Comorbidade obesidade-tuberculose: influência no sistema imune e na microbiota intestinal

Abstract

Tuberculosis (TB) is the second leading cause of death from infectious diseases worldwide. According to WHO, by 2014, 39% of world's adult population were overweight and 13% were diagnosed with obesity. Studies have shown that obesity or overweight are related to a decreased risk of developing active TB. In addition, people with a high body mass index have been shown to have elevated systemic proinflammatory cytokine levels and decreased levels of anti-inflammatory cytokines. In addition, both obese humans and mice have a microbial composition that is significantly different from eutrophic groups, considered lean, and may be co-responsible for the emergence of obesity. It is now recognized that the intestinal microbiota maintains a complex and reciprocal interaction with the host immune system. Thus, the objective of this study is to evaluate whether obesity promotes physiological changes in mice infected with BCG, focusing on changes in the intestinal microbiota. C57/BL6 mice fed a standard or hyperlipidic diets were used. Mice were infected or not with M. bovis BCG. After 24, 48 or 72h of infection the mice were euthanized in a carbon dioxide chamber (CO2). Fecal samples were collected daily after infection to identify the composition of the intestinal microbial structure. Pleural lavage was performed and pleural leukocytes were mounted on laminae for analysis of lipid bodies (LB) and the supernatant of this lavage was used for cytokine analysis. In addition, the final portion of the intestine was collected for histological analysis. Retroperitoneal and perigonadal fats were removed for weighing. After 16 weeks, the mice fed a hyperlipid diet were obese. We evaluated that the infection induced the biogenesis of lipidic corpuscles in both eutrophic and obese mice. Moreover, obese mice 72h after infection showed a significant increase in lipid bodies as compared to eutrophic mice. In addition, we observed that the infection induced an increase in the synthesis of KC and TNF-α, and obesity failed to change these levels. Regarding IL-10, we observed a reduction in the synthesis levels in obese mice with 72h of infection when compared to eutrophic mice. Moreover, we demonstrated that the obese mice presented a structural profile of the intestinal microbiota different when compared to the eutrophic In the eutrophic mice, M. bovis BCG infection rapidly modified the structure of the microbial community, showing variations in 24, 48 and 72 hours. We observed that obesity delayed the change in the structure of the intestinal microbiota. In addition, minor changes were observed at 24 and 48 hours post infection, however, visible changes occurred after 72h of infection. In addition, an increase in the area of inflammatory bowel infiltrates in

response to infection was observed in the obese group. Thus, we suggest that obesity influences the course of infection by modulating biogenesis of lipid bodies, cytokine synthesis, intestinal inflammatory infiltrates and structural composition of intestinal microbiota. Moreover, the possible protective effect of obesity on the development of tuberculosis may occur in other ways, by resistance to the structural change of the intestinal microbiota and by the consequent stimulation of the immune system.