Studies have shown that the monocontamination of germ-free IL-1 receptor antagonist–deficient (IL1rn-/-) mice, which develop spontaneous arthritis due to excessive IL-1 signaling, with indigenous Lactobacillus bifidus resulted in rapid onset of arthritis that reached incidence rate and severity scores comparable to those recorded in non–germ-free mice (49). This evidence concerns the gene IL1RN and Arthritis.