Abstract
Damage to the intestinal mucosal barrier and dysbiosis of the gut microbiota are critical factors in HIV progression, reciprocally influencing each other. Besides bacteria, the fungal microbiota, a significant component of the gut, plays a pivotal role in this dysregulation. This study aims to investigate changes in the gut mucosal barrier and mycobiota during the initial stages of HIV infection, focusing on the involvement of intestinal fungi and their secretions in mucosal damage. Peripheral blood, intestinal mucosa, and fecal samples were collected from 13 asymptomatic HIV-infected individuals at the non-AIDS stage and 13 healthy controls. Assessments included colonoscopy, immune function analysis, and measurement of mucosal damage markers (LPS, I-FABP, and D-LA) and inflammatory cytokines (IL-6 and IL-18). Additionally, Claudin-1 levels in mucosal samples and fungal profiles in fecal samples were evaluated. The study found that colonic abnormalities were significantly more prevalent in the HIV group compared to healthy controls (p < 0.001) and Claudin-1 levels were notably lower in the HIV group (p < 0.001). Candida albicans (p=0.0084), its secretion SAP1 (p=0.023), and the levels of IL-18 (p=0.0016) and IL-6 (p < 0.001) were all significantly higher in the HIV group. CD4+ T-cell counts were positively correlated with Claudin-1 expression (p=0.034, r = 0.417). Candida albicans showed negative correlations with several virulence factors, while other fungi exhibited varied correlations. Additionally, Claudin-1 levels were significantly negatively correlated with Candida albicans (p=0.013, r = -0.668), SAP1 (p=0.027, r = -0.609), IL-18 (p < 0.001, r = -0.922), and IL-6 (p < 0.001, r = -0.920). Overall, these findings suggest that asymptomatic HIV-infected individuals have already exhibited intestinal mucosal damage in the early stage and highlight the critical role of Candida albicans and its secretions in early-stage intestinal mucosal barrier damage.