Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2019; 25(27): 3590-3606
Published online Jul 21, 2019. doi: 10.3748/wjg.v25.i27.3590
Lingguizhugan decoction attenuates diet-induced obesity and hepatosteatosis via gut microbiota
Meng-Ting Liu, Ying-Juan Huang, Ting-Ying Zhang, Lun-Bo Tan, Xi-Feng Lu, Jian Qin
Meng-Ting Liu, Ying-Juan Huang, Ting-Ying Zhang, Jian Qin, Department of Traditional Chinese Medicine, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Ting-Ying Zhang, Jian Qin, Department of Traditional Chinese Medicine, the Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, Guangdong Province, China
Lun-Bo Tan, Xi-Feng Lu, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, Shenzhen 518060, Guangdong Province, China
Author contributions: Qin J, Lu XF, and Liu MT designed the research; Liu MT, Huang YJ, and Zhang TY performed the research and analyzed the data; Liu MT, Qin J, and Tan LB wrote the manuscript; Lu XF extensively revised the manuscript for clarity and grammar.
Supported by the National Natural Science Foundation of China, No. 81874498.
Institutional review board statement: The study was reviewed and approved by the Seventh Affiliated Hospital of Sun Yat- Sen University Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Seventh Affiliated Hospital of Sun Yat-Sen University (2018-057).
Conflict-of-interest statement: The authors declare that there is no conflict of interest to be disclosed.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guideline.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Jian Qin, MD, PhD, Doctor, Professor, Department of Traditional Chinese Medicine, the Seventh Affiliated Hospital of Sun Yat-Sen University, No. 628, Zhenyuan Road, Guangming New District, Shenzhen 518107, Guangdong Province, China. jian.qin.sunyatsen@outlook.com
Telephone: +86-755-23242725 Fax: +86-755-23242725
Received: March 25, 2019
Peer-review started: March 26, 2019
First decision: May 16, 2019
Revised: May 30, 2019
Accepted: June 8, 2019
Article in press: June 8, 2019
Published online: July 21, 2019
Processing time: 116 Days and 9.1 Hours
ARTICLE HIGHLIGHTS
Research background

Lingguizhugan decoction (LZD) in combination with food restriction is widely used in clinical practice to treat patients with metabolic disorders, such as obesity, diabetes, high plasma lipid levels, and non-alcoholic fatty liver disease. Despite its wide application and effectiveness, little is known about its mechanism.

Research motivation

Although it is well accepted to use LZD in clinic to treat patients with metabolic disorders, lacking the knowledge on its mechanism has limited its use. Clarifying the pharmacological mechanism will provide scientific evidence for its clinic usage. Recent studies have revealed that traditional Chinese herbal medicines exert their effects by modulating gut microbiota, which has been previously unrecognized.

Research objectives

To investigate whether LZD combined with food restriction improves metabolic parameters via modulating gut microbiota.

Research methods

To answer this question, we administered LZD gavage in addition to food restriction to mice fed a normal diet, and monitored body weight, blood glucose, and plasma lipid levels. At the same time, we collected the feces of these mice and homogenized with saline. We gave these fecal homogenates, which contain microbes, to mice fed a high fat diet. As high fat diet increases body weight, it causes increases in plasma lipid levels and blood glucose levels and induces abnormal lipid accumulation in the liver. Thus, we studied the effects of giving fecal homogenates from LZD treated and food-restricted mice on diet-induced metabolic abnormalities.

Research results

We found that LZD together with food restriction slightly reduced body weight and blood glucose levels but did not affect plasma lipid levels. However, giving the fecal homogenates collected from LZD and food-restricted mice greatly reduced body weight, plasma lipid levels, hepatic lipid contents, and blood glucose levels of mice on a high-fat-diet. We also found that giving the mice fecal homogenates significantly promoted fat oxidation and inhibited fat synthesis. Using DNA sequencing techniques, we found that LZD together with food restriction significantly changed the composition of bacteria in the gut.

Research conclusions

We found that a widely used traditional Chinese medicine can change the bacteria composition of the gut. Transferring these gut bacteria into high-fat-diet fed mice can reduce diet-induced increase in blood glucose, plasma lipid levels, hepatic lipid contents and body weight gain. Thus, gut microbes are the most likely primary target of LZD and food restriction treatment.

Research perspectives

Our study highlights the possibility of using bacteria to treat metabolic disorders such as obesity in the future. Using metagenomics, metatranscriptomic sequencing, and fecal metabolomics, it is possible to identify the most important bacteria and metabolites underlying the treatment of LZD and food restriction. This will make it possible to culture the identified bacteria in vivo and treat them with LZD extracts. Then giving the patients with such cultured and treated bacteria would provide similar effects as LZD treatment, thus reducing any potential toxic effects of the herbal medicine.