Microbiota regulate innate immune signaling and protective immunity against cancer

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 (Tak1(Delta M/Delta M)) yields complete resistance to chemical-induced colitis and CRC through microbiome alterations that drive protective immunity. Tak1(Delta M/Delta M) mice exhibit altered microbiota that are critical for resistance, with antibiotic-mediated disruption ablating protection and Taki m microbiota transfer conferring protection against colitis or CRC. The altered microbiota of Tak1(Delta M/Delta M) mice promote IL-1 beta and IL-6 signaling pathways, which are required for induction of protective intestinal Th17 cells and resistance. Specifically, Odoribacter splanchnicus is abundant in Tak1(Delta M/Delta M) 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.

Automated summary

The research revealed that mice lacking the immune signaling molecule TAK1 exhibited complete resistance to colitis and CRC through microbiome alterations. The altered microbiota in Tak1(Delta M/Delta M) mice promote IL-1 beta and IL-6 signaling pathways, which are necessary for inducing protective intestinal Th17 cells.