Ferulic acid improves intestinal barrier function through altering gut microbiota composition in high-fat diet-induced mice

A high-fat diet (HFD) induces gut microbiota (GM) disorders, leading to intestinal barrier dysfunction and inflammation. Ferulic acid (FA) has shown anti-obesity effects, e.g., reducing body weight and food intake. However, the mechanism linking the anti-obesity effects of FA and GM modulation remains obscure. The present study aimed to clarify the mechanism underlying the anti-obesity effects of FA and modulation of the GM.C57BL/6 J mice were fed by a low-fat diet (LFD) and HFD with or without FA at a dose of 100 mg/kg of body weight by oral gavage for 12 weeks. Using high-throughput sequencing, gas chromatography, real-time fluorescence quantitative PCR and immunohistochemical staining, the attenuation of obesity by FA were assessed via intestinal barrier integrity, inflammation, and the GM.FA reduced weight gain, improved HFD-induced GM imbalance, significantly enhanced intestinal short-chain fatty acid (SCFA)-producing bacteria (e.g., Olsenella, Eisenbergiella, Dubosiella, Clostridiales_unclassified, and Faecalibaculum) along with SCFA accumulation and its receptors' expression, decreased endotoxin-producing bacteria or obesity-related bacterial genera, and serum endotoxin (lipopolysaccharides), and inhibited the colonic TLR4/NF-κB pathway. Thus, FA can mitigate colonic barrier dysfunction and intestinal inflammation, induce the production of SCFAs and inhibit endotoxins by modulating the GM.These results indicate that enhancement of intestinal barrier by altering the GM may be an anti-obesity target of FA and that FA can be used as a functional compound with great developmental values.