Published online Jul 21, 2019. doi: 10.3748/wjg.v25.i27.3590
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
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.
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.
To investigate whether LZD combined with food restriction improves metabolic parameters via modulating gut microbiota.
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.
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.
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.
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.