Efeitos de um nutracêutico (Limosilactobacillus fermentum (139, 263, 296) e casca de jabuticaba) na microbiota intestinal e tratamento do diabetes mellitus gestacional em ratas Wistar e sua atividade na saúde cardiometabólica da prole

Abstract

Changes in the gut microbiota can influence the development of gestational diabetes mellitus (GDM), which is associated with systemic disorders such as increased glucose intolerance, insulin resistance, hormonal imbalances and increased inflammation. The combined use of probiotics and prebiotics can promote improvements in parameters associated with GDM. With this in mind, the main objective of this study was to evaluate the effects of treatment with a nutraceutical composed of lyophilized strains of Limosilactobacillus fermentum(139, 263 and 296) and jaboticaba peel on the gut microbiota and the treatment of GDM, and its activity on the cardiometabolic health of offspring. This is a preclinical study in which 36 Wistar rats were randomly divided into three experimental groups: CTL(control, n = 12), GDM(gestational diabetes + vehicle, n = 12) and GDM+Nut(gestational diabetes + nutraceutical, n = 12). Rats in the GDM and GDM+Nut groups were fed a high-fat diet in combination with a 20% sucrose solution, and a single dose of streptozotocin (25 mg/kg) was administered on day 0 of gestation. Rats in the GDM and GDM+Nut groups were treated daily by oral gavage with phosphate-buffered saline vehicle (1ml) and nutraceuticals (2g/kg), respectively, until the end of gestation. Food consumption, gestational weight gain, oral glucose tolerance test and maternal biochemical tests were assessed. Offspring were randomly assigned to 8 females and 8 males per group: OCTL (CTL group offspring), OGDM (GDM group offspring) and OGDM+Nut (GDM+Nut group offspring). The offspring were measured and weighed from the beginning to the end of the experiment, and were also tested for glucose intolerance and insulin resistance, blood pressure, heart rate and autonomic function. The results of this study showed that the GDM group had glucose intolerance. However, administration of the nutraceutical formulation was able to reduce glucose intolerance and serum levels of inflammatory cytokines such as TNF-α and IL-6. Administration of the nutraceutical formulation increased the Firmicutes/Bacteroidota ratio and beta diversity, but did not alter alpha diversity indices compared to the GDM group. An increase in bacteria producing short chain fatty acids, especially butyrate, was observed, such as Mediterraneibacter, Anaerostipes and Flavonifractor. Evaluating the effects of maternal administration of the nutraceutical formulation on the offspring, there was an increase in birth weight and length parameters. During weaning and puberty, the female offspring of the GDM+Nut group showed an increase in length and weight compared to the offspring of the other groups. The offspring of rats treated with the nutraceutical formulation showed no improvement in glucose tolerance compared with the offspring of GDM rats. Meanwhile, the offspring of gestational diabetes rats showed an increased risk of cardiovascular disease, with increases in systolic, diastolic and mean arterial pressure, as well as autonomic nervous system dysfunction. However, maternal consumption of the nutraceutical during pregnancy significantly reduced these parameters in the offspring and consequently the risk of developing cardiovascular disease in adulthood.