Nobiletin improves diphenoxylate-induced constipation and the accompanied depressive behavior disorders by regulating gut-SCFAs-brain axis

Prolonged constipation has been linked to depressive behaviors, with gut microbiota playing a crucial role. Nobiletin (NOB), a natural flavone, is reported for alleviating depressive behaviors, improving gut barrier function, and reducing neuroinflammation. This study explores how NOB alleviates constipation-induced depression in mice. NOB mitigates constipation symptoms, upregulates tight junction proteins, and prevents gut barrier damage. It also reduces depression and anxiety-like behaviors by inhibiting neuro-inflammation and preventing synaptic damage. NOB reshapes gut microbiota, increasing short-chain fatty acids (SCFAs) in mice feces and supplements SCFAs can also alleviate constipation-induced depression. In essence, NOB intake shows promise as a nutritional strategy to prevent constipation-induced depression via the gut-SCFAs-brain axis.