Portugal 2022 Portugal Grant Winner
Microbiota e ABCD (Doença Crónica Baseada na Adiposidade)
Pr. Teresa Gonçalves, Universidade de Coimbra (UC)
Mycobiota METabolism Adenosine for Obesity – MMETA4Obesity
Metabolic diseases, including obesity are multifactorial, resulting both from genetics, and from individual environmental habits, such as diet or physical exercise. In the last decades it has become clear the importance of microbiota, particularly the gut microbiota/microbiome. However, most of the studies are focused on the bacterial components of the microbiota, and the role of the fungal elements of these microbial populations, the mycobiota, has been neglected. Nevertheless, recent data point to the importance of these commensal fungi in metabolic diseases, such as obesity, diabetes, or chronic inflammatory diseases. Importantly, another factor playing a role in metabolic diseases is the purinergic system, in particular adenosine and adenosine receptors. In fact, these receptors control cellular mechanisms that ultimately counteract obesity. On the other hand, we showed that the adenosine A2A receptor (A2AR) is able to modulate Candida albicans virulence, one of the main gut mycobiota elements, decreasing gut damage. With these premises in mind, we hypothesize that in people with obesity, mycobiota homeostasis is under the regulation of adenosine receptors; and that a balance between adenosine receptor expression and mycobiota will relate with metabolic health.
To tackle this innovative perspective on obesity, we will recruit subjects with obesity, that will undergo bariatric surgery at CHUC. Fasting blood samples, adipose and gut tissue, as well as feces will be collected. To test our hypothesis we will (1) characterize the gut mycobiota, and relate that with (2) adenosine receptors expression and gene polymorphisms in adipose and gut tissues from subjects with obesity at different stages and insulin sensitivity (insulin sensitive versus insulin resistant); and (3) assess overall inflammatory markers, and relate that with the mycobiota and adenosine receptors expression.
This proposal constitutes an opportunity to identify novel targets to reverse or counteract obesity.