Impact of in the gastrointestinal tract on natural killer cells.

BACKGROUND

Gut microbial dysbiosis contributes to the development and progression of colorectal cancer (CRC). Natural killer (NK) cells are involved in early defense mechanisms to kill infective pathogens and tumor cells by releasing chemokines and cytokines. To better understand the relationship between the gut microbiome and CRC, it was hypothesized here that a high abundance of () in the gastrointestinal tract could cause reduced NK cell activity.

AIM

To identify associations between gastrointestinal tract levels and NK cell activity.

METHODS

experiments were performed on NK cells treated with and to identify the effects of gut microbiome species on NK cells. Following 24 and 48 h of treatment, NK cell counts were measured. In parallel studies, C57BL/6 mice were given broad-spectrum antibiotics in their drinking water to reduce resident gut flora. After 3 wk, the mice received the various bacterial species or phosphate-buffered saline (PBS) oral gavage every 2 d for 6 wk. At the study end, blood samples were acquired to perform NK cell activity assessment and cytokine analysis. Intestinal tissues were collected and analyzed immunohistochemistry (IHC).

RESULTS

The data show that after 3 wk of broad-spectrum antibiotic treatment, levels of total bacteria and were markedly decreased in mice. Gavage of significantly decreased NK cell activity relative to the activities of cells from mice treated with antibiotics only and PBS. The administration of decreased the proportion of NK46 cells based on IHC staining and increased the production of interleukin-1β and tumor necrosis factor-α.

CONCLUSION

High levels of in the gastrointestinal tract reduced NK cell activity in mice, and the decrease in NK cell activity might be affected by increased pro-inflammatory cytokines after treatment