Identification of environmental factors that promote intestinal inflammation

Sanmarco, Liliana M.; Chao, Chun‐Cheih; Wang, Yu Chao; Kenison, Jessica E.; Li, Zhaorong; Rone, Joseph M; Rejano-Gordillo, Claudia M.; Polonio, Carolina Manganeli; Gutiérrez-Vázquez, Cristina; Piester, Gavin; Plasencia, Agustín; Li, Lucinda; Giovannoni, Federico; Lee, Hong-Gyun; Akl, Camilo Faust; Wheeler, Michael A.; Mascanfroni, Iván; Jaronen, Merja; Alsuwailm, Moneera; Hewson, Patrick; Yeste, Ada; Andersen, Brian M.; Franks, Diana G.; Huang, Chien-Jung; Ekwudo, Millicent N.; Tjon, Emily; Rothhammer, Veit; Takenaka, Maisa C.; Lima, Kalil Alves de; Linnerbauer, Mathias; Guo, Lankai; Covacu, Ruxandra; Queva, Hugo; Fonseca-Castro, Pedro Henrique; Bladi, Maha Al; Cox, Laura M.; Hodgetts, Kevin J.; Hahn, Mark E.; Mildner, Alexander; Korzenik, Joshua R.; Hauser, Russ; Snapper, Scott B.; Quintana, Francisco J.

doi:10.1038/s41586-022-05308-6

Cited by 57 publications

(34 citation statements)

References 89 publications

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“…During his keynote speech, Francisco Quintana from Harvard Medical School, Boston, MA, USA, demonstrated the significance of using integrated systems approaches to discover new factors that contribute to inflammatory bowel disease (IBD) [ 11 ]. His team employed a wide range of experimental techniques, including public database mining, animal models, single-cell RNA sequencing, microbiome analysis, and large-scale chemical screening.…”

Section: Sessions and Presentationsmentioning

confidence: 99%

The Ah Receptor from Toxicity to Therapeutics: Report from the 5th AHR Meeting at Penn State University, USA, June 2022

Perdew

Esser

Snyder

et al. 2023

IJMS

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The aryl hydrocarbon receptor (AHR) is a sensor of low-molecular-weight molecule signals that originate from environmental exposures, the microbiome, and host metabolism. Building upon initial studies examining anthropogenic chemical exposures, the list of AHR ligands of microbial, diet, and host metabolism origin continues to grow and has provided important clues as to the function of this enigmatic receptor. The AHR has now been shown to be directly involved in numerous biochemical pathways that influence host homeostasis, chronic disease development, and responses to toxic insults. As this field of study has continued to grow, it has become apparent that the AHR is an important novel target for cancer, metabolic diseases, skin conditions, and autoimmune disease. This meeting attempted to cover the scope of basic and applied research being performed to address possible applications of our basic knowledge of this receptor on therapeutic outcomes.

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Section: Sessions and Presentationsmentioning

confidence: 99%

The Ah Receptor from Toxicity to Therapeutics: Report from the 5th AHR Meeting at Penn State University, USA, June 2022

Perdew

Esser

Snyder

et al. 2023

IJMS

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“…The developing central nervous system is particularly sensitive to environmental insults and chemical exposures can be especially harmful to children if they occur during critical periods of development 1,2 . For example, the heavy metals methylmercury and lead, as well as industrial chemicals such as polychlorinated biphenyls are known to disrupt brain development 3,4 .Chemical exposures may trigger pathogenesis or exacerbate underlying genetic factors [7][8][9] . Importantly, the prevalence of neurodevelopmental disorders including autism spectrum disorder and attentiondeficit hyperactivity has increased 10,11 , however, genetic factors can account for less than half of cases 2 .…”

Section: Mainmentioning

confidence: 99%

Pervasive environmental chemicals impair oligodendrocyte development

Cohn

Clayton

Madhavan

et al. 2023

Preprint

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Exposure to environmental chemicals can impair neurodevelopment. Oligodendrocytes that wrap around axons to boost neurotransmission may be particularly vulnerable to chemical toxicity as they develop throughout fetal development and into adulthood. However, few environmental chemicals have been assessed for potential risks to oligodendrocyte development. Here, we utilized a high-throughput developmental screen and human cortical brain organoids, which revealed environmental chemicals in two classes that disrupt oligodendrocyte development through distinct mechanisms. Quaternary compounds, ubiquitous in disinfecting agents, hair conditioners, and fabric softeners, were potently and selectively cytotoxic to developing oligodendrocytes through activation of the integrated stress response. Organophosphate flame retardants, commonly found in household items such as furniture and electronics, were non-cytotoxic but prematurely arrested oligodendrocyte maturation. Chemicals from each class impaired human oligodendrocyte development in a 3D organoid model of prenatal cortical development. In analysis of epidemiological data from the CDC's National Health and Nutrition Examination Survey, adverse neurodevelopmental outcomes were associated with childhood exposure to the top organophosphate flame retardant identified by our oligodendrocyte toxicity platform. Collectively, our work identifies toxicological vulnerabilities specific to oligodendrocyte development and highlights common household chemicals with high exposure risk to children that warrant deeper scrutiny for their impact on human health.

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“…Thereby, different liver characteristics have been described, including reduced size [ 119 ], collagen accumulation resulting in hepatic fibrosis [ 120 ], exacerbated proliferation of blood vessels [ 103 ] and lack of resolution of the portosystemic connection in adult mice [ 121 ]. Recently, the involvement of AHR in the control of hepatic energy and lipid metabolism and its relationship with metabolites from gut microbiome has been discovered [ 122 , 123 , 124 , 125 ]. Furthermore, AHR also regulates PI3K, ERK, and Wnt/β-Catenin signaling pathways, which are responsible for proliferation, differentiation and metabolism in the hepatic polyploidization process during liver maturation [ 61 ].…”

Section: Ahr Physiological Functionsmentioning

confidence: 99%

From Nucleus to Organs: Insights of Aryl Hydrocarbon Receptor Molecular Mechanisms

Rejano-Gordillo

Marín-Díaz

Ordiales-Talavero

et al. 2022

IJMS

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The aryl hydrocarbon receptor (AHR) is a markedly established regulator of a plethora of cellular and molecular processes. Its initial role in the detoxification of xenobiotic compounds has been partially overshadowed by its involvement in homeostatic and organ physiology processes. In fact, the discovery of its ability to bind specific target regulatory sequences has allowed for the understanding of how AHR modulates such processes. Thereby, AHR presents functions in transcriptional regulation, chromatin architecture modifications and participation in different key signaling pathways. Interestingly, such fields of influence end up affecting organ and tissue homeostasis, including regenerative response both to endogenous and exogenous stimuli. Therefore, from classical spheres such as canonical transcriptional regulation in embryonic development, cell migration, differentiation or tumor progression to modern approaches in epigenetics, senescence, immune system or microbiome, this review covers all aspects derived from the balance between regulation/deregulation of AHR and its physio-pathological consequences.

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Identification of environmental factors that promote intestinal inflammation

Cited by 57 publications

References 89 publications

The Ah Receptor from Toxicity to Therapeutics: Report from the 5th AHR Meeting at Penn State University, USA, June 2022

The Ah Receptor from Toxicity to Therapeutics: Report from the 5th AHR Meeting at Penn State University, USA, June 2022

Pervasive environmental chemicals impair oligodendrocyte development

From Nucleus to Organs: Insights of Aryl Hydrocarbon Receptor Molecular Mechanisms

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