Lycopene Regulates Intestinal Dysmotility and Behavioral Disorders via Regulating Enteric Neurons and Cholinergic system

Abstract

Gut dysmotility is a prevalent gastrointestinal disorder characterized by disrupted defecation and often accompanied by depression and anxiety. Lycopene (LYC) is a type of carotenoid with strong antioxidant and anti-inflammatory properties. However, the efficiency of LYC on gut dysmotility and related behavioral disorders remain elusive. Here, we found that 100 mg/kg/d LYC notably improved gut transit time and intestinal transit rate, and concurrently alleviated depression and anxiety-like behaviors in a diphenoxylate (Dip, 5 mg/kg/d)-induced constipated mouse model. LYC pretreatment enhanced gut barrier integrity and short-chain fatty acids (SCFAs) production, rebalanced gut microbiota homeostasis by enriching beneficial bacteria including Bifidobacterium, Akkermansia. Furthermore, LYC restored enteric neurons function manifested as increased HuC/D and Tuj1 expressions and balanced neurotransmitter. Brain transcriptomics results suggested that LYC regulated cholinergic synapse pathway and increased acetylcholine (Ach) content in the brain, which was associated with alleviation of neuroinflammation. Collectively, this study offered insights for dietary functional components-mediated nutritional strategies targeting gut dysmotility comorbid behavioral dysfunction.