Effect of antiretroviral therapy on gut microbiota, immune activation, and inflammatory markers in newly diagnosed HIV patients.

INTRODUCTION

People living with HIV (PLWH) exhibit gut dysbiosis and chronic immune activation. The early dynamics of the gut-immune axis during the transition from diagnosis to viral suppression remain incompletely understood.

METHODS

We characterized fecal microbiota (16S rRNA), bacterial translocation (16S rDNA) and gut barrier integrity (serum intestinal fatty acid-binding protein, I-FABP, level) in newly diagnosed PLWH at baseline (t0) and after six months of suppressive ART (t6), compared to uninfected controls. Systemic inflammation (serum concentrations of interleukins 6 and 10, soluble CD163), and peripheral blood T-cell activation were also analyzed.

RESULTS

Alpha diversity was similar across groups (p>0.05); beta diversity differed significantly between PLWH at t0 and controls (p=0.002). Linear Discriminant Analysis Effect Size (LEfSe) analysis identified an enrichment of short chain fatty acids (SCFA)-producing genera (Alloprevotella, Mitsuokella, Succinivibrio, Megasphaera) in PLWH at t0. PLWH at t0 showed elevated bacterial translocation [16S rDNA, 4281 (4018-4485) vs 2162 (2023-2286) copies/mL, p<0.001], gut barrier damage [I-FABP, 950 (800-1168) vs 767 (574-902) ng/mL, p=0.012], inflammation [IL-6, 4.8 (3.1-8.8) vs 0.8 (0.3-1.3) pg/mL, p<0.001; sCD163, 1173 (872-1417) vs 561 (425-662) ng/mL, p<0.001], and T-cell activation [CD4+CD38+HLA-DR+ (percentage of CD4+ T lymphocytes), 9.7 (2.8-18.5) vs 1.3 (0.3-2.2), p=0.007; CD8+CD38+HLA-DR+ (percentage of CD8+T lymphocytes), 19.0 (12.0-31.1) vs 1.7 (0.6-5.7), p=0.005], compared with controls. Treated PLWH (t6) showed similar alpha and beta diversities of fecal microbiota compared to untreated PLWH (p>0.05 in each case). LEfSe analysis identified an enrichment of Campylobacter and Atopobium at t6. ART mitigates systemic inflammation [t6 vs t0, IL-6, 3.3 (1.7-4.0) vs 4.8 (3.1-8.8) pg/mL, p=0.022; sCD163, 795 (549-915) vs 1173 (872-1417) ng/mL, p<0.001], and T-cell activation [t6 vs t0, CD4+CD38+HLA-DR+ (percentage of CD4+ T lymphocytes), 2.7 (1.7-6.3) vs 9.7 (2.8-18.5), p=0.047; CD8+CD38+HLA-DR+ (percentage of CD8+T lymphocytes), 6.5 (3.7-15.5) vs 19.0 (12.0-31.1), p=0.086].

CONCLUSIONS

Untreated PLWH show a dysbiotic signature, characterized by enrichment of SCFA-producers. Compared to controls, the fecal microbiota of PLWH after 6 months of ART (t6) continued to show differences characterized by a predominance of Alloprevotella and Succinivibrio, among others, and continued elevations in intestinal injury, bacterial translocation, and inflammatory/immune activation markers, underscoring the incomplete normalization of gut-immune homeostasis.