Oral Administration of Crocus sativus Tepals Extract Restores High‐Fat Diet‐Induced Gut Dysbiosis and Modulates Intestinal Inflammation and Hepatic Lipid Metabolism

Metabolic diseases have increased worldwide in recent decades, mainly due to a sedentary lifestyle and an unhealthy diet, with diet identified as an important regulator of gut microbiota composition. The use of natural products, such as Crocus sativus tepals extract (CTE) could be a promising approach to alleviate metabolic disorders. The aim was to investigate the potential ameliorative mechanisms of CTE in metabolic disorders induced by a high-fat diet in an animal model, focusing on the composition of the gut microbiota and its relationship with the gut-liver axis. We analyzed liver-related biochemical and morphological parameters in mice fed a 60% fat diet for 14 weeks and orally treated with CTE during the last 5 weeks of the diet. In addition, jejunal and liver histology, intestinal barrier integrity, inflammation and oxidative stress, liver inflammation and lipid metabolism were investigated. The results showed that oral administration of CTE restored the composition of the gut microbiota and specifically promoted short-chain fatty acids-producing and anti-inflammatory bacterial genera. It also improved intestinal barrier integrity and reduced inflammation in the jejunum and liver, along with a suppression of Fas and CerS6 expression in the liver and a reduction in circulating free fatty acids and β-hydroxybutyrate levels. Our results indicate a possible link between the gut microbiota and the metabolic benefits of treatment with CTE, suggesting its therapeutic potential for the prevention or treatment of metabolic disorders.