O intestino como sítio de estudo da interação entre esquistossomose mansoni, síndrome metabólica e microbiota intestinal

Abstract

Schistosomiasis is a neglected disease that affects millions of people worldwide. It is known that concomitant schistosomiasis mansoni and metabolic syndrome (MS) intensify lesions in liver tissue, but the interaction of these two diseases in the gut and the role of the microbiota together remains undefined. Therefore, using a model of diet-induced obesity, we sought to address this gap. Male C57BL/6 mice fed a high-fat diet (60% lipids) or a standard diet (10% lipids) for 13 weeks were infected with 100 Schistosoma mansoni cercariae (strain BH). The mice were then allocated into four groups: CDP (control fed a standard diet), CDH (control fed a high-fat diet), IDP (infected fed a standard diet) and IDH (infected fed a high-fat diet). One week before euthanasia, the feces of each animal was collected for co-culture and microbiota analysis by MALDI-TOF. The animals then underwent an oral glucose tolerance test. Euthanasia took place 21 weeks after the start of the diet and at 9 weeks of infection. Blood samples were collected for biochemical lipid analysis. We assessed the activity of the cytokines of the resident macrophages of the peritoneum (IL-6, IL-10, MCP-1, IFN-γ and TNF). Fat deposits were removed to calculate the adiposity indices. Sections of the intestine were used for KOH digestion and crushing, and the adult helminths recovered were fixed and stained for morphometric analysis. Histological sections of the jejunum were removed and subjected to routine histological processing, morphometric analyses of the jejunum segment were performed, inflammation points, goblet cell frequency and fluorescence in situ hybridization (FISH). Our results showed that IDH had a reduced lipid profile and better oral glucose tolerance, as well as a reduced body mass. IDP had slightly more worm couples than IDH, and consequently eliminated more eggs, although there was no statistical difference between the groups. The male helminths fed the high-fat diet had larger testicular lobes and the females had larger ovarian areas and perimeters than the control. Infection was a greater determinant of the expression of cytokines in resident macrophages than MS. Firmicutes and Proteobacteria were the phyla identified. The Klebsiella variicola species was identified only in IDH. FISH revealed a distribution of bacteria in the mucosal layers, especially in the Lieberkühn crypts, in the submucosa and muscle, suggesting a possible translocation of bacteria in IDH, which also showed villous hyperplasia, Paneth cell hypertrophy, loss of epithelial mucosa, submucosal alterations and external muscle integrity. Schistosomiasis also induces profound effects on intestinal homeostasis during egg transmigration through the gastrointestinal wall, resulting in inflamed and permeable intestinal tissue. Taken together, our data suggest that concomitant MS and acute schistosomiasis have a significant impact on the architecture of the jejunum in C57BL/6 mice.