Impacts of Fecal Microbiota Transplantation on the Gut Microbiota-Short-Chain Fatty Acids-GPR43-Interleukin-18 Pathway in Rats Subjected to a High-Calorie Diet

Abstract

Background: A high-calorie diet (HCD) is a significant pathogenic factor contributing to obesity and can induce dysbiosis in the intestinal flora. Fecal microbiota transplantation (FMT) has been recognized for potentially restoring intestinal microecology. However, precise mechanisms underlying its therapeutic effects remain largely elusive. This study aimed to investigate the impact of FMT on the gut microbiota-short-chain fatty acids (SCFAs)-G protein-coupled receptor 43 (GPR43)-interleukin-18 (IL-18) pathway in HCD-induced rats. The findings provide insights and evidence for preventing and treating pediatric diseases caused by HCD. Methods: Forty specific pathogen-free (SPF)-grade Sprague-Dawley (SD) rats were randomly allocated into six groups: normal control 1 (NC1), normal control 2 (NC2), normal control 3 (NC3), high-calorie diets model (M), fecal microbe transplantation treatment (FMTT), and Medilac-Vita (MV) groups. Antibiotic intervention simulated the state of antibiotic-treated rats, and a specialized diet was used to replicate the HCD model. Based on group assignments, rats received a normal diet bacterial solution, normal saline enema, or MV. Clinical characteristics and colonic morphology were observed, while changes in gut microbiota, SCFAs, GPR43, and IL-18 were assessed using 16SrDNA, gas chromatography-mass spectrometry (GC-MS), hematoxylin-eosin (HE), immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA), respectively. Results: FMT effectively restored the gut microbiota of antibiotic-induced rats. In the HCD-induced rats, FMTT significantly alleviated the pathological state and increased alpha indices and beta distances (p < 0.05). Furthermore, significant alterations in the relative abundances of gut bacterial genera associated with SCFAs production were observed. FMTT increased SCFA content in feces, especially acetic acid (p < 0.05). Notably, downstream pathways related to SCFAs, such as GPR43-IL-18, were modulated by FMT in HCD-induced rats (p < 0.05). Recognizing the crucial role of gut microbiota in SCFAs metabolism, a co-occurrence network among the Lactobacillaceae and SCFAs-GPR43-IL-18 was constructed. Conclusion: The Lactobacillaceae-acetic acid-GPR43-IL-18 pathway emerges as a potential biological basis for the pathological state of HCD-induced rats. FMT exhibits corrective properties by influencing this pathway.