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Melatonin, autophagy and intestinal bowel disease. Talero Elena,Garcia-Maurino Sofia,Motilva Virginia Current pharmaceutical design The intestinal epithelium forms a barrier against the intestinal contents and the wider environment, allowing entry of selected molecules for nutrition and programming of the mucosal immune system, but excluding toxins and most microorganisms. Many receptors and signalling pathways are coupled and implicated in the epithelial control and significant advances have been achieved in the understanding of the pathogenesis of inflammatory bowel disease (IBD) and in the introduction of biologics. However, not all of the patients respond and many lose their response. Data from experimental studies have documented that the pineal secretory product melatonin exerts important inmunoregulatory and antiinflammatory effects in different models of colitis. These actions have been associated to a variety of mechanisms, such as reduction of T cells number, modulation of macrophage activity, suppression of NFκB activity, inhibition of cell adhesion molecules and proinflammatory cytokines , suppression of COX-2 and iNOS levels and the consequent synthesis of PGE2 and NO, reduction of matrix metalloproteinase (MMP) -2 and -9 activity, and modulation of apoptosis. In addition, the beneficial effects of melatonin in IBD are related to its scavenger effect on free radicals and the activation of several antioxidant enzymes. However, only a small number of human studies report possible beneficial and also possible harmful effects of melatonin in case reports and clinical trials. There is a considerable bulk of information supporting the connection between autophagy and human diseases, including IBD, and although autophagy is actually considered more a pro-survival than a pro-death pathway, these two features of its action are relevant in human diseases, having therapeutic potential for both activators and inhibitors of autophagy. Some of the opposite effects than have been reported for melatonin in IBD could be related to the duality of its effects on autophagy, which itself can be beneficial or detrimental. In this review, new data for melatonin in IBD are discussed, trying to provide recent information of different molecular mechanism including the role of the autophagy regulation.
New paradigms in chronic intestinal inflammation and colon cancer: role of melatonin. Motilva Virginia,García-Mauriño Sofía,Talero Elena,Illanes Matilde Journal of pineal research In intestinal bowel disease (IBD), immune-mediated conditions exert their effects through various cells and proinflammatory mediators. Recent data support a participation of the endoplasmic reticulum stress and mitochondrial dysfunctions in IBD. Moreover, it is evident that chronic degenerative pathologies, including IBD, share comparable disease mechanisms with alteration in the autophagy mechanisms. Chronic inflammation in IBD exposes these patients to a number of signals known to have tumorigenic effects. This circuitry of inflammation and cancer modifies apoptosis and autophagy, and promotes cellular cycle progression, invasion, and angiogenesis. Melatonin has been shown as a specific antioxidant reducing oxidative damage in both lipid and aqueous cell environments. However, several studies provide further insight into the molecular mechanisms of melatonin action in the colon. In this line, recent data suggest that melatonin modulates autophagy and sirtuin activity. An anti-autophagic property of melatonin has been demonstrated, and it could contribute to its anti-oncogenic activity. Nevertheless, there is no information about whether antitumoral effects of melatonin on colon cancer are dependent on autophagy. Sirtuins have pleiotropic effects on cancer development, being reported both as facilitator and as suppressor of colon cancer development. Sirtuins and melatonin are connected through the circadian clock machinery, and melatonin seems able to correct the alterations in sirtuin activity associated with several pathological conditions. Autophagy and sirtuin activities are linked through 5'AMP-activated protein kinase (AMPK) activation, which switches on autophagy and increases sirtuin. The effect of melatonin on AMPK and the impact of this effect on IBD and colon cancer remain an open question. 10.1111/j.1600-079X.2011.00915.x
Melatonin, a promising supplement in inflammatory bowel disease: a comprehensive review of evidences. Mozaffari Shilan,Abdollahi Mohammad Current pharmaceutical design Inflammation and oxidative process are associated with inflammatory bowel disease (IBD). Regarding anti-inflammatory and antioxidant potentials, melatonin has been found beneficial in several experimental and clinical studies including inflammatory bowel disease (IBD). Our objective in this study is to review and evaluate all non-clinical and clinical studies on the efficacy of melatonin in IBD. All indexing databases were searched for inflammatory bowel disease' and 'melatonin' keywords, without time limit up to May 2011. Three clinical trials and fifteen non-clinical studies are reviewed and analyzed. The majority of these studies indicate that melatonin has a positive impact on IBD with no or negligible side effects. Such results have been mostly explained through free radical scavenging and diminishing inflammation. It is yet crucial to determine the efficacy of melatonin in combination with other established drugs in more clinical trials, not only for further confirmation of its efficacy, but also to investigate its possible side effects in longer durations of therapy.
