Abstract
The global prevalence of Metabolic dysfunction-associated steatotic liver disease (MASLD) among persons with HIV (PWHIV) is estimated at 34%. This study examined the influence of gut microbial and metabolic alterations in PWHIV with MASLD. We conducted 16S rRNA sequencing on 60 fecal samples (24 from HIV group and 36 from HIV-MASLD group) to assess microbial composition, and employed LC/MS-based metabolomics on both fecal and plasma samples to identify variations in metabolites. An exploratory analysis was performed to compare plasma cytokines and oxidative stress markers between the two groups. Sequencing in the HIV-MASLD group showed lower Faecalibacterium and Anaerobutyricum, and higher Klebsiella, Escherichia, and Enterococcus. Metabolomic analysis revealed a reduction in anti-inflammatory metabolites (Dodecanedioic acid, 5-Phenylvaleric acid, Kynurenic acid) and antioxidant metabolites, coupled with an increase in the pro-inflammatory metabolite Gamma-Glutamyl-L-Putrescine in the HIV-MASLD group. And plasma analysis indicated a decline in 20-carboxy arachidonic acid. Additionally, Faecalibacterium and Anaerobutyricum correlated positively with anti-inflammatory metabolites, while Klebsiella, Enterobacter, and Citrobacter correlated negatively. Furthermore, Faecalibacterium and Anaerobutyricum also showed a moderate negative correlation with MDA levels. A random forest model using plasma metabolites showed the optimal discriminative ability for HIV-MASLD (AUC = 0.819 ± 0.0059). Differences in gut microbiota and metabolites in PWHIV may affect MASLD progression by influencing inflammation and oxidative stress. Modulating gut microbiota, such as adding Faecalibacterium and Anaerobutyricum, could be a treatment strategy for HIV-MASLD. Plasma metabolites have potential as noninvasive markers.