Cargando…
Chaihu-shugan-san alleviates depression-like behavior in mice exposed to chronic unpredictable stress by altering the gut microbiota and levels of the bile acids hyocholic acid and 7-ketoDCA
Chaihu-Shugan-San (CSS) is a traditional botanical drug formula often prescribed to treat depression in oriental countries, but its pharmacotherapeutic mechanism remains unknown. It was recently reported that CSS alters the composition of intestinal microflora and related metabolites such as bile ac...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9627339/ https://www.ncbi.nlm.nih.gov/pubmed/36339629 http://dx.doi.org/10.3389/fphar.2022.1040591 |
_version_ | 1784822945426702336 |
---|---|
author | Ma, Chong Yuan, Dun Renaud, Stephen James Zhou, Ting Yang, Fan Liou, Yuligh Qiu, Xinjian Zhou, Lu Guo, Ying |
author_facet | Ma, Chong Yuan, Dun Renaud, Stephen James Zhou, Ting Yang, Fan Liou, Yuligh Qiu, Xinjian Zhou, Lu Guo, Ying |
author_sort | Ma, Chong |
collection | PubMed |
description | Chaihu-Shugan-San (CSS) is a traditional botanical drug formula often prescribed to treat depression in oriental countries, but its pharmacotherapeutic mechanism remains unknown. It was recently reported that CSS alters the composition of intestinal microflora and related metabolites such as bile acids (BAs). Since the intestinal microflora affects physiological functions of the brain through the gut-microbiota-brain axis, herein we investigated whether CSS altered BA levels, gut microflora, and depression-like symptoms in chronic unpredictable mild stress (CUMS) mice, a well-established mouse model of depression. Furthermore, we determined whether BA manipulation and fecal microbiota transplantation altered CSS antidepressant actions. We found that the BA chelator cholestyramine impaired the antidepressant effects of CSS, which was partially rescued by dietary cholic acid. CSS increased the relative abundance of Parabacteroides distasonis in the colon of CUMS mice, and increased serum levels of various BAs including hyocholic acid (HCA) and 7-ketodeoxycholic acid (7-ketoDCA). Furthermore, gut bacteria transplantation from CSS-treated mice into untreated or cholestyramine-treated CUMS mice restored serum levels of HCA and 7-ketoDCA, alleviating depression-like symptoms. In the hippocampus, CSS-treated mice had decreased expression of genes associated with BA transport (Bsep and Fxr) and increased expression of brain-derived neurotrophic factor and its receptor, TrkB. Overall, CSS increases intestinal P. distasonis abundance, leading to elevated levels of secondary BAs in the circulation and altered expression of hippocampal genes implicated in BA transport and neurotrophic signaling. Our data strongly suggest that the gut microbiota-brain axis contributes to the potent antidepressant action of CSS by modulating BA metabolism. |
format | Online Article Text |
id | pubmed-9627339 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96273392022-11-03 Chaihu-shugan-san alleviates depression-like behavior in mice exposed to chronic unpredictable stress by altering the gut microbiota and levels of the bile acids hyocholic acid and 7-ketoDCA Ma, Chong Yuan, Dun Renaud, Stephen James Zhou, Ting Yang, Fan Liou, Yuligh Qiu, Xinjian Zhou, Lu Guo, Ying Front Pharmacol Pharmacology Chaihu-Shugan-San (CSS) is a traditional botanical drug formula often prescribed to treat depression in oriental countries, but its pharmacotherapeutic mechanism remains unknown. It was recently reported that CSS alters the composition of intestinal microflora and related metabolites such as bile acids (BAs). Since the intestinal microflora affects physiological functions of the brain through the gut-microbiota-brain axis, herein we investigated whether CSS altered BA levels, gut microflora, and depression-like symptoms in chronic unpredictable mild stress (CUMS) mice, a well-established mouse model of depression. Furthermore, we determined whether BA manipulation and fecal microbiota transplantation altered CSS antidepressant actions. We found that the BA chelator cholestyramine impaired the antidepressant effects of CSS, which was partially rescued by dietary cholic acid. CSS increased the relative abundance of Parabacteroides distasonis in the colon of CUMS mice, and increased serum levels of various BAs including hyocholic