Ameliorative effect of Aconite aqueous extract on diarrhea is associated with modulation of the gut microbiota and bile acid metabolism

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Abstract

Introduction: Aconite is a form of traditional Chinese medicine (TCM) that has been widely used to treat diarrhea for thousands of years. However, it is not clear whether the anti-diarrhea role of aconite aqueous extract (AA) is associated with regulation of the gut microbiota or with bile acid (BA) metabolism. This study aimed to confirm whether AA exerts its anti-diarrhea effects by regulating the gut microbiota and BA metabolism.

Methods: The therapeutic effect of AA in a mouse model of diarrhea was measured based on analysis of body weight, fecal water content, diarrhea scores, intestinal propulsion rate, colonic pathology, and colonic immunohistochemistry. In addition, 16S rRNA high-throughput sequencing was conducted to analyze the effect of AA on the gut microbiota, and targeted metabolomics was employed to analyze the effect of AA on metabolism of BAs.

Results: The results showed that treatment with AA reduced fecal water content and diarrhea scores, inhibited intestinal propulsion rate and pathological changes in the colon, and increased AQP3 and AQP4 content in the colon. In addition, AA was found to be capable of regulating the gut microbiota. Effects included increasing its richness (according to the ACE and Chao1 indices); altering the gut microbiota community structure (PCA, PCoA, and NMDS); increasing the relative abundance of norank_f_Muribaculaceae, Ruminococcus, Lachnospiraceae_NK4A136_group, Prevotellaceae_UCG-001, and norank_f_norank_o_Clostridia_UCG-014; and decreasing the relative abundance of Escherichia-Shigella, unclassified_f_Ruminococcaceae, Ruminococcus_torques_group, and Parasutterella. More importantly, AA significantly increased fecal TCA (a primary BA) and DCA, LCA, GDCA, dehydro-LCA, and 12-keto-LCA (secondary BAs), thus restoring BA homeostasis. Moreover, AA increased the ratios of DCA/CA, DCA/TCA, and LCA/CDCA and decreased the ratios of TLCA/LCA, GLCA/LCA, and TUDCA/UDCA.

Conclusion: The anti-diarrhea effect of AA was associated with restoration of the gut microbiota and BA metabolism-related homeostasis. The results of this study provide insights into the application of AA and the treatment of diarrhea.

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Most cited references 63

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Bile acid–microbiota crosstalk in gastrointestinal inflammation and carcinogenesis

Wei Jia, Weiping Jia, Guoxiang Xie (2017)

Emerging evidence points to a strong association between the gut microbiota and the risk, development and progression of gastrointestinal cancers such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Bile acids, produced in the liver, are metabolized by enzymes derived from intestinal bacteria and are critically important for maintaining a healthy gut microbiota, balanced lipid and carbohydrate metabolism, insulin sensitivity and innate immunity. Given the complexity of bile acid signalling and the direct biochemical interactions between the gut microbiota and the host, a systems biology perspective is required to understand the liver-bile acid-microbiota axis and its role in gastrointestinal carcinogenesis to reverse the microbiota-mediated alterations in bile acid metabolism that occur in disease states. An examination of recent research progress in this area is urgently needed. In this Review, we discuss the mechanistic links between bile acids and gastrointestinal carcinogenesis in CRC and HCC, which involve two major bile acid-sensing receptors, farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5). We also highlight the strategies and cutting-edge technologies to target gut-microbiota-dependent alterations in bile acid metabolism in the context of cancer therapy.

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Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation

Sidhartha Sinha, Yeneneh Haileselassie, Linh P Nguyen … (2020)

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Defining the role of Parasutterella, a previously uncharacterized member of the core gut microbiota

Tingting Ju, Ji Yoon Kong, Paul Stothard … (2019)

The genus of Parasutterella has been defined as a core component of the human and mouse gut microbiota, and has been correlated with various health outcomes. However, like most core microbes in the gastrointestinal tract (GIT), very little is known about the biology of Parasutterella and its role in intestinal ecology. In this study, Parasutterella was isolated from the mouse GIT and characterized in vitro and in vivo. Mouse, rat, and human Parasutterella isolates were all asaccharolytic and producers of succinate. The murine isolate stably colonized the mouse GIT without shifting bacterial composition. Notable changes in microbial-derived metabolites were aromatic amino acid, bilirubin, purine, and bile acid derivatives. The impacted bile acid profile was consistent with altered expression of ileal bile acid transporter genes and hepatic bile acid synthesis genes, supporting the potential role of Parasutterella in bile acid maintenance and cholesterol metabolism. The successful colonization of Parasutterella with a single environmental exposure to conventional adult mice demonstrates that it fills the ecological niche in the GIT and contributes to metabolic functionalities. This experiment provides the first indication of the role of Parasutterella in the GIT, beyond correlation, and provides insight into how it may contribute to host health.

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Author and article information

Contributors

Wuwen Feng: URI : https://loop.frontiersin.org/people/1205669/overview

Cheng Peng: URI : https://loop.frontiersin.org/people/499544/overview

Journal

Journal ID (nlm-ta): Front Pharmacol

Journal ID (iso-abbrev): Front Pharmacol

Journal ID (publisher-id): Front. Pharmacol.

Title: Frontiers in Pharmacology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1663-9812

Publication date (Electronic): 17 May 2023

Publication date Collection: 2023

Volume: 14

Electronic Location Identifier: 1189971

Affiliations

[1] ¹ State Key Laboratory of Southwestern Chinese Medicine Resources , School of Pharmacy , Chengdu University of Traditional Chinese Medicine , Chengdu, China

[2] ² Key Laboratory of the Ministry of Education for Standardization of Chinese Medicine , Chengdu University of Traditional Chinese Medicine , Chengdu, China

[3] ³ School of Basic Medical Sciences , Chengdu University of Traditional Chinese Medicine , Chengdu, China

[4] ⁴ Hospital of Chengdu University of Traditional Chinese Medicine , Chengdu, China

Author notes

Edited by: Jiyan Su, South Medical University Affiliated Maternal and Child Health Hospital of Foshan, China

Reviewed by: Dake Cai, Guangdong Second Hospital of Traditional Chinese Medicine, China

Jia-bo Wang, Capital Medical University, China

*Correspondence: Wuwen Feng, jiaoxiake-1@ 123456foxmail.com ; Cheng Peng, pengchengcxy@ 123456126.com

Article

Publisher ID: 1189971

DOI: 10.3389/fphar.2023.1189971

PMC ID: 10229775

PubMed ID: 37266146

SO-VID: d753a3d5-3197-4810-aed1-e3e855fb2a02

License:

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.

History

Date received : 20 March 2023

Date accepted : 25 April 2023

Funding

Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;

Award ID: No. 82104409 No. 81891012 No. 81891010 No. U19A2010

This work was supported by the National Natural Science Foundation of China (Nos. 82104409, 81891012, 81891010, and U19A2010), the Science and Technology Ministry of China (2108ZX09721001-008), and the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202209).

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section-at-acceptance Gastrointestinal and Hepatic Pharmacology

ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine

Keywords: aconite aqueous extract,rhubarb,diarrhea,gut microbiota,bile acids

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ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine

Keywords: aconite aqueous extract, rhubarb, diarrhea, gut microbiota, bile acids

Ameliorative effect of Aconite aqueous extract on diarrhea is associated with modulation of the gut microbiota and bile acid metabolism

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Most cited references 63

Bile acid–microbiota crosstalk in gastrointestinal inflammation and carcinogenesis

Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation

Defining the role of Parasutterella, a previously uncharacterized member of the core gut microbiota

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