Intervention effects of Er Miao san on metabolic syndrome in Bama miniature pigs.

Background: Metabolic syndrome (MS) refers to a cluster of metabolic disorders characterized by systemic chronic inflammation. Er Miao San (EMS) is a classic traditional Chinese medicine compound containing Phellodendron amurense and Atractylodis rhizome at a ratio of 1:1, proven to be effective against inflammatory diseases in clinical practice. Nevertheless, the precise functions of EMS in treating MS and its underlying mechanism have yet to be elucidated.

Purpose: This study focuses on the intervention effects of EMS on high humidity exposure and high sugar-fat diet (HHSF)-induced MS in pigs.

Study Design: Blood biochemical indices and metabolome analysis were employed to confirm the successful establishment of the MS model, and the preliminary evaluation of the intervention effect of EMS was conducted. Subsequently, a parallel microbiota analysis of the tongue and cecum was combined with metabolomic analysis, histopathologic examination, and other molecular biological detection to further assess the administration mechanism of EMS.

Results: The results demonstrated that EMS significantly reduced the excessive weight gain rate, fat accumulation, hyperlipidemia, hyperglycemia, and systemic inflammation while improving serum metabolic disorder in MS pigs. Moreover, microbiota analysis indicates that EMS restored the diversity and composition of oral-gut microbiota by increasing the proportions of Lactobacillus (gut), Roseburia (gut), Faecalibacterium (gut), CF231 (gut), Streptococcus (gut), Prevotella (gut), while decreasing those of Chryseobacterium (oral), Corynebacterium (oral), Clostridium (oral), Oscillospira (gut), and Turicibacter (oral, gut). Subsequently, EMS up-regulated the concentrations of acetic acid, butyric acid, propionic acid, while down-regulated isobutyric acid and isovaleric acid. This resulted in a suppression of HDAC3 expression and an increase of SCL16A1 expression in the colon. Notably, the changes in acetic acid and butyric acid showed a strong correlation with gut microbiota. Additionally, EMS reduced the serum level of lipopolysaccharide (LPS) and enhanced epithelial barrier integrity by inhibiting the LPS-TLR4/MyD88/NF-κB pathways.

Conclusions: EMS was found to ameliorate MS by alleviating the dysbiosis of the oral-gut microbiota and serum metabolome, thereby improving gut barrier and reducing systemic inflammation. These findings suggest that EMS holds promise as a therapeutic agent for MS.