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Background: Cleft palate (CP) patients have a higher prevalence of oral and respiratory tract bacterial infections than the general population. Nevertheless, characteristics of bacterial differences induced by CP-related anatomical heterogeneity are unknown. Methods: In this study, we systematically described the characteristics of bacteria in the oral and nasal niches in healthy children, CP children, healthy adolescents, CP adolescents, and postoperative adolescents by 454-pyrosequencing technology (V3–V6) to determine bacterial differences induced by CP. Results: Due to the CP-induced variations in spatial structure, the early establishment of microecology in CP children was different from that in healthy children. Nasal bacterial composition showed greater changes than in the saliva. Moreover, such discrepancy also appeared in CP and postoperative adolescents who had even undergone surgery > 10 years previously. Interestingly, we found by Lefse analysis that part of bacterial biomarkers in the nasal cavity of CP subjects was common oral flora, suggesting bacterial translocation between the oral and nasal niches. Therefore, we defined the oral–nasal translocation bacteria as O-N bac. By comparing multiple groups, we took the intersection sets of O-N bacs selected from CP children, CP adolescents, and postoperative adolescents as TS O-N bacs with time–character, including Streptococcus, Gemella, Alloprevotella, Neisseria, Rothia, Actinomyces, and Veillonella. These bacteria were at the core of the nasal bacterial network in CP subjects, and some were related to infectious diseases. Conclusions: CP would lead to significant and long-term differences in oral and nasal flora. TS O-N bacs migrating from the oral to the nasal might be the key stone causing nasal flora dysbiosis in the CP patients.