The microbiota plays a crucial role in experimental models of inflammatory bowel disease, but the exact mechanisms of its effects are unknown. These studies took two molecular approaches to this question. The first used amplification of the 16s ribosomal DNA to define microbial diversity in the colon. Although there were differences in colitic and non-colitic mice, we could not determine whether this was primary or secondary to the disease. The second approach used serologic expression cloning to identify the microbial proteins stimulating the pathogenic immune response. Previously unknown microbial flagellins were the dominant cluster of antigens identified. About half of the sera from patients with Crohn's disease have IgG antibodies to these flagellins. © 2006 New York Academy of Sciences.