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
Obesity is a major risk factor for a variety of diseases such as diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Restricting energy intake, or caloric restriction (CR), can reduce body weight and improve metabolic parameters in overweight or obese patients. We previously found that Lingguizhugan decoction (LZD) in combination with CR can effectively lower plasma lipid levels in patients with metabolic syndrome. However, the mechanism underlying CR and LZD treatment is still unclear.
To investigate whether CR and LZD improve metabolic parameters by modulating gut microbiota.
We extracted the water-soluble components out of raw materials and dried as LZD extracts. Eight-week old male C57BL/6 mice were treated with a 3-d treatment regime that included 24 h-fasting followed by gavage of LZD extracts for 2 consecutive days, followed by a normal diet (ND) ad libitum for 16 wk. To test the effects of gut microbiota on diet-induced obesity, 8-wk old male C57BL/6 mice received fecal microbiota transplantation (FMT) from CR and LZD-treated mice every 3 d and were fed with high-fat diet (HFD) ad libitum for 16 wk. Control mice received either saline gavage or FMT from ND-fed mice receiving saline gavage as mentioned above. Body weight was monitored bi-weekly. Food consumption of each cage hosting five mice was recorded weekly. To monitor blood glucose, total cholesterol, and total triglycerides, blood samples were collected via submandibular bleeding after 6 h fasting. Oxygen consumption rate was monitored with metabolic cages. Feces were collected, and fecal DNA was extracted. Profiles of gut microbiota were mapped by metagenomic sequencing.
We found that CR and LZD treatment significantly reduced the body weight of mice fed with ND (28.71 ± 0.29 vs 28.05 ± 0.15, P < 0.05), but did not affect plasma total cholesterol or total triglyceride levels. We then transplanted the fecal microbiota collected from CR and LZD-treated mice under ND feeding to HFD-fed mice. Intriguingly, transplanting the mice with fecal microbiota from CR and LZD-treated mice potently reduced body weight (44.95 ± 1.02 vs 40.53 ± 0.97, P < 0.001). FMT also reduced HFD-induced hepatosteatosis, in addition to improved glycemic control. Mechanistic studies found that FMT increased OCR of the mice and suppressed the expression and protein abundance of lipogenic genes in the liver. Metagenomic analysis revealed that HFD drastically altered the profile of gut microbiota, and FMT modified the profile of the gut microbiota.
Our study suggests that CR and LZD improve metabolic parameters by modulating gut microbiota.
Core tip: This study shows that caloric restriction (CR) together with Lingguizhugan decoction (LZD) only slightly reduce body weight and blood glucose levels of normal diet (ND)-fed mice. Yet, transplanting the fecal microbiota of these mice into high-fat diet (HFD)-fed mice potently attenuated diet-induced obesity, hepatic steatosis, and hyperglycemia. Moreover, we found that fecal microbiota transplantation increases oxygen consumption rate of the mice and suppresses hepatic lipid biosynthesis. Using metagenomic sequencing, we further discovered that CR and LZD treatment alters the profile of ND-fed mice, and fecal microbiota transplantation alters HFD-induced changes in gut microbiota. Taken together, our study highlights that CR and LZD treatment exerts its metabolic improving effects via modulating gut microbiota.