Extracellular Vesicles from probiotics mediated Walnut green husk polysaccharide alleviates ochratoxin-A-induced cognitive impairment via tryptophan metabolism mediated AQP1/Wnt signaling pathway

Ochratoxin A (OTA) is a serious global food safety hazard that risks human health. Previous research showed that Walnut green husk polysaccharides (WGP) improve intestinal barrier function and microbiota disturbances caused by OTA. This study investigates WGP's ability to prevent OTA-induced cognitive impairments and its protective mechanisms. OTA exposure led to cognitive impairments and inhibited hippocampal neurogenesis, effects that were reversed by WGP supplementation. WGP corrected OTA-induced gut dysbiosis, including the decreased abundance of Lactobacillus johnsonii (L. john) and Akkermansia muciniphila (AKK), elevated proinflammatory factors, reduced neurotransmitter levels, and decreased fecal SCFA levels. The beneficial effects of WGP were negated by antibiotic treatment. Transplanting OTA-affected microbiota into normal mice reproduced the effects of OTA exposure, which were alleviated by transplanting microbiota from OTA+WGP-treated mice. Colonization with L. john and AKK reversed OTA-induced impairments, increasing 5-hydroxytryptamine (5-HT) and short-chain fatty acids (SCFA) levels. Additionally, extracellular vesicles (EVs) from L. john and AKK, as well as supplementation with 5-hydroxytryptophan (5-HTP) and SCFA, mitigated OTA-induced impairments. These findings suggest that WGP exerts neuroprotective effects against OTA-induced cognitive dysfunction through the microbiota-gut-brain axis by enhancing 5-HT and SCFA production, ameliorating cognitive impairment, and promoting hippocampal neurogenesis.