@article{35b19eb316774f0d9bd28ee877c08bc1,
title = "Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation",
abstract = "Intestinal colonization by bacteria of oral origin has been correlated with several negative health outcomes, including inflammatory bowel disease. However, a causal role of oral bacteria ectopically colonizing the intestine remains unclear. Using gnotobiotic techniques, we show that strains of Klebsiella spp. isolated from the salivary microbiota are strong inducers of T helper 1 (TH1) cells when they colonize in the gut. These Klebsiella strains are resistant to multiple antibiotics, tend to colonize when the intestinal microbiota is dysbiotic, and elicit a severe gut inflammation in the context of a genetically susceptible host. Our findings suggest that the oral cavity may serve as a reservoir for potential intestinal pathobionts that can exacerbate intestinal disease.",
author = "Koji Atarashi and Wataru Suda and Chengwei Luo and Takaaki Kawaguchi and Iori Motoo and Seiko Narushima and Yuya Kiguchi and Keiko Yasuma and Eiichiro Watanabe and Takeshi Tanoue and Thaiss, {Christoph A.} and Mayuko Sato and Kiminori Toyooka and Said, {Heba S.} and Hirokazu Yamagami and Rice, {Scott A.} and Dirk Gevers and Johnson, {Ryan C.} and Segre, {Julia A.} and Kong Chen and Kolls, {Jay K.} and Eran Elinav and Hidetoshi Morita and Xavier, {Ramnik J.} and Masahira Hattori and Kenya Honda",
note = "K.A. and K.H. acknowledge funding from the Uehara Memorial Foundation, the Takeda Science Foundation, the Mitsubishi Foundation, Core Research for Evolutionary Medical Science and Technology, and Leading Advanced Projects for Medical Innovation, a program of the Japan Agency for Medical Research and Development. C.L. and R.J.X. acknowledge funding from the U.S. NIH (grants DK043351 and DK92405), the Helmsley Charitable Trust, and the Crohn{\textquoteright}s & Colitis Foundation. We thank P. Wilmes, J. Baginska, M. Wakazaki, O. Ohara, and Y. Arakawa for their technical support and P. Burrows for helpful comments. M.H., H.M., and Y.K. conceived the research and performed initial experiments; K.H. planned experiments, analyzed data, and wrote the manuscript together with K.A., C.L., and R.J.X.; K.A., T.K., S.N., Y.K., I.M., K.Y., E.W., T.T., and C.A.T performed gnotobiotic studies, immunological analyses, and bacterial cultures; C.L., D.G., R.C.J., J.S., R.J.X., E.E., W.S., H.S.S., and M.H. performed bacterial sequence and microbiome analyses; M.S., K.T., and S.N. performed EM analyses; H.Y. provided clinical samples; and K.C., J.K.K., and S.A.R. provided essential materials and contributed to data discussions. J.K.K. is a recipient of Public Health Service grant R37 HL079142. K.H. is a scientific advisory board member of Vedanta Biosciences. All data and code to understand and assess the conclusions of this research are available in the main text, the supplementary materials, and the indicated repositories. Sequences of the genome of Klebsiella spp. and the 16S rRNA sequence data set are deposited in the DNA Data Bank of Japan under accession numbers PRJDB5883-5886 and PRJDB5967, respectively. The raw and processed RNA-seq data are deposited in the National Center for Biotechnology Information{\textquoteright}s Gene Expression Omnibus under accession number GSE23056. Klebsiella strains are available under a material transfer agreement with Keio University.",
year = "2017",
month = oct,
day = "20",
doi = "https://doi.org/10.1126/science.aan4526",
language = "الإنجليزيّة",
volume = "358",
pages = "359--365",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6361",
}