Transcriptomics Analysis Reveals the Immune Response Mechanism of Rabbits with Diarrhea Fed an Antibiotic-Free Diet

China officially promulgated the announcement of banning the use of antibiotics in the animal industry in 2020. However, the prohibition of antibiotics in the animal industry would reduce the feed conversion rate and increase the mortality of animals. In order to obtain information about the pathogenesis and host immune response of rabbits with diarrhea after being fed an antibiotic-free diet, we first analyzed the intestinal tissue sections of rabbits. Secondly, the gene expression differences of rabbit intestinal segments were analyzed by high-throughput sequencing. Our analysis identified 168, 593, 2069, 334, 321, and 1423 DEGs in the comparison groups S_Z (the duodenum of healthy rabbits) vs. S_B (diarrhea in the duodenum of rabbits), K_Z (healthy rabbit jejunum) vs. K_B (rabbits with diarrhea in the jejunum), H_Z (healthy rabbit ileum) vs. H_B (rabbits with diarrhea in the ileum), M_Z (healthy cecum of rabbits) vs. M_B (rabbits with diarrhea in the cecum), J_Z (healthy rabbit colon) vs. J_B (colon of rabbits with diarrhea), and Z_Z (healthy rabbit rectum) vs. Z_B (rectum of rabbits with diarrhea), respectively. The reproducibility and repeatability of the results were validated by RT-qPCR. Enrichment analyses of GO annotations and KEGG pathways revealed the host DEGs that are potentially related to acute inflammation, stress response, tissue dehydration, adaptive immune response, protein binding, activation of related enzymes, migration of immune cells, and so on. In this descriptive study, our findings revealed the changes in the host transcriptome expression profile after feeding an antibiotic-free diet and suggested that feeding an antibiotic-free diet alters the host's metabolic network and the expression of antiviral proteins, which provides a theoretical basis for further study on the immune response of animals fed an antibiotic-free diet.