Melatonin prevents obesity through modulation of gut microbiota in mice
TL;DR: It is suggested 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.
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.
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TL;DR: Melatonin’s high concentrations and multiple actions as an antioxidant provide potent antioxidant protection to these organelles which are exposed to abundant free radicals, particularly when they are under high oxidative stress conditions.
Abstract: Melatonin is an ancient antioxidant. After its initial development in bacteria, it has been retained throughout evolution such that it may be or may have been present in every species that have existed. Even though it has been maintained throughout evolution during the diversification of species, melatonin’s chemical structure has never changed; thus, the melatonin present in currently living humans is identical to that present in cyanobacteria that have existed on Earth for billions of years. Melatonin in the systemic circulation of mammals quickly disappears from the blood presumably due to its uptake by cells, particularly when they are under high oxidative stress conditions. The measurement of the subcellular distribution of melatonin has shown that the concentration of this indole in the mitochondria greatly exceeds that in the blood. Melatonin presumably enters mitochondria through oligopeptide transporters, PEPT1, and PEPT2. Thus, melatonin is specifically targeted to the mitochondria where it seems to function as an apex antioxidant. In addition to being taken up from the circulation, melatonin may be produced in the mitochondria as well. During evolution, mitochondria likely originated when melatonin-forming bacteria were engulfed as food by ancestral prokaryotes. Over time, engulfed bacteria evolved into mitochondria; this is known as the endosymbiotic theory of the origin of mitochondria. When they did so, the mitochondria retained the ability to synthesize melatonin. Thus, melatonin is not only taken up by mitochondria but these organelles, in addition to many other functions, also probably produce melatonin as well. Melatonin’s high concentrations and multiple actions as an antioxidant provide potent antioxidant protection to these organelles which are exposed to abundant free radicals.
343 citations
Cites background from "Melatonin prevents obesity through ..."
..., oncostatic [24, 25], anti-inflammatory [26–30], circadian rhythm modulation [31, 32], sleep promotion [33, 34], anti-venom [35, 36], body weight regulation [37, 38], anti-diabetic [39, 40], anti-fibrotic [41, 42], and others....
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TL;DR: Probiotics treatment can mitigate diet-induced obesity partly through modulating intestinal microbiota, especially in HCD-induced Obesity.
272 citations
TL;DR: It is suggested that melatonin improves lipid metabolism in high‐fat diet‐fed mice, and the potential mechanisms may be associated with reprogramming gut microbiota, especially, Bacteroides and Alistipes‐mediated acetic acid production.
Abstract: Melatonin has been shown to improve lipid metabolism and gut microbiota communities in animals and humans; however, it remains to know whether melatonin prevents obesity through gut microbiota. Here, we found that high-fat diet promoted the lipid accumulation and intestinal microbiota dysbiosis in mice, while oral melatonin supplementation alleviated the lipid accumulation and reversed gut microbiota dysbiosis, including the diversity of intestinal microbiota, relative abundances of Bacteroides and Alistipes, and functional profiling of microbial communities, such as energy metabolism, lipid metabolism, and carbohydrate metabolism. Interestingly, melatonin failed to alleviate the high-fat-induced lipid accumulation in antibiotic-treated mice; however, microbiota transplantation from melatonin-treated mice alleviated high-fat diet-induced lipid metabolic disorders. Notably, short-chain fatty acids were decreased in high-fat diet-fed mice, while melatonin treatment improved the production of acetic acid. Correlation analysis found a marked correlation between production of acetic acid and relative abundances of Bacteroides and Alistipes. Importantly, sodium acetate treatment also alleviated high-fat diet-induced lipid metabolic disorders. Taken together, our results suggest that melatonin improves lipid metabolism in high-fat diet-fed mice, and the potential mechanisms may be associated with reprogramming gut microbiota, especially, Bacteroides and Alistipes-mediated acetic acid production. Future studies are needed for patients with metabolic syndrome to fully understand melatonin's effects on body weight and lipid profiles and the potential mechanism of gut microbiota.
252 citations
TL;DR: This study demonstrates that RSV-induced microbiota plays a key role in controlling obesity development and brings new insights to a potential therapy based on host–microbe interactions.
