Feeding state greatly modulates the effect of xenobiotics on gut microbiome metabolism: a case study of tetracycline
The human gut microbiome is crucial in modulating host health mostly through bacterial metabolites. Chemical exposure is typical external stress which alters its composition and functionality. To date, very few studies have investigated the effect of feeding state on chemical-induced gut microbial m...
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sg-ntu-dr.10356-1602672022-07-18T07:42:34Z Feeding state greatly modulates the effect of xenobiotics on gut microbiome metabolism: a case study of tetracycline Keerthisinghe, Tharushi Prabha Yang, Qin Chow, Agnes Fang, Mingliang School of Civil and Environmental Engineering Lee Kong Chian School of Medicine (LKCMedicine) Nanyang Environment and Water Research Institute Singapore Phenome Centre Science::Medicine Tetracycline Gut Microbiome The human gut microbiome is crucial in modulating host health mostly through bacterial metabolites. Chemical exposure is typical external stress which alters its composition and functionality. To date, very few studies have investigated the effect of feeding state on chemical-induced gut microbial metabolic dysregulations. Here, we set up an in vitro human gut microbiome and incorporated a metabolomics approach to investigate the effect of tetracycline (TET) at multiple doses (i.e., 10, 1, and 0.01 mg/L) on gut microbiome under the fed and fasted states. Overall, the metabolome was highly responsive at the fed state with 62 metabolites dysregulated while only 14 were altered at the fasted state under 10 mg/L (clinical TET dose). As expected, nutrient consumption was significantly inhibited under clinical TET dose at the fed state accumulating nutrients such as glutamate and leucine. Interestingly, at the fed state, TET could increase the synthesis of indole and phenyl derivatives including indole-3-aldehyde and hydrocinnamate, while inhibiting indoxyl, tryptamine, and vitamin B production, all of which have host health implications. Furthermore, metabolites like indoxyl and xanthurenic acid were still responsive at 0.01 mg/L (dietary TET dose). Collectively, results demonstrated that the feeding state greatly modulates the chemical-induced gut microbial metabolic alterations. Ministry of Education (MOE) Ministry of Health (MOH) Nanyang Technological University National Environmental Agency (NEA) National Medical Research Council (NMRC) This work was funded by the Singapore Ministry of Education Academic Research Fund Tier 1 (04MNP000567C120EOM01), NTU-Harvard SusNano (M4082370.030), the Singapore National Environment Agency (M4061617), and Singapore Ministry of Health’s National Medical Research Council under its Clinician-Scientist Individual Research Grant (CS-IRG) (MOH-000141) and Open Fund – Individual Research Grant (OFIRG/0076/2018). 2022-07-18T07:42:34Z 2022-07-18T07:42:34Z 2021 Journal Article Keerthisinghe, T. P., Yang, Q., Chow, A. & Fang, M. (2021). Feeding state greatly modulates the effect of xenobiotics on gut microbiome metabolism: a case study of tetracycline. Journal of Hazardous Materials, 413, 125441-. https://dx.doi.org/10.1016/j.jhazmat.2021.125441 0304-3894 https://hdl.handle.net/10356/160267 10.1016/j.jhazmat.2021.125441 33930963 2-s2.0-85101166697 413 125441 en 04MNP000567C120EOM01 M4061617 MOH-000141 OFIRG/0076/2018 M4082370.030 Journal of Hazardous Materials © 2021 Elsevier B.V. All rights reserved. |
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Science::Medicine Tetracycline Gut Microbiome Keerthisinghe, Tharushi Prabha Yang, Qin Chow, Agnes Fang, Mingliang Feeding state greatly modulates the effect of xenobiotics on gut microbiome metabolism: a case study of tetracycline |
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The human gut microbiome is crucial in modulating host health mostly through bacterial metabolites. Chemical exposure is typical external stress which alters its composition and functionality. To date, very few studies have investigated the effect of feeding state on chemical-induced gut microbial metabolic dysregulations. Here, we set up an in vitro human gut microbiome and incorporated a metabolomics approach to investigate the effect of tetracycline (TET) at multiple doses (i.e., 10, 1, and 0.01 mg/L) on gut microbiome under the fed and fasted states. Overall, the metabolome was highly responsive at the fed state with 62 metabolites dysregulated while only 14 were altered at the fasted state under 10 mg/L (clinical TET dose). As expected, nutrient consumption was significantly inhibited under clinical TET dose at the fed state accumulating nutrients such as glutamate and leucine. Interestingly, at the fed state, TET could increase the synthesis of indole and phenyl derivatives including indole-3-aldehyde and hydrocinnamate, while inhibiting indoxyl, tryptamine, and vitamin B production, all of which have host health implications. Furthermore, metabolites like indoxyl and xanthurenic acid were still responsive at 0.01 mg/L (dietary TET dose). Collectively, results demonstrated that the feeding state greatly modulates the chemical-induced gut microbial metabolic alterations. |
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School of Civil and Environmental Engineering |
author_facet |
School of Civil and Environmental Engineering Keerthisinghe, Tharushi Prabha Yang, Qin Chow, Agnes Fang, Mingliang |
format |
Article |
author |
Keerthisinghe, Tharushi Prabha Yang, Qin Chow, Agnes Fang, Mingliang |
author_sort |
Keerthisinghe, Tharushi Prabha |
title |
Feeding state greatly modulates the effect of xenobiotics on gut microbiome metabolism: a case study of tetracycline |
title_short |
Feeding state greatly modulates the effect of xenobiotics on gut microbiome metabolism: a case study of tetracycline |
title_full |
Feeding state greatly modulates the effect of xenobiotics on gut microbiome metabolism: a case study of tetracycline |
title_fullStr |
Feeding state greatly modulates the effect of xenobiotics on gut microbiome metabolism: a case study of tetracycline |
title_full_unstemmed |
Feeding state greatly modulates the effect of xenobiotics on gut microbiome metabolism: a case study of tetracycline |
title_sort |
feeding state greatly modulates the effect of xenobiotics on gut microbiome metabolism: a case study of tetracycline |
publishDate |
2022 |
url |
https://hdl.handle.net/10356/160267 |
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1738844816899309568 |