Gut microbiome taxonomic and predicted functional profiles in Tunisian individuals with hypercholesterolemia: a pilot study.

Hypercholesterolemia is a major cardiovascular risk factor that has been increasingly associated with alterations of the gut microbiota. However, microbial signatures remain inconsistent across populations, and data from North African populations are currently lacking. This study aimed to characterize gut microbiota alterations associated with hypercholesterolemia in a Tunisian cohort while integrating taxonomic and functional analyses. Fecal samples from 18 hypercholesterolemic patients and 17 normocholesterolemic controls were analyzed by 16S rRNA gene (V3-V4) sequencing. Taxonomic composition was assessed using multiple complementary differential abundance methods, while microbial functional potential was inferred using Tax4Fun2, PICRUSt2, and FAPROTAX. Global microbial diversity and community structure were largely preserved between groups. However, hypercholesterolemic patients exhibited increased inter-individual variability and subtle but significant shifts at finer taxonomic resolution. While the overall predicted functional potential of the microbiota remained relatively stable, consistent trends across complementary analytical approaches indicated a relative depletion of pathways related to carbohydrate fermentation and short-chain fatty acid-associated metabolism in hypercholesterolemic individuals. In contrast, control subjects displayed a stronger functional signature associated with metabolic homeostasis. Despite taxonomic heterogeneity, predicted functional redundancy appeared to be partially maintained across groups. Hypercholesterolemia was associated with a selective and heterogeneous remodeling of the gut microbiota rather than a uniform dysbiosis. Despite preserved global microbial diversity, disease-associated changes were observed at finer taxonomic and predicted functional levels. As the first study investigating gut microbiota-hypercholesterolemia associations in a Tunisian population, these findings provide baseline data from an understudied North African cohort and identify candidate microbial signatures that warrant validation in larger multi-center studies.