Rapid and Relaying Deleterious Effects of a Gastrointestinal Pathogen, , 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 infection in mouse, which mimics human diarrheal enteropathogenic , we show that gastrointestinal infection negatively affects bone remodeling, leading to compromised bone architecture. Transmission of infection through fecal-oral route from -infected to non-infected mice caused bone loss in non-infected cage mates. Mice with B cell deficiency (-/- mice) failed to clear 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 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.