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Cigarettes and IBD: it’s in your genes
Yadav P, Ellinghaus D, Rémy G, et al. Genetic factors interact with tobacco smoke to modify risk for inflammatory bowel disease in humans and mice. Gastroenterology 2017;153:550–565.
The relationship between smoking and IBD risk is unclear. Gene–smoking interactions in IBD were explored at a genome-wide level in this paper using data from the International IBD Genetics Consortium. Immunochip custom array data from 20 000 IBD cases were compared with control cases in a meta-analysis of smokers versus non-smokers. Sixty-four single nucleotide polymorphisms (SNPs) were identified for which the associated risk of IBD was affected by smoking. Nearly half of these SNPs were close to SNPs known to be related to IBD, and many were located near genes linked with mucosal barrier regulation and immune response. Twenty SNPs were within the human leucocyte antigen region at 6p21, so the effect on adaptive immunity may be an explanation for the gene–smoking interaction. Seven SNPs interacted with smoking in opposite directions in Crohn’s disease and UC. There was also a contrast between former, ever and current smokers. Two genes identified as potentially interacting with smoking, Il10 and Nod2, were evaluated in genetic knockout mouse models exposed to smoke in ventilated smoking chambers, equivalent to five cigarettes per day for 8 weeks. Il10-deficient mice developed accelerated colitis as well as ileitis. Nod2-deficient mice developed ileitis. In wild type mice exposed to smoke, there was no sign of IBD. Hence, there is a protective role of Il10 and Nod2 in response to smoking and may have a role in disease location. In summary, the effect of smoking in the pathogenesis of IBD depends on patient-specific genetic variants.
Intestinal fungal dysbiosis and systemic fungal translocation promote the progression of alcohol-related liver disease
Yang AM, Inamine T, Hochrath K, et al. Intestinal fungi contribute to development of alcoholic liver disease. J Clin Invest 2017;127:2829–41.
Alterations in the …
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