BackgroundCoccidiosis is an intestinal parasitic disease caused byEimeriaprotozoa, which endangers the health and growth of animals, and causes huge economic losses to the poultry industry worldwide every year. Studies have shown that poultry gut microbiota plays an important role in preventing the colonization of pathogens and maintaining the health of the host. Coccidia infection also affects host gene expression. However, the underlying potential relationship between gut microbiome and host transcriptome duringE. tenellainfection in chickens remain unclear.MethodsIn this study, metagenomic and transcriptome sequencing were applied to identify microbiota and genes in cecal contents and cecal tissues of infected (JS) and control (JC) chickens on day 4.5 postinfection (pi), respectively.ResultsFirst, microbial sequencing results of cecal contents showed that the abundance ofLactobacillus, Roseburiasp. andFaecalibacteriumsp decreased significantly afterE. tenellainfection (P< 0.05), while the abundance ofAlistipesandPrevotella pectinovoraincreased significantly (P< 0.05). Second, transcriptome sequencing results showed that a total of 434 differentially expressed mRNAs were identified, including 196 up-regulated and 238 down-regulated genes. These differentially expressed genes related to inflammation and immunity, such asGAMA, FABP1, F2RL1 and RSAD2, may play an important role in the process of host resistance to coccidia infection. Functional studies showed that the enriched pathways of differentially expressed genes included the TGF-beta signaling pathway and the ErbB signaling pathways. Finally, the integrated analysis of gut microbiome and host transcriptome suggested thatPrevotella pectinovoraassociated withFABP1,Butyricicoccusporcorum andColidextribactersp. associated withRSAD2were involved in the immune response uponE. tenellainfection.ConclusionIn conclusion, this study provides valuable information on the microbiota and key immune genes after chickenE. tenellainfection, with the aim of providing reference for the impact of coccidia infection on cecal microbiome and host.