Dendrobium officinale polysaccharide attenuates cognitive impairment in circadian rhythm disruption mice model by modulating gut microbiota

Dendrobium officinale polysaccharide (DOP) has received an increasing amount of attention as it could alleviate AD-related cognitive impairment via the regulation of microglial activation. However, the modulatory mechanism of DOP on circadian rhythm disruption (CRD) and related cognitive impairment needs further investigation. In our study, the circadian rhythm disruption mice showed a deficit in recognition and spatial memory. DOP treatment reshaped the perturbation of gut microbiota caused by CRD, including up-regulated the abundance of Akkermansia and Alistipes, down-regulated the abundance of Clostridia. In addition, DOP restored histopathological changes, reduced inflammatory cells infiltration and strengthened mucosal integrity. Mechanistically, DOP ameliorated intestinal barrier dysfunction by up-regulating tight junction protein expression, which in turn improved the invasion of lipopolysaccharide to blood and brain. The change of these contributes to inhibiting the NF-κB activation and neuroinflammation, and thus attenuating hippocampus neuronal damage and the deposition of Aβ. Meanwhile, our results revealed that DOP could reverse the levels of metabolites derived related to cognitive function improvement, and these metabolites were closely associated with the key microbiota. Therefore, we speculated that DOP has the potential to provide neuroprotection against cognitive impairment by modulating the gut microbiota.