FK506 binding protein 5 deficiency regulates gut microbiome against diet-induced obesity in mice

The FK506-binding protein 51 (FKBP51), encoded by the FKBP5 gene, acts as a cochaperone for the heat shock protein 90 (Hsp90) and is best known for the negative regulation of glucocorticoid and progesterone receptors. Recently, it has been reported that co-chaperone FKBP5 is a stress-responsive protein-regulating stress reactivity, and its genetic variants are associated with T2D related traits and other stress-related disorders. Furthermore, it has been shown that systemic FKBP5 deficiency could significantly decrease blood glucose levels, improve insulin sensitivity and increase the resistance to diet-induced obesity (DIO). Besides host genetic and environmental factors, the gut microbiota has been recognized as a major regulator in the development of obesity. However, whether or not FKBP5- deficiency-mediated effects on obesity function via the gut microbiota remains unclear. In this study, we assessed the potential obesity protection role of the gut microbiota in FKBP5-knockout (FKBP-KO) mice and further profiled the gut microbiome profile modulated by FKBP5 deficiency.