Fungal β-glucan instructed miR-32-5p modulates Dectin-1 signaling mediated inflammation, reactive oxygen species and apoptosis through polarization of “M2a-like” macrophage in <i>Candida</i> colitis

Ulcerative colitis (UC) is a chronic and easy-to-relapse intestinal disease characterized by colon inflammation and microbial dysbiosis. <i>Candida albicans</i> is the most common fungal resident in the human gut. Overgrowth of <i>C. albicans</i> has been linked to the aggravation of UC. Previously, we demonstrated that miR-32-5p was the most differentially expressed microRNA in DSS-induced colitis model supplemented with <i>C. albicans</i> and might be a potential target in the treatment of <i>Candida</i> colitis. However, the underlying pathogenic and therapeutic mechanisms remain unclear. Here, we firstly used the ITS technique to analyse intestinal mycobiota. The miR-32-5p adenovirus in company with extracted <i>Candida</i> cell wall β-glucan were then employed to monitor the impacts of miR-32-5p and fungal β-glucan on the severity of <i>Candida</i> colitis. Subsequently, gene silencing together with inhibitors of reactive oxygen species (ROS) and apoptosis was used to survey the modulation of miR-32-5p on macrophage polarization. According to these results, <i>C. albicans</i> became the dominant intestinal fungal species in <i>Candida</i> colitis model. <i>Candida</i> β-glucan could instruct miR-32-5p expression to affect the severity of <i>Candida</i> colitis in a concentration-dependent manner. Interestingly, high fungal β-glucan with pro-inflammatory effects hindered further increases in gut inflammation. Further analysis showed that overexpression of miR-32-5p could effectively inhibit inflammation and apoptosis and enhance phagocytosis and ROS production through Dectin-1 signalling in macrophages. A panel of representative gene expressions verified the polarization of the M2-like phenotype induced by miR-32-5p. Mechanistically, our results reveal the therapeutic potential of miR-32-5p in the amelioration of <i>Candida</i> colitis.