acid (HCA) and 7-ketodeoxycholic acid (7-ketoDCA). Furthermore, gut bacteria transplantation from CSS-treated mice into untreated or cholestyramine-treated CUMS mice restored serum levels of HCA and 7-ketoDCA, alleviating depression-like symptoms. In the hippocampus, CSS-treated mice had decreased expression of genes associated with BA transport (Bsep and Fxr) and increased expression of brain-derived neurotrophic factor and its receptor, TrkB. Overall, CSS increases intestinal P. distasonis abundance, leading to elevated levels of secondary BAs in the circulation and altered expression of hippocampal genes implicated in BA transport and neurotrophic signaling. Our data strongly suggest that the gut microbiota-brain axis contributes to the potent antidepressant action of CSS by modulating BA metabolism. Frontiers Media S.A. 2022-10-19 /pmc/articles/PMC9627339/ /pubmed/36339629 http://dx.doi.org/10.3389/fphar.2022.1040591 Text en Copyright © 2022 Ma, Yuan, Renaud, Zhou, Yang, Liou, Qiu, Zhou and Guo. 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 Ma, Chong Yuan, Dun Renaud, Stephen James Zhou, Ting Yang, Fan Liou, Yuligh Qiu, Xinjian Zhou, Lu Guo, Ying Chaihu-shugan-san alleviates depression-like behavior in mice exposed to chronic unpredictable stress by altering the gut microbiota and levels of the bile acids hyocholic acid and 7-ketoDCA |
title | Chaihu-shugan-san alleviates depression-like behavior in mice exposed to chronic unpredictable stress by altering the gut microbiota and levels of the bile acids hyocholic acid and 7-ketoDCA |
title_full | Chaihu-shugan-san alleviates depression-like behavior in mice exposed to chronic unpredictable stress by altering the gut microbiota and levels of the bile acids hyocholic acid and 7-ketoDCA |
title_fullStr | Chaihu-shugan-san alleviates depression-like behavior in mice exposed to chronic unpredictable stress by altering the gut microbiota and levels of the bile acids hyocholic acid and 7-ketoDCA |
title_full_unstemmed | Chaihu-shugan-san alleviates depression-like behavior in mice exposed to chronic unpredictable stress by altering the gut microbiota and levels of the bile acids hyocholic acid and 7-ketoDCA |
title_short | Chaihu-shugan-san alleviates depression-like behavior in mice exposed to chronic unpredictable stress by altering the gut microbiota and levels of the bile acids hyocholic acid and 7-ketoDCA |
title_sort | chaihu-shugan-san alleviates depression-like behavior in mice exposed to chronic unpredictable stress by altering the gut microbiota and levels of the bile acids hyocholic acid and 7-ketodca |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9627339/ https://www.ncbi.nlm.nih.gov/pubmed/36339629 http://dx.doi.org/10.3389/fphar.2022.1040591 |
work_keys_str_mv | AT machong chaihushugansanalleviatesdepressionlikebehaviorinmiceexposedtochronicunpredictablestressbyalteringthegutmicrobiotaandlevelsofthebileacidshyocholicacidand7ketodca AT yuandun chaihushugansanalleviatesdepressionlikebehaviorinmiceexposedtochronicunpredictablestressbyalteringthegutmicrobiotaandlevelsofthebileacidshyocholicacidand7ketodca AT renaudstephenjames chaihushugansanalleviatesdepressionlikebehaviorinmiceexposedtochronicunpredictablestressbyalteringthegutmicrobiotaandlevelsofthebileacidshyocholicacidand7ketodca AT zhouting chaihushugansanalleviatesdepressionlikebehaviorinmiceexposedtochronicunpredictablestressbyalteringthegutmicrobiotaandlevelsofthebileacidshyocholicacidand7ketodca AT yangfan chaihushugansanalleviatesdepressionlikebehaviorinmiceexposedtochronicunpredictablestressbyalteringthegutmicrobiotaandlevelsofthebileacidshyocholicacidand7ketodca AT liouyuligh chaihushugansanalleviatesdepressionlikebehaviorinmiceexposedtochronicunpredictablestressbyalteringthegutmicrobiotaandlevelsofthebileacidshyocholicacidand7ketodca AT qiuxinjian chaihushugansanalleviatesdepressionlikebehaviorinmiceexposedtochronicunpredictablestressbyalteringthegutmicrobiotaandlevelsofthebileacidshyocholicacidand7ketodca AT zhoulu chaihushugansanalleviatesdepressionlikebehaviorinmiceexposedtochronicunpredictablestressbyalteringthegutmicrobiotaandlevelsofthebileacidshyocholicacidand7ketodca AT guoying chaihushugansanalleviatesdepressionlikebehaviorinmiceexposedtochronicunpredictablestressbyalteringthegutmicrobiotaandlevelsofthebileacidshyocholicacidand7ketodca |