Increased gut inflammation may induce bone loss due to chronic systemic inflammation.90 Patients with Crohn’s disease (CD) exhibit increased levels of proinflammatory cytokines, including IL-6, TNFα, IL-1 and RANKL, and benefit from anti-TNFα therapy targeting gut inflammation and bone density.6 These observations are in line with our data and further suggest that the gut may be the origin of the systemic chronic inflammation inducing bone loss in TLR9−/− mice. The gene discussed is TNF; the disease is Crohn disease.