Effects of Clostridium tyrobutyricum on Lipid Metabolism, Intestinal Barrier Function, and Gut Microbiota in Obese Mice Induced by High-Fat Diet

Obesity and its complications constitute a main threat to global human health. The purpose of this investigation was to explore the influences of Clostridium tyrobutyricum (Ct) on lipid metabolism, intestinal barrier function, and intestinal microbiome in obese mice induced by a high-fat diet (HFD). After establishing the obesity model, 10(7) CFU/mL and 10(8) CFU/mL C. tyrobutyricum were used to intervene in HFD-fed mice by gavage for six weeks, and indexes related to obesity were measured. In the liver of HFD-fed mice, the results revealed that C. tyrobutyricum reduced liver weight and the levels of triglyceride (TG), total cholesterol (TC), and nonesterified fatty acid (NEFA), along with decreasing red lipid droplets and fat vacuoles. After C. tyrobutyricum intervention, the mRNA expression of peroxisome proliferator-activated receptor-gamma (PPAR gamma) was downregulated, and AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-alpha (PPAR alpha), adipose triglyceride lipase (ATGL), and hormone-sensitive lipase (HSL) were upregulated in the liver. Additionally, C. tyrobutyricum alleviated intestinal morphology injury caused by HFD, decreased the expression of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and IL-1 beta in the colon, and upregulated tight junction protein expression. In addition, 16S rRNA sequencing revealed that C. tyrobutyricum increases the diversity of intestinal microbiota. Overall, C. tyrobutyricum improved HFD-induced lipid metabolism disorders, preserved the intestinal barrier's integrity, and modulated the structure of the intestinal microbiome. These findings provide a novel insight into the role of C. tyrobutyricum as a probiotic in regulating lipid metabolism.