Melatonin for the treatment of irritable bowel syndrome. Siah Kewin Tien Ho,Wong Reuben Kong Min,Ho Khek Yu World journal of gastroenterology Irritable bowel syndrome (IBS) is a common disorder characterized by recurrent abdominal pain or discomfort, in combination with disturbed bowel habits in the absence of identifiable organic cause. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced by the pineal gland and also large number by enterochromaffin cells of the digestive mucosa. Melatonin plays an important part in gastrointestinal physiology which includes regulation of gastrointestinal motility, local anti-inflammatory reaction as well as moderation of visceral sensation. Melatonin is commonly given orally. It is categorized by the United States Food and Drug Administration as a dietary supplement. Melatonin treatment has an extremely wide margin of safety though it may cause minor adverse effects, such as headache, rash and nightmares. Melatonin was touted as a potential effective candidate for IBS treatment. Putative role of melatonin in IBS treatment include analgesic effects, regulator of gastrointestinal motility and sensation to sleep promoter. Placebo-controlled studies in melatonin suffered from heterogeneity in methodology. Most studies utilized 3 mg at bedtime as the standard dose of trial. However, all studies had consistently showed improvement in abdominal pain, some showed improvement in quality of life of IBS patients. Melatonin is a relatively safe drug that possesses potential in treating IBS. Future studies should focus on melatonin effect on gut mobility as well as its central nervous system effect to elucidate its role in IBS patients. 10.3748/wjg.v20.i10.2492
Melatonin's role as a co-adjuvant treatment in colonic diseases: A review. Esteban-Zubero Eduardo,López-Pingarrón Laura,Alatorre-Jiménez Moisés Alejandro,Ochoa-Moneo Purificación,Buisac-Ramón Celia,Rivas-Jiménez Miguel,Castán-Ruiz Silvia,Antoñanzas-Lombarte Ángel,Tan Dun-Xian,García José Joaquín,Reiter Russel J Life sciences Melatonin is produced in the pineal gland as well as many other organs, including the enterochromaffin cells of the digestive mucosa. Melatonin is a powerful antioxidant that resists oxidative stress due to its capacity to directly scavenge reactive species, to modulate the antioxidant defense system by increasing the activities of antioxidant enzymes, and to stimulate the innate immune response through its direct and indirect actions. In addition, the dysregulation of the circadian system is observed to be related with alterations in colonic motility and cell disruptions due to the modifications of clock genes expression. In the gastrointestinal tract, the activities of melatonin are mediated by melatonin receptors (MT2), serotonin (5-HT), and cholecystokinin B (CCK2) receptors and via receptor-independent processes. The levels of melatonin in the gastrointestinal tract exceed by 10-100 times the blood concentrations. Also, there is an estimated 400 times more melatonin in the gut than in the pineal gland. Gut melatonin secretion is suggested to be influenced by the food intake. Low dose melatonin treatment accelerates intestinal transit time whereas high doses may decrease gut motility. Melatonin has been studied as a co-adjuvant treatment in several gastrointestinal diseases including irritable bowel syndrome (IBS), constipation-predominant IBS (IBS-C), diarrhea-predominant IBS (IBS-D), Crohn's disease, ulcerative colitis, and necrotizing enterocolitis. The purpose of this review is to provide information regarding the potential benefits of melatonin as a co-adjuvant treatment in gastrointestinal diseases, especially IBS, Crohn's disease, ulcerative colitis, and necrotizing enterocolitis. 10.1016/j.lfs.2016.11.031
