LAUSR

High‐fat diet‐induced obesity is characterized by low‐grade inflammation, which has been linked to gut microbiota dysbiosis. We hypothesized that quercetin supplementation would alter gut microbiota and reduce inflammation in obese mice. Male C57BL/6J mice, 4 weeks of age, were divided into 3 groups, including a low‐fat diet group, a high‐fat diet (HFD) group, and a high‐fat diet plus quercetin (HFD+Q) group. The mice in HFD+Q group were given 50 mg per kg BW quercetin by gavage for 20 weeks. The body weight, fat accumulation, gut barrier function, glucose tolerance, and adipose tissue inflammation were determined in mice. 16 s rRNA amplicon sequence and non‐targeted metabolomics analysis were used to explore the alteration of gut microbiota and metabolites. We found that quercetin significantly alleviated HFD‐induced obesity, improved glucose tolerance, recovered gut barrier function, and reduced adipose tissue inflammation. Moreover, quercetin ameliorated HFD‐induced gut microbiota disorder by regulating the abundance of gut microbiota, such as Adlercreutzia, Allobaculum, Coprococcus_1, Lactococcus, and Akkermansia. Quercetin influenced the production of metabolites that were linked to alterations in obesity‐related inflammation and oxidative stress, such as Glycerophospho‐N‐palmitoyl ethanolamine, sanguisorbic acid dilactone, O‐Phospho‐L‐serine, and P‐benzoquinone. Our results demonstrate that the anti‐obesity effects of quercetin may be mediated through regulation in gut microbiota and metabolites.