Mucosal Immunity

Some gut conditions, such as inflammatory bowel disease (IBD), ulcerative colitis, and Crohn's disease (CD), are associated with imbalances in the gut microbe community. The causes of these intractable diseases have been difficult to discern. Atarashi et al. took samples from the mouths of IBD and CD patients and inoculated the extracted bacteria into germ-free mice (see the Perspective by Cao). Some of the inoculated mice showed strong proliferation of T helper 1 cells associated with the establishment of oral Klebsiella species in the colon. Klebsiella can be resistant to multiple antibiotics and are able to replace normal colon microbes after antibiotic therapy. Now we know that they probably originate from the mouth and could potentially contribute to bowel disease.

Science , this issue p. [359][1]; see also p. [308][2]

[1]: /lookup/doi/10.1126/science.aan4526
[2]: /lookup/doi/10.1126/science.aap9298

Pathogenic infection has been implicated in the chronic inflammation seen in inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn's disease. Yang et al. show that recurrent, low-level, and fully resolving Salmonella enterica Typhimurium (ST) infections can precipitate severe colonic inflammation in mice. ST-induced TLR4 activation resulted in increased neuraminidase 3 (Neu3) production and activity in the duodenum. This led to intestinal alkaline phosphatase (IAP) desialylation and degradation. IAP deficiency caused a marked increase in commensal bacteria-generated lipopolysaccharide-phosphate in the colon, provoking inflammation. Treatment with calf IAP or the antiviral drug zanamivir (which inhibits Neu3 activity) prevented this inflammatory cascade. This pathway may serve as an effective target for future human IBD therapies.

Science , this issue p. [eaao5610][1]

[1]: /lookup/doi/10.1126/science.aao5610

IL-19, a member of the IL-10 cytokine family that signals through the IL-20 receptor type I (IL-20Rα:IL-20Rβ), is a cytokine whose function is not completely known. In this article, we show that the expression of IL19 in biopsies of patients with active ulcerative colitis was increased compared with patients with quiescent ulcerative colitis and that colitis was attenuated in IL-19–deficient mice. The disruption of the epithelial barrier with dextran sodium sulfate leads to increased IL-19 expression. Attenuated colitis in IL-19–deficient animals was associated with reduced numbers of IL-6–producing macrophages in the inflamed colonic lamina propria. Microbial-driven expression of IL-19 by intestinal macrophages may contribute to the pathogenesis of inflammatory bowel disease.