Melatonin reprogramming of gut microbiota improves lipid dysmetabolism in high-fat diet-fed mice. Yin Jie,Li Yuying,Han Hui,Chen Shuai,Gao Jing,Liu Gang,Wu Xin,Deng Jinping,Yu Qifang,Huang Xingguo,Fang Rejun,Li Tiejun,Reiter Russel J,Zhang Dong,Zhu Congrui,Zhu Guoqiang,Ren Wenkai,Yin Yulong Journal of pineal research Melatonin has been shown to improve lipid metabolism and gut microbiota communities in animals and humans; however, it remains to know whether melatonin prevents obesity through gut microbiota. Here, we found that high-fat diet promoted the lipid accumulation and intestinal microbiota dysbiosis in mice, while oral melatonin supplementation alleviated the lipid accumulation and reversed gut microbiota dysbiosis, including the diversity of intestinal microbiota, relative abundances of Bacteroides and Alistipes, and functional profiling of microbial communities, such as energy metabolism, lipid metabolism, and carbohydrate metabolism. Interestingly, melatonin failed to alleviate the high-fat-induced lipid accumulation in antibiotic-treated mice; however, microbiota transplantation from melatonin-treated mice alleviated high-fat diet-induced lipid metabolic disorders. Notably, short-chain fatty acids were decreased in high-fat diet-fed mice, while melatonin treatment improved the production of acetic acid. Correlation analysis found a marked correlation between production of acetic acid and relative abundances of Bacteroides and Alistipes. Importantly, sodium acetate treatment also alleviated high-fat diet-induced lipid metabolic disorders. Taken together, our results suggest that melatonin improves lipid metabolism in high-fat diet-fed mice, and the potential mechanisms may be associated with reprogramming gut microbiota, especially, Bacteroides and Alistipes-mediated acetic acid production. Future studies are needed for patients with metabolic syndrome to fully understand melatonin's effects on body weight and lipid profiles and the potential mechanism of gut microbiota. 10.1111/jpi.12524
Effects of Melatonin on Intestinal Microbiota and Oxidative Stress in Colitis Mice. Zhu Dan,Ma Yong,Ding Sujuan,Jiang Hongmei,Fang Jun BioMed research international This study investigated the antioxidant capacity and intestinal bacteria community in a mouse model of DSS-induced colitis. Twenty mice were randomly assigned to two treatments: mice with colitis induced by 5% DSS (DSS group) and mice with colitis induced by 5% DSS that also received melatonin treatment (MEL group). The DSS group showed significantly less antioxidant capability than the MEL group, but the two groups did not differ significantly in terms of diversity index (Shannon and Simpson), bacterial culture abundance (Chao1 and ACE), and coverage (Good's coverage estimator). Bacteroidetes were the most abundant phylum in the DSS group (58.93%), followed by Firmicutes with 31.46% and Proteobacteria with 7.97%. In contrast, Firmicutes were the most abundant in the MEL group (49.48%), followed by Bacteroidetes with 41.63% and Proteobacteria with 7.50%. The results support the use of melatonin for prevention of intestinal bowel disease due to its modulatory effect on antioxidant capability and microbiota in mice with colitis. Melatonin was demonstrated to improve the oxidative stress resistance of mice with colitis and regulate the intestinal microbial flora, thus improving intestinal health. 10.1155/2018/2607679
Melatonin reduces ulcerative colitis-associated local and systemic damage in mice: investigation on possible mechanisms. Trivedi P P,Jena G B Digestive diseases and sciences BACKGROUND AND AIMS:Ulcerative colitis (UC) is a chronic gastrointestinal disorder. Substantial research reveals that melatonin has beneficial effects in ulcerative colitis both experimentally and clinically. We have previously reported that ulcerative colitis was associated with local and systemic damage in mice. The purpose of this study was to reveal the novel targets of melatonin in its protective mechanism against ulcerative colitis in mice. We also wished to determine whether or not melatonin protected against ulcerative colitis-induced systemic damage in mice. METHODS:Ulcerative colitis was induced in mice by use of 3% (w/v) dextran sulfate sodium for two cycles. One cycle comprised 7 days of DSS-treated water followed by 14 days of normal drinking water. Melatonin was administered at doses of 2, 4, or 8 mg/kg bw/day, po throughout. The effect of melatonin in mice with UC was evaluated by use of biochemical data, histological evaluation, comet and micronucleus assays, immunohistochemistry, and western blot