Increasing evidence from the home environment indicates that indoor microbiome exposure is associated with asthma development. However, indoor microbiome composition can be highly diverse and dynamic, and thus current studies fail to produce consistent results. Chinese university dormitories are special high-density dwellings with similar building and occupants characteristics, which facilitate to disentangle the complex interactions between microbes, environmental characteristics and asthma. Settled air dust and floor dust was collected from 87 dormitory rooms in Shanxi University. Bacterial communities were characterized by 16S rRNA amplicon sequencing. Students (n = 357) were surveyed for asthma symptoms and measured for fractional exhaled nitric oxide (FeNO). Asthma was not associated with the overall bacterial richness but associated with specific phylogenetic classes. Taxa richness and abundance in Clostridia, including Ruminococcus, Blautia, Clostridium and Subdoligranulum, were positively associated with asthma (p < 0.05), and these taxa were mainly derived from the human gut. Taxa richness in Alphaproteobacteria and Actinobacteria were marginally protectively associated with asthma, and these taxa were mainly derived from the outdoor environment. Bacterial richness and abundance were not associated with FeNO levels. Building age was associated with overall bacterial community variation in air and floor dust (p < 0.05), but not associated with the asthma-related microorganisms. Our data shows that taxa from different phylogenetic classes and derived habitats have different health effects, indicating the importance of incorporating phylogenetic and ecological concepts in revealing patterns in the microbiome asthma association analysis.