@article{783adcc2733c4240bfe01880db2d3a82,
title = "Microbiota regulate innate immune signaling and protective immunity against cancer",
abstract = "Microbiota play critical roles in regulating colitis and colorectal cancer (CRC). However, it is unclear how the microbiota generate protective immunity against these disease states. Here, we find that loss of the innate and adaptive immune signaling molecule, TAK1, in myeloid cells (Tak1ΔM/ΔM) yields complete resistance to chemical-induced colitis and CRC through microbiome alterations that drive protective immunity. Tak1ΔM/ΔM mice exhibit altered microbiota that are critical for resistance, with antibiotic-mediated disruption ablating protection and Tak1ΔM/ΔM microbiota transfer conferring protection against colitis or CRC. The altered microbiota of Tak1ΔM/ΔM mice promote IL-1β and IL-6 signaling pathways, which are required for induction of protective intestinal Th17 cells and resistance. Specifically, Odoribacter splanchnicus is abundant in Tak1ΔM/ΔM mice and sufficient to induce intestinal Th17 cell development and confer resistance against colitis and CRC in wild-type mice. These findings identify specific microbiota strains and immune mechanisms that protect against colitis and CRC.",
keywords = "Bacteroides sp. D20, Odoribacter splanchnicus, TAK1 signaling, Th17 cells, acute colitis, colon cancer, innate immunity, microbiota",
author = "Changsheng Xing and Mingjun Wang and Ajibade, {Adebusola A.} and Peng Tan and Chuntang Fu and Lang Chen and Motao Zhu and Hao, {Zhao Zhe} and Junjun Chu and Xiao Yu and Bingnan Yin and Jiahui Zhu and Shen, {Wan Jou} and Tianhao Duan and Wang, {Helen Y.} and Wang, {Rong Fu}",
note = "Funding Information: We thank Michael Schneider (Baylor College of Medicine) for providing Tak1 flox/flox mice, Scott Durum (National Institutes of Health) for Il17-GFP + mice; Cynthia Sears (Johns Hopkins University) for providing NTBF; Wei Wang (MD Anderson Cancer Center) for histopathological scoring; Julian Hurdle (Texas A&M University) for anaerobic bacterial culture; Chen Qian, Xin Liu, Linfeng Li, Bo Ning, Qingtian Li, and Xilai Ding (Houston Methodist Research Institute) for technical advice; Changfu Yao (Cedars-Sinai Medical Center) and Pengfei Liu (Baylor College of Medicine) for scientific advice; Chongming Jiang, Huahui Ren, and Kaifu Chen (Houston Methodist Research Institute) for support on data analysis; Kalpana Mujoo and John Gilbert for scientific editing. This work was in part supported by grants from the NCI , NIH ( R01CA101795 and 1U54CA210181-01 ), and Department of Defense (DoD) CDMRP BCRP ( BC151081 ). Funding Information: We thank Michael Schneider (Baylor College of Medicine) for providing Tak1flox/flox mice, Scott Durum (National Institutes of Health) for Il17-GFP+ mice; Cynthia Sears (Johns Hopkins University) for providing NTBF; Wei Wang (MD Anderson Cancer Center) for histopathological scoring; Julian Hurdle (Texas A&M University) for anaerobic bacterial culture; Chen Qian, Xin Liu, Linfeng Li, Bo Ning, Qingtian Li, and Xilai Ding (Houston Methodist Research Institute) for technical advice; Changfu Yao (Cedars-Sinai Medical Center) and Pengfei Liu (Baylor College of Medicine) for scientific advice; Chongming Jiang, Huahui Ren, and Kaifu Chen (Houston Methodist Research Institute) for support on data analysis; Kalpana Mujoo and John Gilbert for scientific editing. This work was in part supported by grants from the NCI, NIH (R01CA101795 and 1U54CA210181-01), and Department of Defense (DoD) CDMRP BCRP (BC151081). R.-F.W. supervised the entire project. R.-F.W. and C.X. designed the experiments. C.X. and M.W. performed the experiments and collected the data. A.A.A. P.T. C.F. L.C. M.Z. J.C. X.Y. B.Y. W.-J.S. and T.D. provided assistances in some experiments. C.X. Z.-Z.H. J.Z. and H.Y.W. performed the data analyses. C.X. and R.-F.W. wrote the paper, with input from all other authors. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc. Copyright: Copyright 2021 Elsevier B.V., All rights reserved. Copyright {\textcopyright} 2021 Elsevier Inc. All rights reserved.",
year = "2021",
month = jun,
day = "9",
doi = "10.1016/j.chom.2021.03.016",
language = "English (US)",
volume = "29",
pages = "959--974.e7",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "6",
}