analysis. RESULTS:The results indicated that melatonin treatment ameliorated the severity of ulcerative colitis by modulating a variety of molecular targets, for example nuclear factor kappa B, cyclooxygenase-2, interleukin 17, signal transducer and activator of transcription 3, nuclear erythroid 2-related factor 2, matrix metalloproteinase-9, and connective tissue growth factor. Further, ulcerative colitis increased gut permeability, plasma lipopolysaccharide level, systemic inflammation, and genotoxicity. Melatonin treatment led to mucosal healing and reduced ulcerative colitis-induced elevated gut permeability and reduced the plasma LPS level, systemic inflammation, and genotoxicity. CONCLUSION:Melatonin ameliorated ulcerative colitis-associated local and systemic damage in mice. 10.1007/s10620-013-2831-6
Melatonin expresses powerful anti-inflammatory and antioxidant activities resulting in complete improvement of acetic-acid-induced colitis in rats. Tahan Gulgun,Gramignoli Roberto,Marongiu Fabio,Aktolga Serdal,Cetinkaya Ali,Tahan Veysel,Dorko Kenneth Digestive diseases and sciences INTRODUCTION:Increased free-radical production, decreased antioxidant capacity, and excessive inflammation are well-known features in the pathogenesis of inflammatory bowel disease. Melatonin is a powerful antioxidant and a scavenger of hydroxyl radicals. Melatonin has also been shown to have anti-inflammatory activities in tissues. Our study objective is to investigate the effects of melatonin on tissue inflammatory activities using an ulcerative colitis (UC) model induced by acetic acid (AA) in rats. METHODS:Wistar rats (n = 32) were divided into four groups. AA-induced colitis was performed in two of the groups, while the other two groups were injected with saline intrarectally. One of the AA-induced colitis groups and one of the control groups were administered 100 mg/kg/day melatonin intraperitoneally, and the pair groups were given saline. After 4 days, colonic changes were evaluated biochemically by measuring proinflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6], myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) levels in tissue homogenates and by histopathological examination. RESULTS:AA caused colonic mucosal injury, whereas melatonin suppressed these changes in the AA-induced colitis group (P < 0.001). AA administration resulted in increased TNF-α, IL-1β, IL-6, MPO, and MDA levels, and decreased GSH and SOD levels, whereas melatonin administration reversed these effects (all P < 0.001). CONCLUSIONS:The present study proposes that melatonin has a dual action as an effective anti-inflammatory and an antioxidant, and may be a hopeful therapeutic agent for UC. 10.1007/s10620-010-1364-5
Alterations in melatonin and 5-HT signalling in the colonic mucosa of mice with dextran-sodium sulfate-induced colitis. MacEachern Sarah J,Keenan Catherine M,Papakonstantinou Evangelia,Sharkey Keith A,Patel Bhavik Anil British journal of pharmacology BACKGROUND AND PURPOSE:Inflammatory bowel disease (IBD) is characterized by pain, bleeding, cramping and altered gastrointestinal (GI) function. Changes in mucosal 5-HT (serotonin) signalling occur in animal models of colitis and in humans suffering from IBD. Melatonin is co-released with 5-HT from the mucosa and has a wide variety of actions in the GI tract. Here, we examined how melatonin signalling is affected by colitis and determined how this relates to 5-HT signalling. EXPERIMENTAL APPROACH:Using electroanalytical approaches, we investigated how 5-HT release, reuptake and availability as well as melatonin availability are altered in dextran sodium sulfate (DSS)-induced colitis in mice. Studies were conducted to explore if melatonin treatment during active colitis could reduce the severity of colitis. KEY RESULTS:We observed an increase in 5-HT and a decrease in melatonin availability in DSS-induced colitis. A significant reduction in 5-HT reuptake was observed in DSS-induced colitis animals. A reduction in the content of 5-HT was observed, but no difference in tryptophan levels were observed. A reduction in deoxycholic acid-stimulated 5-HT availability and a significant reduction in mechanically-stimulated 5-HT and melatonin availability were observed in DSS-induced colitis. Orally or rectally administered melatonin once colitis was established did not significantly suppress inflammation. CONCLUSION AND IMPLICATIONS:Our data suggest that DSS-induced colitis results in a reduction in melatonin availability and an increase in 5-HT availability, due to a reduction/loss of tryptophan hydroxylase 1 enzyme, 5-HT content and 5-HT transporters. Mechanosensory release was more susceptible to inflammation when compared with chemosensory release. 10.1111/bph.14163
Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin-1β. Mannino Giuseppe,Caradonna Fabio,Cruciata Ilenia,Lauria Antonino,Perrone Anna,Gentile Carla Journal of pineal research Melatonin is the main secretory product of the pineal gland, and it is involved in the regulation of periodic events. A melatonin production independent of the photoperiod is typical of the gut. However, the local physiological role of melatonin at the intestinal tract is poorly characterized. In this study, we evaluated the anti-inflammatory activities of melatonin in an in vitro model of inflamed intestinal epithelium. To this purpose, we assessed different parameters usually associated with intestinal inflammation using IL-1β-stimulated Caco-2 cells. Differentiated monolayers of Caco-2 cells were preincubated with melatonin (1 nmol/L-50 μmol/L) and then exposed to IL-1β. After each treatment, different inflammatory mediators, DNA-breakage, and global DNA methylation status were assayed. To evaluate the involvement of melatonin membrane receptors, we also exposed differentiated monolayers to melatonin in the presence of luzindole, a MT1 and MT2 antagonist. Our results showed that melatonin, at concentrations similar to those obtained in the lumen gut after ingestion of dietary supplements for the treatment of sleep disorders, was able to attenuate the inflammatory response induced by IL-1β. Anti-inflammatory effects were expressed as both a decrease of the levels of inflammatory mediators, including IL-6, IL-8, COX-2, and NO, and a reduced increase in paracellular permeability. Moreover, the protection was associated with a reduced NF-κB activation and a prevention of DNA demethylation. Conversely, luzindole did not reverse the melatonin inhibition of stimulated-IL-6 release. In conclusion, our findings suggest that melatonin, through a local action, can modulate inflammatory processes at the intestinal level, offering new opportunities for a multimodal management of IBD. 10.1111/jpi.12598
Melatonin alters amino acid metabolism and inflammatory responses in colitis mice. Liu Gang,Jiang Qian,Chen Shuai,Fang Jun,Ren Wenkai,Yin Jie,Yao Kang,Yin Yulong Amino acids Inflammatory bowel disease is a chronic inflammatory dysfunction of the gastrointestinal tract. This study explored the hypothesis that melatonin has beneficial functions in the mouse model of colitis induced by dextran sodium sulfate (DSS), with a specific focus on the expression of intestinal inflammatory cytokines and the serum levels of amino acids. The results revealed that mice with melatonin supplementation had a reduction in weight loss and disease index induced by DSS treatment. Melatonin stifled the expression of colonic IL-17 in mice with DSS-induced colitis. Melatonin also lowered the serum levels of Asp, Ser, Met, and Leu (p < 0.05), but increased those of Glu and Cys (p < 0.05). Thus, melatonin treatment is promising and may function as a potential adjuvant therapy to alleviate the clinical symptoms of patients with inflammatory bowel disease. 10.1007/s00726-017-2489-z
