Dynamic association between gut microbiota succession and host metabolism: differential effects of antibiotic intervention duration on glucose and lipid metabolism in high-fat diet-induced obese mice

Abstract Background The gut microbiota plays a critical role in the onset and progression of obesity. Previous studies have indicated that antibiotic administration may influence host physiology and pathology by modulating the gut microbiota. However, whether different durations of antibiotic intervention lead to distinct patterns of microbiota succession, and how these patterns correlate with alterations in host metabolic phenotypes, remain to be fully elucidated. This study aimed to investigate the association between gut microbiota succession and host metabolic changes under different durations of antibiotic intervention, and to explore the underlying mechanisms from the perspectives of microbial community structure, microbial metabolites, and host inflammatory responses. Results Compared with the high-fat diet control group (FG), the long-term antibiotic intervention group (L-AFG) exhibited greater body weight gain and showed further dysregulation in adiposity, glucose metabolism, and inflammatory markers. In contrast, the short-term antibiotic intervention group (S-AFG) showed tendencies toward improvement in certain metabolic parameters, although most of these differences did not reach statistical significance relative to the FG. Microbiota analysis revealed that the L-AFG displayed the most severe gut dysbiosis, characterized by persistently low diversity, depletion of beneficial phyla (e.g., Bacteroidota), marked expansion of potential pathogens (particularly Escherichia-Shigella within Proteobacteria), and widespread suppression of short-chain fatty acid (SCFA) levels. In the S-AFG, trends toward enrichment of certain potentially beneficial genera (e.g., Coriobacteriaceae_UCG-002 and Blautia ) were observed, along with relatively favorable changes in inflammatory markers; however, the overall microbial community structure and SCFA levels remained generally similar to those of the FG. Conclusion The duration of antibiotic intervention is associated with alterations in gut microbiota succession patterns, host metabolism, and inflammatory phenotypes under high-fat diet conditions. Long-term antibiotic intervention may exacerbate gut dysbiosis and metabolic abnormalities, whereas short-term antibiotic intervention, despite not eliciting significant metabolic improvements, demonstrated greater potential for microbial restoration and relatively favorable inflammatory changes. These findings suggest that antibiotic exposure duration may be a key determinant of gut microbiota recovery trajectories and host metabolic responses; however, the causal relationships require further clarification through functional validation studies.