Microbial Signatures in Metabolic Syndrome Individuals: A Distinct Intestinal Microbiota Composition Profile Prevails in People Living with HIV Compared to HIV-Negative Individuals

Metabolic syndrome (MetS) is highly prevalent in people living with HIV (PLHIV), but whether their intestinal microbiota differs from that of HIV negative individuals with MetS remains unclear. We conducted a cross-sectional study including 30 virologically suppressed PLHIV with MetS and 30 HIV-negative individuals with MetS. Fecal microbiota composition was assessed by 16S rRNA gene sequencing, and predicted functional profiles were inferred using PICRUSt2 and MetaCyc. PLHIV with MetS exhibited markedly reduced alpha diversity and a clearly distinct beta diversity profile compared with HIV negative MetS, indicating a remodeled community structure. Differential abundance analysis showed enrichment in PLHIV + MetS of Prevotella, Selenomonas, Odoribacter, Christensenellaceae R-7 group, and uncultured Lachnospiraceae, whereas Subdoligranulum and the Ruminococcus gauvreauii group were relatively more abundant in HIV negative MetS. Functional predictions revealed higher representation in PLHIV + MetS of Gram-negative cell envelope and lipopolysaccharide-related pathways, amino acid degradation, and ppGpp biosynthesis, while HIV negative MetS showed comparatively greater saccharolytic potential. Carbohydrate related pathways correlated positively with adiposity and blood pressure, and Prevotella correlated positively with BMI only in PLHIV + MetS. These findings support MetS in chronic treated HIV as a distinct dysbiotic and metabolically adverse intestinal phenotype and highlight the intestinal microbiota as a potential target for microbiome-oriented interventions in this population.