Current advances on gut microbiota have broadened our view on host-microbiota interactions. As a microbiota-targeted approach, the use of antibiotics has been widely adopted to explore the role of gut microbiota in vivo. Antibiotics can change the microbial composition, resulting in varied effects, depending on the antibiotic class, dosage, and duration. Antibiotic intervention in early life leads to life-long phenotype alterations, including obesity. Antibiotic-induced changes in gut microbiota affect the epithelial utilization of both macronutrients (e.g., amino acids) and micronutrients (e.g., copper, vitamin E) and the redox homeostasis. Of particular interest is the regulation of gut anaerobiosis and aerobiosis by oxygen availability, which is closely related to epithelial metabolism. Additionally, antibiotic interventions enable to identify novel roles of gut microbiota in gut-liver axis and gut-brain axis. Indigenous antimicrobial molecules are produced by certain microbes, and they have the potential to affect function through eliciting changes in the gut microbiota. This review discusses at length these findings to gain a better and novel insight into microbiota-host interactions and the mechanisms involved.