Evaluation of the therapeutic activity of melatonin and resveratrol in Inflammatory Bowel Disease: A longitudinal PET/CT study in an animal model. Seoane-Viaño Iria,Gómez-Lado Noemí,Lázare-Iglesias Héctor,Rey-Bretal David,Lamela-Gómez Iván,Otero-Espinar Francisco J,Blanco-Méndez José,Antúnez-López José Ramón,Pombo-Pasín María,Aguiar Pablo,Ruibal Álvaro,Luzardo-Álvarez Asteria,Fernández-Ferreiro Anxo International journal of pharmaceutics Inflammatory Bowel Disease (IBD) is a group of chronic disorders of the gastrointestinal tract, which two main types are Crohn's disease and ulcerative colitis. Although conventional therapeutic strategies have demonstrated to be effective in the IBD treatment, it is necessary to incorporate novel therapeutic agents that target other mechanisms involved in the pathogenesis of the disease, such as oxidative stress. For this reason, the efficacy in vivo of two antioxidant compounds, melatonin and resveratrol, has been investigated in an animal model of TNBS (2, 4, 6-trinitrobenzenesulfonic acid) induced colitis. PET/CT (Positron emission tomography/Computer Tomography) scans were performed to assess disease activity and evaluate treatment response. SUV (Standardized Uptake Value) values, body weight changes and histological evaluation were used as inflammatory indices to measure the efficacy of both treatments. SUV values increased rapidly after induction of colitis, but after the beginning of the treatment (day 3) a statistically significant decrease was observed on days 7 and 10 in treated animals compared to the non-treated group. This remission of the disease was also confirmed by histological analysis of the colon tissue using the Nancy histological index (p value < 0.05 for differences between non-treated and both groups of treated animals). Moreover, statistical analysis showed a correlation (R = 65.52%) between SUV values and weight changes throughout the treatment. Overall, this study demonstrates the potential of resveratrol, and melatonin in lower extent, as therapeutic agents in the IBD treatment. 10.1016/j.ijpharm.2019.118713
Melatonin-loaded chitosan nanoparticles endows nitric oxide synthase 2 mediated anti-inflammatory activity in inflammatory bowel disease model. Soni Jignesh Mohanbhai,Sardoiwala Mohammed Nadim,Choudhury Subhasree Roy,Sharma Shyam Sunder,Karmakar Surajit Materials science & engineering. C, Materials for biological applications Inflammatory Bowel Disease (IBD) is a complex inflammatory condition arising due to interactions of environmental and genetic factors that lead to dysregulated immune response and inflammation in intestine. Complementary and alternative medicine approaches have been utilized to treat IBD. However, chronic inflammatory diseases are not medically curable. Hence, potent anti-inflammatory therapeutic agents are urgently warranted. Melatonin has emerged as a potent anti-inflammatory and neuroprotective candidate. Although, it's therapeutic efficacy is compromised due to less solubility and rapid clearance. Hence, we have synthesized melatonin loaded chitosan nanoparticle (Mel-CSNPs) to improve drug release profile and evaluate its in-vitro and in-vivo therapeutic efficacy. Mel-CSNPs exhibited better anti-inflammatory response in an in-vitro and in-vivo IBD model. Significant anti-inflammatory activity of Mel-CSNPs is attributed to nitric oxide (NO) reduction, inhibited nuclear translocation of NF-kB p65 and reduced IL-1β and IL-6 expression. In-vivo biodistribution study has shown a good distribution profile. Effective in-vivo therapeutic efficiency of Mel-CSNPs has been confirmed with reduced disease activity index parameters and inhibited neutrophilic infiltration. Histological evaluation has further proved the protective effect of Mel-CSNPs by preventing crypt damage and immune cells infiltration against Dextran Sodium Sulphate induced insults. Immuno-histochemical analysis has confirmed anti-inflammatory action of Mel-CSNPs with reduction of inflammatory markers, Nitric Oxide Synthase-2 (NOS2) and Nitro-tyrosine. Indeed, this study divulges anti-inflammatory activity of Mel-CSNPs by improving the therapeutic potential of melatonin. 10.1016/j.msec.2021.112038
Melatonin Alleviates Neuroinflammation and Metabolic Disorder in DSS-Induced Depression Rats. Lv Wei-Jie,Liu Cui,Yu Lin-Zeng,Zhou Jia-Hao,Li Yue,Xiong Ying,Guo Ao,Chao Li-Min,Qu Qian,Wei Guang-Wei,Tang Xing-Gang,Yin Yu-Long,Guo Shi-Ning Oxidative medicine and cellular longevity 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-1 and TNF-, 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 and significantly increased, while bile salt hydrolase activity-related microbiota, like and , 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. 10.1155/2020/1241894