Accumulating evidence highlights that gut microbiota dysbiosis and subsequent peripheral and central neuroinflammation along the gut-brain axis are critical contributors to the initiation and progression of cognitive impairment. Most existing avocado-related neuroprotective studies focus on avocado oil rich in unsaturated fatty acids, whereas few investigations explore the efficacy of whole-fruit avocado freeze-dried powder retaining water soluble bioactive substances such as polyphenols and dietary fiber. The present study aimed to clarify whether avocado freeze-dried powder could alleviate scopolamine-triggered cognitive dysfunction and further reveal its underlying gut-brain axis-related mechanism. In this study, scopolamine was administrated to establish a mouse cognitive impairment model, followed by intragastric intervention with low-and high-dose avocado freeze-dried powder. Behavioral tests were performed to evaluate learning and memory capacity, and related mechanistic studies were conducted. Avocado freeze-dried powder intervention significantly ameliorated scopolamine‑induced cognitive impairment, while reshaping the dysbiotic gut microbiota (increasing the abundance of beneficial bacterial genera and suppressing the expansion of pro‑inflammatory taxa), restoring intestinal barrier integrity, reducing serum IL‑1β and LPS levels, and thereby inhibiting microglial overactivation and neuroinflammation. The low-dose intervention was more effective in enriching beneficial bacteria and enhancing microbial diversity, whereas the high-dose intervention exhibited greater advantages in restoring intestinal barrier integrity and suppressing the expansion of pro-inflammatory taxa. Collectively, avocado freeze-dried powder ameliorates scopolamine-induced cognitive impairment via modulating gut microbiota, repairing intestinal barrier and blocking gut-derived inflammation transmission to suppress central neuroinflammation. This work provides experimental support for developing whole-avocado-derived dietary supplements against cognitive disorders and makes up for the research deficiency dominated by avocado oil in previous reports.

Avocado Freeze-dried Powder, Cognitive Impairment, Gut-brain Axis, Intestinal Barrier, Neuroinflammation