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Disturbances in gut microbiota and its metabolites have been observed in individuals with depression and animal models, suggesting a link between depression and disrupted gut microbiota, as well as impaired neural communication (Liu L

For animals, B12 oral supplements are not ideal, as it would require taking large quantities for the right amount to be absorbed

One disadvantage of the above described techniques for nose-to-brain drug delivery is that drugs are delivered to the entire brain unspecifically, whereas most CNS diseases primarily affect certain brain regions or cell types