The tumor suppressor Tip60 inhibits TOR signaling in response to the microbiota to promote autophagy and enterocyte differentiation

Blocking Tip60 in enterocytes results in microbial penetration of the intestinal barrier, accumulation of undifferentiated enterocytes, and a failure of the acidic region of the MMG to develop. We previously showed that Tip60 controls innate immune signaling in enteroendocrine cells in response to microbial acetate. This assigns two additional innate immune functions to Tip60, namely destruction of intracellular bacteria via xenophagy and differentiation of the acid-producing cells of the MMG.

Because the fermentation pathways of microbiota are highly conserved as is the Tip60 lysine acetyltransferase and AKT/PI3K/mTOR signaling, we propose that a similar process may tie the intestinal microbiota, Tip60, and mTOR to each other and to the intestinal innate immune response and oncogenesis.