Enzyme-activated biosensor for visually sensing intestinal fungi aryl sulfatase and its applications in fluorescence-guided therapy of inflammatory bowel diseases

Aryl sulfatase (ARS) as a widely expressed enzyme in intestinal flora is mainly responsible for the hydrolysis of sulfation metabolites of endogenous and exogenous substances in gut and mediates the reabsorption of functional molecules especially for the estrogen. In this work, an enzymatic-activated near-infrared (NIR) fluorescent probe DSACS, was developed for sensing ARS in complicated biological samples that exhibited high sensitivity and selectivity toward ARS and firstly realized real-time imaging endogenous ARS in intestinal fungi. Moreover, a visual high-throughput evaluation method for ARS activity was established using DSACS, and five yeast strains (PB005A, PK2101B, PX1910, PA3318 and S30-09) possessing high ARS activity were screened out from 48 kinds of human intestinal yeast strains. These five strains could efficiently catalyze the hydrolysis of estrogen sulfates to produce the estrogen, finally, intestinal colonization of PB005A exhibited excellent tolerance and resistances toward DSS-induced inflammatory bowel diseases (IBD) through promoting the recovery reabsorption of estradiol further activated ER dependent anti-inflammatory pathways. Our findings provided a promising tool for exploring the physiological and pathological functions of intestinal fungi ARS in enterohepatic circulation of estrogen, and revealing their potential powerful function in IBD.