Route Connection: Mouth to Intestine in Colitis Naohiro Inohara  Cell Host & Microbe  Volume 22, Issue 6, Pages 730-731 (December 2017) DOI: 10.1016/j.chom.2017.11.012 Copyright © 2017 Terms and Conditions

Figure 1 Oral Cavity as a Potential Reservoir for Bacteria that Can Promote Intestinal Disease (A) The ability of Klebsiella strains to induce Th1 cells. Atarashi et al. (2017) use monocolonized germ-free (GF) mice and found Klebsiella as the predominant Th1 inducers among oral bacteria of Crohn’s disease patients. Analysis of knockout mice demonstrated the importance of MyD88-dependent IL-18 and TLR signaling for Klebsiella-mediated Th1 cell induction. Colonic epithelial cells and CD11b−CD103+ dendritic cells were also suggested to be possible sources of IL-18 and antigen presentation, respectively. The positive feedforward loop via IFNγR is also important for sustained induction of Th1 cells. Colonization of Klebsiella strains in mice lacking the immunosuppresive cytokine IL-10 resulted in increased Th1 cell numbers and also colitis, whereas wild-type mice exhibited only increased Th1 cell population, suggesting that the development of intestinal inflammation is dependent on host immune function. (B) Strain-specific effects on colitis and future directions. Atarashi et al. (2017) also demonstrated that individual Klebsiella pneumoniae strains differentially induced Th1 responses related to their genetic content, including the presence of fructose/galactitol, mannose, and long-chain fatty acid-related genes. Although it remains unclear how these genes affect Th1 induction and colitis susceptibility in immunodeficient hosts, these genes are distinct from those related to intra- and inter-species competitiveness. As Klebsiella has known drug resistance, strategies other than antibiotics may be required to limit its oral colonization and translocation into the intestine, such as oral microbiota transfer. Cell Host & Microbe 2017 22, 730-731DOI: (10.1016/j.chom.2017.11.012) Copyright © 2017 Terms and Conditions