Caffeic Acid Alleviates Chronic Sleep Deprivation-Induced Intestinal Damage by Inhibiting the IMD Pathway in Drosophila.

Background: Sleep is vital for maintaining the health of the organism. Chronic sleep deprivation (CSD) is a key contributor to significant health risks, including the induction of gastrointestinal disorders. However, the mechanism of CSD caused intestinal damage remains unclear.

Methods: Drosophila melanogaster as an in vivo model was used to investigate the mechanism of CSD-induced intestinal injury, as well as the ameliorative effect of caffeic acid.

Results: CSD resulted in reduced survival and severely affected intestinal homeostasis in flies, as evidenced by disruption of intestinal acid-base homeostasis, increased feeding, increased intestinal permeability and shortened intestinal length. Meanwhile, the expressions of the immune deficiency (IMD) pathway-related genes PGRP-SB1, Dpt, AttA, AttB and Mtk were significantly up-regulated in the intestine of CSD flies. On the other hand, Caffeic acid supplementation restored intestinal acid-base homeostasis and intake, while improving intestinal barrier permeability and intestinal length, and effectively reducing intestinal damage. In addition, administration of caffeic acid decreased the expressions of PGRP-SB1, Dpt, AttA and Mtk genes in the CSD flies gut.

Discussion: These results suggested that CSD could disrupt gut homeostasis in adult flies by overactivating the IMD pathway, while Caffeic acid has an obvious protective role on the gut homeostasis.