Cargando…

A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility

BACKGROUND: The composition of the bile acid (BA) pool is closely associated with obesity and is modified by gut microbiota. Perturbations of gut microbiota shape the BA composition, which, in turn, may alter important BA signaling and affect host metabolism. METHODS: We investigated BA composition...

Descripción completa

Detalles Bibliográficos
Autores principales: Wei, Meilin, Huang, Fengjie, Zhao, Ling, Zhang, Yunjing, Yang, Wei, Wang, Shouli, Li, Mengci, Han, Xiaolong, Ge, Kun, Qu, Chun, Rajani, Cynthia, Xie, Guoxiang, Zheng, Xiaojiao, Zhao, Aihua, Bian, Zhaoxiang, Jia, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225614/
https://www.ncbi.nlm.nih.gov/pubmed/32408110
http://dx.doi.org/10.1016/j.ebiom.2020.102766
_version_ 1783534107245936640
author Wei, Meilin
Huang, Fengjie
Zhao, Ling
Zhang, Yunjing
Yang, Wei
Wang, Shouli
Li, Mengci
Han, Xiaolong
Ge, Kun
Qu, Chun
Rajani, Cynthia
Xie, Guoxiang
Zheng, Xiaojiao
Zhao, Aihua
Bian, Zhaoxiang
Jia, Wei
author_facet Wei, Meilin
Huang, Fengjie
Zhao, Ling
Zhang, Yunjing
Yang, Wei
Wang, Shouli
Li, Mengci
Han, Xiaolong
Ge, Kun
Qu, Chun
Rajani, Cynthia
Xie, Guoxiang
Zheng, Xiaojiao
Zhao, Aihua
Bian, Zhaoxiang
Jia, Wei
author_sort Wei, Meilin
collection PubMed
description BACKGROUND: The composition of the bile acid (BA) pool is closely associated with obesity and is modified by gut microbiota. Perturbations of gut microbiota shape the BA composition, which, in turn, may alter important BA signaling and affect host metabolism. METHODS: We investigated BA composition of high BMI subjects from a human cohort study and a high fat diet (HFD) obesity prone (HF-OP) / HFD obesity resistant (HF-OR) mice model. Gut microbiota was analysed by metagenomics sequencing. GLP-1 secretion and gene regulation studies involved ELISA, qPCR, Western blot, Immunohistochemistry, and Immunofluorescence staining. FINDINGS: We found that the proportion of non-12-OH BAs was significantly decreased in the unhealthy high BMI subjects. The HF-OR mice had an enhanced level of non-12-OH BAs. Non-12-OH BAs including ursodeoxycholate (UDCA), chenodeoxycholate (CDCA), and lithocholate (LCA) were decreased in the HF-OP mice and associated with altered gut microbiota. Clostridium scindens was decreased in HF-OP mice and had a positive correlation with UDCA and LCA. Gavage of Clostridium scindens in mice increased the levels of hepatic non-12-OH BAs, accompanied by elevated serum 7α-hydroxy-4-cholesten-3-one (C4) levels. In HF-OP mice, altered BA composition was associated with significantly downregulated expression of GLP-1 in ileum and PGC1α, UCP1 in brown adipose tissue. In addition, we identified that UDCA attenuated the high fat diet-induced obesity via enhancing levels of non-12-OH BAs. INTERPRETATION: Our study highlights that dysregulated BA signaling mediated by gut microbiota contributes to obesity susceptibility, suggesting modulation of BAs could be a promising strategy for obesity therapy.
format Online
Article
Text
id pubmed-7225614
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-72256142020-05-18 A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility Wei, Meilin Huang, Fengjie Zhao, Ling Zhang, Yunjing Yang, Wei Wang, Shouli Li, Mengci Han, Xiaolong Ge, Kun Qu, Chun Rajani, Cynthia Xie, Guoxiang Zheng, Xiaojiao Zhao, Aihua Bian, Zhaoxiang Jia, Wei EBioMedicine Research paper BACKGROUND: The composition of the bile acid (BA) pool is closely associated with obesity and is modified by gut microbiota. Perturbations of gut microbiota shape the BA composition, which, in turn, may alter important BA signaling and affect host metabolism. METHODS: We investigated BA composition of high BMI subjects from a human cohort study and a high fat diet (HFD) obesity prone (HF-OP) / HFD obesity resistant (HF-OR) mice model. Gut microbiota was analysed by metagenomics sequencing. GLP-1 secretion and gene regulation studies involved ELISA, qPCR, Western blot, Immunohistochemistry, and Immunofluorescence staining. FINDINGS: We found that the proportion of non-12-OH BAs was significantly decreased in the unhealthy high BMI subjects. The HF-OR mice had an enhanced level of non-12-OH BAs. Non-12-OH BAs including ursodeoxycholate (UDCA), chenodeoxycholate (CDCA), and lithocholate (LCA) were decreased in the HF-OP mice and associated with altered gut microbiota. Clostridium scindens was decreased in HF-OP mice and had a positive correlation with UDCA and LCA. Gavage of Clostridium scindens in mice increased the levels of hepatic non-12-OH BAs, accompanied by elevated serum 7α-hydroxy-4-cholesten-3-one (C4) levels. In HF-OP mice, altered BA composition was associated with significantly downregulated expression of GLP-1 in ileum and PGC1α, UCP1 in brown adipose tissue. In addition, we identified that UDCA attenuated the high fat diet-induced obesity via enhancing levels of non-12-OH BAs. INTERPRETATION: Our study highlights that dysregulated BA signaling mediated by gut microbiota contributes to obesity susceptibility, suggesting modulation of BAs could be a promising strategy for obesity therapy. Elsevier 2020-05-11 /pmc/articles/PMC7225614/ /pubmed/32408110 http://dx.doi.org/10.1016/j.ebiom.2020.102766 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research paper
Wei, Meilin
Huang, Fengjie
Zhao, Ling
Zhang, Yunjing
Yang, Wei
Wang, Shouli
Li, Mengci
Han, Xiaolong
Ge, Kun
Qu, Chun
Rajani, Cynthia
Xie, Guoxiang
Zheng, Xiaojiao
Zhao, Aihua
Bian, Zhaoxiang
Jia, Wei
A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility
title A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility
title_full A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility
title_fullStr A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility
title_full_unstemmed A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility
title_short A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility
title_sort dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225614/
https://www.ncbi.nlm.nih.gov/pubmed/32408110
http://dx.doi.org/10.1016/j.ebiom.2020.102766
work_keys_str_mv AT weimeilin adysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT huangfengjie adysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT zhaoling adysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT zhangyunjing adysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT yangwei adysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT wangshouli adysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT limengci adysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT hanxiaolong adysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT gekun adysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT quchun adysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT rajanicynthia adysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT xieguoxiang adysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT zhengxiaojiao adysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT zhaoaihua adysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT bianzhaoxiang adysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT jiawei adysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT weimeilin dysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT huangfengjie dysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT zhaoling dysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT zhangyunjing dysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT yangwei dysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT wangshouli dysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT limengci dysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT hanxiaolong dysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT gekun dysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT quchun dysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT rajanicynthia dysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT xieguoxiang dysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT zhengxiaojiao dysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT zhaoaihua dysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT bianzhaoxiang dysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility
AT jiawei dysregulatedbileacidgutmicrobiotaaxiscontributestoobesitysusceptibility