The Microbiota-Dependent Worsening Effects of Melatonin on Gut Inflammation

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da Silva, Jefferson Luiz ; Barbosa, Lia Vezenfard ; Pinzan, Camila Figueiredo ; Nardini, Viviani ; Brigo, Irislene Simoes ; Sebastiao, Cassia Aparecida ; Elias-Oliveira, Jefferson ; Brazao, Vania ; do Prado Junior, Jose Clovis ; Carlos, Daniela ; Cardoso, Cristina Ribeiro de Barros

• Document type: Journal article
• Source: MICROORGANISMS; v. 11, n. 2, p. 16-pg., 2023-02-01.

Abstract

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. (AU)

• FAPESP's process: 17/08651-1 - Immunomodulatory effects of dehidroepiandrosterone (DHEA) in the immune response of Crohn's disease patients refractory to anti-TNF treatment
• Grantee: Cristina Ribeiro de Barros Cardoso
• Support Opportunities: Regular Research Grants