Abstract
There is a bidirectional relationship between inflammatory bowel disease (IBD) and depression/anxiety. Emerging evidences indicate that the liver may be involved in microbiota-gut-brain axis. This experiment focused on the role of melatonin in regulating the gut microbiota and explores its mechanism on dextran sulphate sodium- (DSS-) induced neuroinflammation and liver injury. Long-term DSS-treatment increased lipopolysaccharide (LPS), proinflammation cytokines IL-1β and TNF-α, and gut leak in rats, breaking blood-brain barrier and overactivated astrocytes and microglia. Ultimately, the rats showed depression-like behavior, including reduction of sucrose preference and central time in open field test and elevation of immobility time in a forced swimming test. Oral administration with melatonin alleviated neuroinflammation and depression-like behaviors. However, melatonin supplementation did not decrease the level of LPS but increase short-chain fatty acid (SCFA) production to protect DSS-induced neuroinflammation. Additionally, western blotting analysis suggested that signaling pathways farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF 15) in gut and apoptosis signal-regulating kinase 1 (ASK1) in the liver overactivated in DSS-treated rats, indicating liver metabolic disorder. Supplementation with melatonin markedly inhibited the activation of these two signaling pathways and its downstream p38. As for the gut microbiota, we found that immune response- and SCFA production-related microbiota, like Lactobacillus and Clostridium significantly increased, while bile salt hydrolase activity-related microbiota, like Streptococcus and Enterococcus, significantly decreased after melatonin supplementation. These altered microbiota were consistent with the alleviation of neuroinflammation and metabolic disorder. Taken together, our findings suggest melatonin contributes to reshape gut microbiota and improves inflammatory processes in the hippocampus (HPC) and metabolic disorders in the liver of DSS rats.
Highlights
Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a chronic inflammatory disease that negatively affects the life quality of patients
Through longitudinal follow-up trials, they found that mental disease may be associated with poor prognosis of IBD and that intestinal inflammatory activity is related to the development of mental disorders [8,9,10]
By sequencing the 16S rRNA gene of rat feces, we found that Lactobacillus and Clostridium, immune-modulating, short-chain fatty acid (SCFA), and bile acid production microbiota may serve as a potential mechanism
Summary
Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a chronic inflammatory disease that negatively affects the life quality of patients. More than 30% of IBD patients were accompanied with mental disorders, including anxiety and depression [3]. Chronic diseases can lead to psychological disorders along with interpersonal relationships, family, work, and social stress [4, 5]. Oxidative Medicine and Cellular Longevity physical dysfunction, which in turn leads to immunosuppression, gut permeability, and other inflammation changes that may eventually result in chronic diseases, including IBD [6, 7]. There is a bidirectional relationship between IBD and mental disorders [11] These bidirectional brain-gut pathways have been reported to play a key role in functional gastrointestinal disorders such as IBS and functional dyspepsia [12, 13]. Stimulation of stress, anxiety, and depression can increase the burden on patients with IBD [14], there is still controversy between stress and IBD [15]
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