Rapid and relaying deleterious effects of a gastrointestinal pathogen, Citrobacter rodentium, on bone, an extra-intestinal organ

Enteropathogenic infections cause pathophysiological changes in the host but their effects beyond the gastrointestinal tract are undefined. Here, using Citrobacter rodentium infection in mouse, which mimics human diarrheal enteropathogenic Escherichia coli, we show that gastrointestinal infection negatively affects bone remodeling, leading to compromised bone architecture. Transmission of infection through fecal-oral route from Citrobacter rodentium-infected to non-infected mice caused bone loss in non-infected cage mates. Mice with B cell deficiency (Igh6-/- mice) failed to clear C. rodentium infection and exhibited more severe and long-term bone loss compared to WT mice. Unbiased cytokine profiling showed an increase in circulating tumor necrosis factor α (TNFα) levels following Citrobacter rodentium infection, and immunoneutralization of TNFα prevented infection-induced bone loss completely in WT and immunocompromised mice. These findings reveal rapid, relaying, and modifiable effects of enteropathogenic infections on an extraintestinal organ-bone, and provide insights into the mechanism(s) through which these infections affect extraintestinal organ homeostasis.