Dysbiosis and disturbances in gut homeostasis may result in dysregulated responses, which are common in inflammatory bowel diseases (IBD). These conditions may be refractory to the usual treatments and novel therapies are still necessary to reach a more successful regulation of intestinal immunity. The hormone melatonin (MLT) has been raised as a therapeutic alternative because of its known interactions with immune responses and gut microbiota. Hence, we evaluated the effects of MLT in experimental colitis that evolves with intestinal dysbiosis, inflammation and bacterial translocation. C57BL/6 mice were exposed to dextran sulfate sodium and treated with MLT. In acute colitis, the hormone led to increased clinical, systemic and intestinal inflammatory parameters. During remission, continued MLT administration delayed recovery, increased TNF, memory effector lymphocytes and diminished spleen regulatory cells. MLT treatment reduced Bacteroidetes and augmented Actinobacteria and Verrucomicrobia phyla in mice feces. Microbiota depletion resulted in a remarkable reversion of the colitis phenotype after MLT administration, including a counter-regulatory immune response, reduction in TNF and colon macrophages. There was a decrease in Actinobacteria, Firmicutes and, most strikingly, Verrucomicrobia phylum in recovering mice. Finally, these results pointed to a gut-microbiota-dependent effect of MLT in the potentiation of intestinal inflammation.
µL-Microlitro. µm-Micrômetro. ANOVA-Análise de variância simples. APCs-Células Apresentadoras de Antígenos, do inglês "antigen presenting cells". BrdU-Bromodeoxiuridina BSA-Fração V da albumina sérica bovina, do inglês "bovine serum albumin".
The inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis are immunological dysfunctions of the gastrointestinal tract that develop because of multifactorial processes, including genetic predisposition, gut dysbiosis, and excessive inflammation in susceptible subjects. These pathologies affect millions of people worldwide, with substantial impact on healthcare systems and patients' quality of life. Considering the chronic inflammation that underlies the IBD presentation, the main treatment options are related to the control of patients' inflammatory response, through immunosuppressor and modulatory therapies. Therefore, in this chapter we reviewed the main mechanisms associated with the treatments that are aimed at suppressing mucosal immunity and the effects of corticosteroid therapies in Crohn's disease and ulcerative colitis.
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