High-fat diet (HFD)-induced obesity is a risk factor for many metabolic disorders including cardiovascular diseases, diabetes, and fatty liver disease. Although there are accumulating evidences supporting the assumption that regulating gut microbiota as well as its metabolic status is able to mitigate obesity, the inner relationship between the obesity-related gut microbiota and the relevant metabolites are not well defined. In current study, we applied a traditional herbal formula Kang Shuai Lao Pian (KSLP) to HFD-fed mice and evaluated its effect against obesity. Emphases were addressed on identifying profiles of gut microbiota and fecal metabolites with the aid of 16S rRNA gene sequencing and non-target fecal metabolomics techniques. We showed that KSLP could improve HFD-induced obesity, glucose tolerance disorder, as well as gut dysbiosis. In the gut, KSLP corrected the increased abundance of Firmicutes and Proteobacteria, increased ratio of Firmicutes/Bacteroidetes, and decreased abundance of Bacteroidetes caused by HFD. KSLP also reversed HFD-induced significant changes in the abundance of certain genus including Intestinimonas, Oscillibacter, Christensenellaceae_R-7_group, Ruminococcaceae_UCG-010, and Aliihoeflea. Pearson correlation analysis indicated that except for Ruminococcaceae_UCG-010, other four genera had positive correlations with obesity. In addition, 22 key fecal metabolites responding to KSLP treatment were identified. Pearson correlation analysis showed that those metabolites are intimately related to KSLP effective genera of Intestinimonas, Oscillibacter, and Christensenellaceae_R-7_group. Our results indicate that KSLP is a promising traditional Chinese medicine (TCM) applicable for individuals with HFD habit. Intestinimonas, Oscillibacter, and Christensenellaceae_R-7_group might be responsible for the regulatory effect of KSLP. Linking of obesity phenotypes with gut microbiota as well as fecal metabolites is therefore a powerful research strategy to reveal the mechanism of obesity and the targets of intervention.

#	Concept	H-Index	Publications	Citations
1	Health Sciences	1	1	45
2	Medicine	1	1	32
3	Public Health	1	1	45
4	Social Sciences	1	1	32
5	Allergy	1	1	45

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