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Gut Microbiota-Mediated Elevated Production of Secondary Bile Acids in Chronic Unpredictable Mild Stress

A growing body of evidence suggests that gut microbiota could participate in the progression of depression via the microbiota–gut–brain axis. However, the detailed microbial metabolic profile changes in the progression of depression is still not fully elucidated. In this study, a liquid chromatograp...

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Autores principales: Qu, Yuchen, Su, Cunjin, Zhao, Qinhong, Shi, Aiming, Zhao, Fenglun, Tang, Liuxing, Xu, Delai, Xiang, Zheng, Wang, Yang, Wang, Yueyuan, Pan, Jie, Yu, Yunli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8936594/
https://www.ncbi.nlm.nih.gov/pubmed/35321330
http://dx.doi.org/10.3389/fphar.2022.837543
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author Qu, Yuchen
Su, Cunjin
Zhao, Qinhong
Shi, Aiming
Zhao, Fenglun
Tang, Liuxing
Xu, Delai
Xiang, Zheng
Wang, Yang
Wang, Yueyuan
Pan, Jie
Yu, Yunli
author_facet Qu, Yuchen
Su, Cunjin
Zhao, Qinhong
Shi, Aiming
Zhao, Fenglun
Tang, Liuxing
Xu, Delai
Xiang, Zheng
Wang, Yang
Wang, Yueyuan
Pan, Jie
Yu, Yunli
author_sort Qu, Yuchen
collection PubMed
description A growing body of evidence suggests that gut microbiota could participate in the progression of depression via the microbiota–gut–brain axis. However, the detailed microbial metabolic profile changes in the progression of depression is still not fully elucidated. In this study, a liquid chromatography coupled to mass spectrometry-based untargeted serum high-throughput metabolomics method was first performed to screen for potential biomarkers in a depressive-like state in a chronic unpredictable mild stress (CUMS)-induced mouse model. Our results identified that the bile acid and energy metabolism pathways were significantly affected in CUMS progression. The detailed bile acid profiles were subsequently quantified in the serum, liver, and feces. The results showed that CUMS significantly promoted the deconjugation of conjugated bile acid and secondary bile acid biosynthesis. Furthermore, 16S rRNA gene sequencing revealed that the increased secondary bile acid levels in the feces positively correlated with Ruminococcaceae_UCG-010, Ruminococcus, and Clostridia_UCG-014 abundance. Taken together, our study suggested that changes in family Ruminococcaceae abundance following chronic stress increased biosynthesis of deoxycholic acid (DCA), a unconjugated secondary bile acid in the intestine. Aberrant activation of secondary bile acid biosynthesis pathway thereby increased the hydrophobicity of the bile acid pool, which might, in turn, promoted metabolic disturbances and disease progression in CUMS mice.
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spelling pubmed-89365942022-03-22 Gut Microbiota-Mediated Elevated Production of Secondary Bile Acids in Chronic Unpredictable Mild Stress Qu, Yuchen Su, Cunjin Zhao, Qinhong Shi, Aiming Zhao, Fenglun Tang, Liuxing Xu, Delai Xiang, Zheng Wang, Yang Wang, Yueyuan Pan, Jie Yu, Yunli Front Pharmacol Pharmacology A growing body of evidence suggests that gut microbiota could participate in the progression of depression via the microbiota–gut–brain axis. However, the detailed microbial metabolic profile changes in the progression of depression is still not fully elucidated. In this study, a liquid chromatography coupled to mass spectrometry-based untargeted serum high-throughput metabolomics method was first performed to screen for potential biomarkers in a depressive-like state in a chronic unpredictable mild stress (CUMS)-induced mouse model. Our results identified that the bile acid and energy metabolism pathways were significantly affected in CUMS progression. The detailed bile acid profiles were subsequently quantified in the serum, liver, and feces. The results showed that CUMS significantly promoted the deconjugation of conjugated bile acid and secondary bile acid biosynthesis. Furthermore, 16S rRNA gene sequencing revealed that the increased secondary bile acid levels in the feces positively correlated with Ruminococcaceae_UCG-010, Ruminococcus, and Clostridia_UCG-014 abundance. Taken together, our study suggested that changes in family Ruminococcaceae abundance following chronic stress increased biosynthesis of deoxycholic acid (DCA), a unconjugated secondary bile acid in the intestine. Aberrant activation of secondary bile acid biosynthesis pathway thereby increased the hydrophobicity of the bile acid pool, which might, in turn, promoted metabolic disturbances and disease progression in CUMS mice. Frontiers Media S.A. 2022-03-07 /pmc/articles/PMC8936594/ /pubmed/35321330 http://dx.doi.org/10.3389/fphar.2022.837543 Text en Copyright © 2022 Qu, Su, Zhao, Shi, Zhao, Tang, Xu, Xiang, Wang, Wang, Pan and Yu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Qu, Yuchen
Su, Cunjin
Zhao, Qinhong
Shi, Aiming
Zhao, Fenglun
Tang, Liuxing
Xu, Delai
Xiang, Zheng
Wang, Yang
Wang, Yueyuan
Pan, Jie
Yu, Yunli
Gut Microbiota-Mediated Elevated Production of Secondary Bile Acids in Chronic Unpredictable Mild Stress
title Gut Microbiota-Mediated Elevated Production of Secondary Bile Acids in Chronic Unpredictable Mild Stress
title_full Gut Microbiota-Mediated Elevated Production of Secondary Bile Acids in Chronic Unpredictable Mild Stress
title_fullStr Gut Microbiota-Mediated Elevated Production of Secondary Bile Acids in Chronic Unpredictable Mild Stress
title_full_unstemmed Gut Microbiota-Mediated Elevated Production of Secondary Bile Acids in Chronic Unpredictable Mild Stress
title_short Gut Microbiota-Mediated Elevated Production of Secondary Bile Acids in Chronic Unpredictable Mild Stress
title_sort gut microbiota-mediated elevated production of secondary bile acids in chronic unpredictable mild stress
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8936594/
https://www.ncbi.nlm.nih.gov/pubmed/35321330
http://dx.doi.org/10.3389/fphar.2022.837543
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