With the wide use of titanium dioxide nanoparticles (TiO(2) NPs) in food products, inflammatory bowel disease (IBD) was inevitably to ingest it. In this work, we daily administered TiO(2) NPs to mice, followed by dextran sulfate sodium (DSS)-drinking for 7 days to obtain the colitis model. Excitedly, shorten colon length, earlier and increased weigh body loss, higher disease activity index score, as well as disorganized pathological structure were observed in colitis mice with TiO(2) NPs exposure. Moreover, the significant changes in overproduction of inflammatory cytokines and oxidative injure were detected in colon. 16S rDNA sequencing results showed that TiO(2) NPs broke the balance of gut microbiota, including decreased alpha-diversity index, reduced the total operational taxonomic units (OTUs) number and altered the community distribution and compositions. To find the key bacterial regulator, we further analyzed the abundance change of differential species, found that the relative abundance of short-chain fatty acid (SCFAs)-producing bacteria (Muribaculaceae, Ruminococcus, Clostridia, etc.) noticeably reduced, while the relative abundance of pathogenic bacteria (Gastranaerophilaceae, Helicobacter, Escherichia-Shigella, etc.) dramatically augmented. The mutual cooperation of reduced SCFAs and elevated inflammatory factors induced the form of inflammation-oxidative cascade cycle. Our work highlighted the risk assessment of dietary nanoparticles on the IBD population and identified the key microbial regulators, looking forward to provide the target therapeutic strategies for IBD affected by environmental factors.