiota to interfere with development. The findings reported in this paper unambiguously establish that a pollutant linked with neurodevelopmental disorders can directly modify the microbiota to promote the production of a potentially toxic metabolite (p-cresol) that has also been correlated with neurodevelopmental disorders. Furthermore, we used a novel modeling strategy to identify the responsible enzymes and bacterial sources of this metabolite. To the best of our knowledge, the present study is the first to characterize the functional consequence of phthalate exposure on a developed microbiota. Our results suggest that specific bacterial pathways could be developed as diagnostic and therapeutic targets against health risks posed by ingestion of environmental chemicals.
format	article
author	Ming Lei Rani Menon Sara Manteiga Nicholas Alden Carrie Hunt Robert C. Alaniz Kyongbum Lee Arul Jayaraman
author_facet	Ming Lei Rani Menon Sara Manteiga Nicholas Alden Carrie Hunt Robert C. Alaniz Kyongbum Lee Arul Jayaraman
author_sort	Ming Lei
title	Environmental Chemical Diethylhexyl Phthalate Alters Intestinal Microbiota Community Structure and Metabolite Profile in Mice
title_short	Environmental Chemical Diethylhexyl Phthalate Alters Intestinal Microbiota Community Structure and Metabolite Profile in Mice
title_full	Environmental Chemical Diethylhexyl Phthalate Alters Intestinal Microbiota Community Structure and Metabolite Profile in Mice
title_fullStr	Environmental Chemical Diethylhexyl Phthalate Alters Intestinal Microbiota Community Structure and Metabolite Profile in Mice
title_full_unstemmed	Environmental Chemical Diethylhexyl Phthalate Alters Intestinal Microbiota Community Structure and Metabolite Profile in Mice
title_sort	environmental chemical diethylhexyl phthalate alters intestinal microbiota community structure and metabolite profile in mice
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/6d3aa32a54f84de1913a46b0d690bcfc
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Environmental Chemical Diethylhexyl Phthalate Alters Intestinal Microbiota Community Structure and Metabolite Profile in Mice

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