Abstract: Resveratrol (RSV) is a natural polyphenol with putative anti-obesity effects; however, its mechanisms of action remain unclear due to its low bioavailability. Microbial functions in the physiology result from the microbiota–host coevolution has profoundly affected host metabolism. Here, we sought to determine how beneficial microbiome caused by RSV interventions affects antiobesity. C57BL/6J mice were fed either standard diet (SD) or RSV (300 mg/kg/day) diet for 16 weeks. The composition of the gut microbiota was assessed by analyzing 16S rRNA gene sequences. Then, transplant the RSV-microbiota to high-fat diet (HFD)-fed mice (HFD-RSVT) to explore the function of microbiota. Body weight and food intake were monitored. Markers of lipid metabolism, inflammation, gut microbiota compostion, and intestinal barrier were determined. Mice treated with RSV shows a remarkable alteration in microbiota composition compared with that of SD-fed mice and is characterized by an enrichment of Bacteroides, Lachnospiraceae_NK4A136_group, Blautia, Lachnoclostridium, Parabacteroides, and Ruminiclostridium_9, collectively referred to as RSV-microbiota. We further explored whether RSV-microbiota has anti-obesity functions. Transplantation of the RSV-microbiota to high-fat diet (HFD)-fed mice (HFD-RSVT) was sufficient to decrease their weight gain and increase their insulin sensitivity. Moreover, RSV-microbiota was able to modulate lipid metabolism, stimulate the development of beige adipocytes in WAT, reduce inflammation and improve intestinal barrier function. Our study demonstrates that RSV-induced microbiota plays a key role in controlling obesity development and brings new insights to a potential therapy based on host–microbe interactions.
167 citations
References
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TL;DR: An overview of the analysis pipeline and links to raw data and processed output from the runs with and without denoising are provided.
Abstract: Supplementary Figure 1 Overview of the analysis pipeline. Supplementary Table 1 Details of conventionally raised and conventionalized mouse samples. Supplementary Discussion Expanded discussion of QIIME analyses presented in the main text; Sequencing of 16S rRNA gene amplicons; QIIME analysis notes; Expanded Figure 1 legend; Links to raw data and processed output from the runs with and without denoising.
28,911 citations
TL;DR: UCLUST is a new clustering method that exploits USEARCH to assign sequences to clusters and offers several advantages over the widely used program CD-HIT, including higher speed, lower memory use, improved sensitivity, clustering at lower identities and classification of much larger datasets.
Abstract: Motivation: Biological sequence data is accumulating rapidly, motivating the development of improved high-throughput methods for sequence classification.
Results: UBLAST and USEARCH are new algorithms enabling sensitive local and global search of large sequence databases at exceptionally high speeds. They are often orders of magnitude faster than BLAST in practical applications, though sensitivity to distant protein relationships is lower. UCLUST is a new clustering method that exploits USEARCH to assign sequences to clusters. UCLUST offers several advantages over the widely used program CD-HIT, including higher speed, lower memory use, improved sensitivity, clustering at lower identities and classification of much larger datasets.
Availability: Binaries are available at no charge for non-commercial use at http://www.drive5.com/usearch
Contact: [email protected]
Supplementary information:Supplementary data are available at Bioinformatics online.
17,301 citations
TL;DR: It is demonstrated through metagenomic and biochemical analyses that changes in the relative abundance of the Bacteroidetes and Firmicutes affect the metabolic potential of the mouse gut microbiota and indicates that the obese microbiome has an increased capacity to harvest energy from the diet.
Abstract: The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.
10,126 citations
TL;DR: FLASH is a fast computational tool to extend the length of short reads by overlapping paired-end reads from fragment libraries that are sufficiently short and when FLASH was used to extend reads prior to assembly, the resulting assemblies had substantially greater N50 lengths for both contigs and scaffolds.
Abstract: Motivation: Next-generation sequencing technologies generate very large numbers of short reads. Even with very deep genome coverage, short read lengths cause problems in de novo assemblies. The use of paired-end libraries with a fragment size shorter than twice the read length provides an opportunity to generate much longer reads by overlapping and merging read pairs before assembling a genome.
Results: We present FLASH, a fast computational tool to extend the length of short reads by overlapping paired-end reads from fragment libraries that are sufficiently short. We tested the correctness of the tool on one million simulated read pairs, and we then applied it as a pre-processor for genome assemblies of Illumina reads from the bacterium Staphylococcus aureus and human chromosome 14. FLASH correctly extended and merged reads >99% of the time on simulated reads with an error rate of <1%. With adequately set parameters, FLASH correctly merged reads over 90% of the time even when the reads contained up to 5% errors. When FLASH was used to extend reads prior to assembly, the resulting assemblies had substantially greater N50 lengths for both contigs and scaffolds.
Availability and Implementation: The FLASH system is implemented in C and is freely available as open-source code at http://www.cbcb.umd.edu/software/flash.
Contact: moc.liamg@cogam.t
9,827 citations
TL;DR: In this paper, the authors estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010.
9,324 citations