Effect of fecal microbiota transplantation on “intestinal flora-SCFAs-GPR43 - gastrointestinal peptide” pathway in rats with high-fat diet

Objective To explore the effect of high-fat diet and fecal microbiota transplantation (FMT) on “intestinal flora-SCFAs-GPR43-gastrointestinal peptide” pathway, and provide evidence and clues for the prevention and treatment of obesity caused by eutrophic diet. Methods 160 male SD rats were used in this study, 50 of them were randomly selected to be fed a standard rat diet, while the remaining 110 rats were fed a high-fat diet (D12492). After excluding the rats that did not meet the obesity criteria, the remaining rats were subjected to treatment with normal microbiota enema and obesity-associated microbiota enema. The rats were divided into normal control group 1 (NC1), normal control group 2 (NC2), obesity model group (M), obesity fecal microbiota transplantation group (FMT1), and normal fecal microbiota transplantation group (FMT2). The study observed the general situation, the index of liver, spleen and thymus in rats. Morphological changes of colon and liver tissues were examined under an optical microscope, and the alterations in gut microbiota were detected by 16s rDNA. Gas chromatography-mass spectrometry (GC-MS) was ued to measure the levels of short-chain fatty acids (SCFAs), including acetic acid, propionic acid, and butyric acid. Immunohistochemistry (IHC) was used to evaluate the expression of GPR43 in liver tissue. Additionally, gastrointestinal peptides in rat serum were quantified using the ELISA method, while cholesterol and triglyceride levels in serum were measured using an automatic biochemical analyzer. Results The high-fat diet successfully induced obesity rat models. This led to significant changes in gut environment and the survival environment of microbiota, such as Lactobacillus, reflecting the intestinal microecological disorders in rats with high-fat diet induced obesity, Different dietary interventions can lead to varing developments in gut microbiota. After antibiotic intervention, gut microbiota in rats were significantly suppressed, with reduced species diveristy and abundance, establishing an antibiotic-induced rat model. High-fat diet interventions resulted in significant changes in the relative abundances of specific gut bacterial species. Further analysis of microbial metabolites displayed that a high-calorie diet reduced the content of short-chain fatty acids (SCFAs) in feces, and subsequently reduced the expression of GPR43, resulting in improved abnormal expression of downstream gastrointestinal peptide. Conclusions High-fat diet affects the intestinal flora-SCFAs-GPR43-gastrointestinal peptide pathway, leading to related pathological reactions, such as intestinal flora imbalance and short-chain fatty acid metabolism disorders, which in return activates GPR43, and releases PYY, GLP-1, GAS, MTL, causing lipid and energy metabolism disorders in the body. Fecal microbiota transplantation (FMT) can colonize the intestinal tract of obese rats, improving the abundance, diversity and the structure of the flora, activating GPR43 and the downstream mechanisms. This regulation of peptide hormone secretion by endocrine cells can improve metabolic disorders caused by a high-fat diet and may play a significant role in preventing and treating obesity.