Ulcerative colitis (UC) is a long-term digestive disease that can also affect the brain, leading to problems with thinking and memory. Researchers have explored how a specific type of gut bacteria, Akkermansia muciniphila, can help. In an experiment with mice, they found that tiny particles from this bacteria improved both gut health and cognitive function. The treatment not only eased symptoms of colitis but also helped restore memory and learning abilities. The study showed that these particles can repair gut barriers, reduce inflammation in the brain, and balance important brain chemicals. Overall, this research suggests that Akkermansia muciniphila could be a promising new way to treat both gut and brain issues linked to colitis.
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Ulcerative colitis (UC) is a chronic inflammatory bowel disease with systemic manifestations, including cognitive impairment linked to gut‒brain axis dysregulation. While probiotic therapies show promise, their mechanisms in mitigating neuropsychiatric comorbidities remain unclear. Here, we investigated the therapeutic potential of Akkermansia muciniphila-derived extracellular vesicles (AmEVs) in a murine model of dextran sulfate sodium (DSS)-induced colitis and associated cognitive deficits. AmEVs administration significantly alleviated colitis severity, as evidenced by improved weight retention, reduced disease activity index scores, and colon length restoration. Concurrently, AmEVs reversed colitis-driven cognitive impairments, restoring Y-maze and novel object recognition performance to baseline levels. Mechanistically, AmEVs repaired intestinal and blood‒brain barrier integrity by upregulating tight junction proteins, suppressed neuroinflammation via reduced hippocampal pro-inflammatory cytokines, and inhibited microglial/astrocyte activation. Gut microbiota analysis revealed that AmEVs-mediated enrichment of beneficial Bifidobacterium and suppression of pathogenic Bacteroides and Mucispirillum, alongside restored short-chain fatty acid (SCFA) production. Crucially, AmEVs bidirectionally regulated tryptophan metabolism, reducing colonic serotonin (5-HT) overproduction while restoring hippocampal 5-HT levels and 5-HT1A receptor expression. This was accompanied by enhanced synaptic plasticity and BDNF upregulation in the hippocampus. Proteomic and biodistribution studies confirmed AmEVs' delivery of metabolic regulators to hippocampal neurons, including the key protein Amuc_1100,directly enhancing 5-HT production in vitro. Our findings establish AmEVs as a multifaceted therapeutic agent that concurrently resolves gut inflammation and cognitive deficits via gut-brain axis modulation, offering novel strategies for IBD-related neuropsychiatric comorbidities. Further research is warranted to validate critical vesicular components and optimize clinical translation.
