Fig. 7

Schematic strategy for DI’s role in improving cognitive impairment induced by HF diet via the gut-brain axis. DI supplementation is proposed to alleviate the macrophage infiltration, upregulate the expression of IL-23, IL-22, and Reg3γ in the colon (1), which jointly prevent HF diet-induced microbiome shift (2). Then, the rescued gut microbiome can produce more butyrate and propionate to repair the compromised intestinal integrity (3). This decreases the levels of pro-inflammatory mediators in the blood and the brain, thereby mitigating neuroinflammation (4) and synaptic damage in the hippocampus (5), which ultimately improves cognition (6). Therefore, the supplementation of DI has a beneficial impact on cognition via the gut-brain axis. Red arrows represent altered indices induced by the HF diet, while green arrows show the protective effects of DI in HF diet-fed mice