Microbiota regulate innate immune signaling and protective immunity against cancer

Changsheng Xing, Mingjun Wang, Adebusola A. Ajibade, Peng Tan, Chuntang Fu, Lang Chen, Motao Zhu, Zhao Zhe Hao, Junjun Chu, Xiao Yu, Bingnan Yin, Jiahui Zhu, Wan Jou Shen, Tianhao Duan, Helen Y. Wang, Rong Fu Wang

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)959-974.e7
JournalCell Host and Microbe
Volume29
Issue number6
DOIs
StatePublished - Jun 9 2021

Keywords

  • Bacteroides sp. D20
  • Odoribacter splanchnicus
  • TAK1 signaling
  • Th17 cells
  • acute colitis
  • colon cancer
  • innate immunity
  • microbiota

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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