Hydroxytyrosol Improves Obesity and Insulin Resistance by Modulating Gut Microbiota in High-Fat Diet-Induced Obese Mice.
Liu Z, Wang N, Ma Y, Wen D
Front Microbiol. 2019. doi: 10.3389/fmicb.2019.00390
COMMENT: Hydroxytyrosol (HT) is the main component of olive oil and it has been shown to have beneficial effects on obesity, inflammation, hyperglycemia, insulin resistance and oxidative stress, among others. However, there is a lack of research on the mechanism by which HT improves obesity and its effect on gut microbiota. In this study the changes of the gut microbiota after high-fat diet (HFD), hydroxytyrosol feeding (HT), and fecal microbiota transplantation experiments from mice supplemented with HT (HTF), were analyzed by 16S rRNA amplicon sequencing (V3-V4 region).
In the present study, the authors hypothesized that Hydroxytyrosol (HT) may prevent obesity and insulin resistance (IR) by altering the composition of the intestinal microbes and alleviating inflammatory status. The effect of HT supplementation on high-fat diet (HFD)-induced obese mice was analyzed, along with the mechanism of action of the gut microorganisms through bacterial fecal transplantation experiments.
HT gavage at a concentration of 50 mg/kg/day for 8 weeks was able to maintain the integrity of intestinal barrier, alter the composition of gut microbiota, reduce the release of endotoxin into the blood, and reduce inflammation, ultimately preventing HFD-induced obesity and IR.
It has found that HFD mice had a significantly increased ratio of Firmicutes to Bacteroides (F/B), which was not altered by Hydroxytyrosol (HT) or fecal microbiota transplantation from mice supplemented with HT. This indicates that HT may be beneficial for metabolism but does not regulate F/B.
We found that HT supplementation significantly changed the composition of the gut microbiota.
HT enhanced a variety of bacterial species that are negatively associated with obesity and reduced species that are positively associated with obesity. In summary, HT may prevent HFD-induced obesity by regulating a variety of different gut microbiota.
Fecal microbiota transplantation from mice supplemented with HT (HTF) also resulted in beneficial effects similar to those seen in HT-feeded mice, including an increase in the integrity of the intestinal barrier, prevention of inflammation, and alleviation of obesity and IR induced by a HFD. Furthermore, HFT altered the intestinal microbiota in a manner consistent with HT supplementation.
HT and HTF restrained the activation of the TLR-4 and NF-κB pathways, reduced the expression of pro-inflammatory factors and IRS-1 phosphorylation at serine 307, and enhanced the phosphorylation of AKT. Thus, HT may alleviate IR through the TLR-4 and NF-κB signaling pathways.
Overall, our results suggest that HT reduces weight gain, chronic inflammation, and IR in HFD-induced obese mice, partially through regulation of specific gut microbiota.