The Microbiota-Dependent Worsening Effects of Melatonin on Gut Inflammation.

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.

Endocrine and immune system interactions during pregnancy.

Pregnancy is known to induce a transient depression of maternal cell-mediated immunity, to prevent rejection of the fetus, while at the same time it keeps adequate maternal host defense mechanisms to fight infection. Presently, the aim of this paper was to investigate a possible endocrine and immunologic alteration observed during a successful pregnancy. This study consistently showed that plasma corticosterone levels were significantly higher (P<0.0001) in pregnant Wistar rats than in virgin female. An increased number of peritoneal macrophages was also detected in pregnant females when compared to non-pregnant ones. Macrophages play an important role in the production of bioactive proteins and lipids such as nitric oxide. Then, in support of the latter, the present study showed increased levels of endogenous NO in pregnant rats when compared to non-pregnant ones, thereby mediating the vasodilatation process of normal gestation. Furthermore, our FACS analysis clearly indicated the correlation between reduced CD161 expression on NK cells (P<0.0001) in pregnant rats when compared to virgin females. It was found that pregnancy appears to be associated with depressed cell immunity, as evidenced by a significant inhibition of lymphocyte proliferation. Understanding the immunological paradox of maternal tolerance, as well as the hormonal modulation of the immune environment during pregnancy is essential for future studies to investigate the potential for these processes to be modulated by diet or effective therapeutics during pregnancy.