Associações entre obesidade e microbiota intestinal na tuberculose experimental

Abstract

Obesity is a current health problem. According to WHO, in 2016, 39% of adults aged 18 years old or older were overweight and 13% were diagnosed with obesity. In Brazil, this scenario is even more worrisome, while data indicate a percentage of overweight adults of 54% and obese individuals of 18.9%, by the Ministry of Health (2019). It has already been shown that obesity or overweight are protective factors in the evolution of infectious diseases such as Tuberculosis (TB). In addition, in individuals with high body mass index (BMI) they have higher systemic levels of proinflammatory cytokines and a decrease in anti-inflammatory cytokines. The microbiota composition of eutrophic and obese individuals are different and may influence the development of obesity, as well as having significant role in the modulation of the host immune system. Thus, this study aimed to evaluate the associations between obesity and the gut microbiota in experimental TB. For this, male mice of the C57BL/6 lineage were submitted to a hyperlipidic or standard diet and infected or not with Mycobacterium bovis BCG at 24, 48, 72 and 96 hours. Our data demonstrated that the hyperlipidic diet was able to induce obesity after 12 weeks. Interestingly, there was a significant weight loss in obese animals after 96h of infection by M. bovis BCG. There was an increase in the formation of lipid bodies in face of infection in both groups studied, but obesity seems to positively modulate this biogenesis in 72 and 96h. However, after 96h of infection, in both groups, there was a significant decrease in the formation of these organelles. Our data also showed increased secretion of proinflammatory cytokines (TNF-α and KC) in face of infection and a decrease in IL-10 levels in obese animals after 48h. Histological analyzes of the gut indicated an increased area of inflammatory infiltrates in the gut of obese animals in 48h. However, interestingly, in both groups, eutrophic and obese, there was a significant reduction in the area of inflammatory infiltrates after 96h of infection. Through the structural analysis of the gut microbiota of the mice, it was possible to demonstrate that there are differences between the eutrophic and obese groups. The gut microbiota (GM) structure of the eutrophic animals underwent changes rapidly and continued to vary at 24, 48 and 72h after infection. The change in the gut microbiota structure of obese animals was slow, with minor changes at 24 and 48 hours, and significant changes in the time of 72h, which approached the microbial profile of the eutrophic animals after 24h of infection. The hyperlipidic diet was able to induce obesity in the animal model but BCG infection induced loss of body weight after 96h of infection (98.3% similarity). In addition, obese animals after 96h of infection undergo drastic changes in the composition of the GM showing 55.1% similarity with the other groups. Changes in the composition of the gut microbiota and their associations to infectious diseases are still poorly understood and further investigation into their interactions with the immune system are necessary.