Melatonin prevents obesity through modulation of gut microbiota in mice

Abstract

Excess weight and obesity are severe public health threats worldwide. Recent evidence demonstrates that gut microbiota dysbiosis contributes to obesity and its comorbidities. The body weight-reducing and energy balancing effects of melatonin have been reported in several studies, but to date, no investigations toward examining whether the beneficial effects of melatonin are associated with gut microbiota have been carried out. In this study, we show that melatonin reduces body weight, liver steatosis, and low-grade inflammation as well as improving insulin resistance in high fat diet (HFD)-fed mice. High-throughput pyrosequencing of the 16S rRNA demonstrated that melatonin treatment significantly changed the composition of the gut microbiota in mice fed an HFD. The richness and diversity of gut microbiota were notably decreased by melatonin. HFD feeding altered 69 operational taxonomic units (OTUs) compare with a normal chow diet (NCD) group, and melatonin supplementation reversed 14 OTUs to the same configuration than those present in the NCD group, thereby impacting various functions, in particular through its ability to decrease the Firmicutes-to-Bacteroidetes ratio and increase the abundance of mucin-degrading bacteria Akkermansia, which is associated with healthy mucosa. Taken together, our results suggest that melatonin may be used as a probiotic agent to reverse HFD-induced gut microbiota dysbiosis and help us to gain a better understanding of the mechanisms governing the various melatonin beneficial effects.

Role of melatonin in sleep deprivation‐induced intestinal barrier dysfunction in mice

“…Improvements in intestinal barrier dysfunction were substantial at the high dose (40.0 mg/kg) of MT supplementation (SD + 2MT group). Previous studies have reported that MT treatment significantly changes the richness, diversity and composition of the gut microbiota in both murine models of obesity and weanling stress . These results indicate that MT suppression plays a crucial role in SD‐induced intestinal homoeostasis disorder.…”

“…Studies have reported that the MT concentration is approximately 2000‐11 000 pg/mL in the bile to prevent small intestinal epithelial injury . Previous compelling investigations have demonstrated that MT influences the swarming and motility of Enterobacter aerogenes, the richness and diversity of the mouse intestinal microbiota, the ratio of Firmicutes to Bacteroidetes (F:B) and the abundance of Akkermansia . However, few clinical or experimental studies have evaluated the effect of MT on gut microbiota dysbiosis and the loss of intestinal mucosal integrity induced by SD.…”

Reduced delivery of epididymal adipocyte‐derived exosomal resistin is essential for melatonin ameliorating hepatic steatosis in mice

“…Melatonin plays a vital role in the amelioration of metabolic disorders in various organs/tissues, including adipose tissue and liver . Although previous studies have already discussed that melatonin enables obesity‐induced dysmetabolism of adipose tissue and hepatic steatosis to be reversed, little focused on the regulatory efforts of melatonin on their crosstalk under HFD‐induced obese condition.…”

Melatonin potentiates the effects of metformin on glucose metabolism and food intake in high‐fat‐fed rats

“…Such anorectic effect, however, was found only in nondiabetic Wistar, but not in diabetic rats. In support to this view, a previous work has demonstrated that melatonin prevents diet-induced obesity in mice via counteracted changes in the composition of the microbiome (ie, dysbiosis), decrease in low-grade inflammation and oxidative stress, dyslipidaemia, as well as stimulation of browning in inguinal subcutaneous adipose tissue and improvement of insulin resistance 40. Among peripheral tissues, gut is a candidate to be affected by melatonin treatment.…”