Tissue-resident Lachnospiraceae family bacteria protect against colorectal carcinogenesis by promoting tumor immune surveillance

The intestinal microbiota plays an important role in colorectal cancer (CRC) progression. However, the effect of tissue-resident commensal bacteria on CRC immune surveillance remains poorly understood. Here, we analyzed the intratissue bacteria from CRC patient colon tissues. We found that the commensal bacteria belonging to the Lachnospiraceae family, including Ruminococcus gnavus (Rg), Blautia producta (Bp), and Dorea formicigenerans (Df), were enriched in normal tissues, while Fusobacterium nucleatum (Fn) and Pep-tostreptococcus anaerobius (Pa) were abundant in tumor tissues. Tissue-resident Rg and Bp reduced colon tumor growth and promoted the activation of CD8+ T cells in immunocompetent mice. Mechanistically, intra-tissue Rg and Bp degraded lyso-glycerophospholipids that inhibited CD8+ T cell activity and maintained the immune surveillance function of CD8+ T cells. Lyso-glycerophospholipids alone promoted tumor growth that was abrogated with Rg and Bp injection. Collectively, intratissue Lachnospiraceae family bacteria facilitate the immune surveillance function of CD8+ T cells and control colorectal cancer progression.

Automated summary

Gut microbiota plays a vital role in colorectal cancer progression, with tissue-resident commensal bacteria affecting CRC immune surveillance. This study identified specific bacteria in both normal and tumor colon tissues of CRC patients, showing an enrichment of Lachnospiraceae family in normal tissues and of Fusobacterium nucleatum and Pep-tostreptococcus anaerobius in tumor tissues. The tissue-resident Rg and Bp bacteria were found to inhibit colon tumor growth and enhance the activation of CD8+ T cells, promoting immune surveillance function. These bacteria degraded lyso-glycerophospholipids that inhibited CD8+ T cell activity, and their injection abrogated lyso-glycerophospholipid-induced tumor growth.