Hypercholesterolemia was associated with a selective and heterogeneous remodeling of the gut microbiota rather than a uniform dysbiosis, with preserved global microbial diversity but disease-associated changes observed at finer taxonomic and predicted functional levels in a Tunisian cohort.
Key Findings
Results
Global microbial diversity and community structure were largely preserved between hypercholesterolemic patients and normocholesterolemic controls.
Fecal samples from 18 hypercholesterolemic patients and 17 normocholesterolemic controls were analyzed by 16S rRNA gene (V3-V4) sequencing.
Alpha diversity metrics did not show significant differences between groups.
Beta diversity (community structure) was also largely preserved between groups.
This finding contrasts with some prior studies reporting marked dysbiosis in hypercholesterolemia.
Results
Hypercholesterolemic patients exhibited increased inter-individual variability in gut microbiota composition compared to controls.
Greater inter-individual variability was observed in the hypercholesterolemic group despite preserved overall community structure.
This heterogeneity suggests that hypercholesterolemia-associated microbiota changes are selective rather than uniform.
The authors described this pattern as 'selective and heterogeneous remodeling of the gut microbiota rather than a uniform dysbiosis.'
Results
Significant taxonomic shifts were detected at finer taxonomic resolution in hypercholesterolemic individuals despite no major phylum-level differences.
Multiple complementary differential abundance methods were used to assess taxonomic composition.
Subtle but significant shifts were identified at finer taxonomic levels (below phylum level).
Taxonomic heterogeneity was noted across the hypercholesterolemic group, indicating no single universal microbial signature.
The study identified candidate microbial signatures associated with hypercholesterolemia in this Tunisian population.
Results
Hypercholesterolemic individuals showed a relative depletion of predicted pathways related to carbohydrate fermentation and short-chain fatty acid (SCFA)-associated metabolism.
Functional potential was inferred using three complementary tools: Tax4Fun2, PICRUSt2, and FAPROTAX.
Consistent trends across all three analytical approaches indicated reduced carbohydrate fermentation and SCFA-associated metabolic pathways in hypercholesterolemic patients.
The overall predicted functional potential of the microbiota remained relatively stable between groups.
Predicted functional redundancy appeared to be partially maintained across groups despite taxonomic differences.
Results
Control subjects displayed a stronger predicted functional signature associated with metabolic homeostasis compared to hypercholesterolemic patients.
Normocholesterolemic controls showed enrichment in functional pathways linked to metabolic homeostasis.
This functional difference was identified consistently across Tax4Fun2, PICRUSt2, and FAPROTAX analyses.
Despite the functional differences, overall predicted functional potential remained relatively stable, suggesting partial functional redundancy.
Background
This is the first study to investigate gut microbiota-hypercholesterolemia associations in a Tunisian (North African) population.
The study is described as a pilot study with a total of 35 participants (18 hypercholesterolemic, 17 controls).
The authors note that 'data from North African populations are currently lacking' and that microbial signatures 'remain inconsistent across populations.'
The findings are intended to 'provide baseline data from an understudied North African cohort.'
The authors call for validation in larger multi-center studies.
What This Means
This research suggests that people with high cholesterol (hypercholesterolemia) in Tunisia have subtle but meaningful differences in their gut bacteria compared to people with normal cholesterol levels. Interestingly, the overall diversity and general makeup of gut bacterial communities looked similar between the two groups — meaning high cholesterol does not appear to cause a wholesale collapse of the gut microbiome. Instead, the differences were found at a more detailed level, with specific types of bacteria being more or less abundant in people with high cholesterol, and with much more variation from person to person in the high-cholesterol group.
When the researchers looked at what the gut bacteria might be doing (their predicted functions), they found that bacteria from people with high cholesterol appeared less active in producing short-chain fatty acids — beneficial compounds made when gut bacteria break down dietary fiber. These compounds are known to help regulate metabolism and support gut health. Control participants showed stronger predicted activity in pathways linked to maintaining metabolic balance. These functional differences were consistently identified across three different analytical tools, lending confidence to the findings.
This matters because it is the first study of its kind conducted in a North African population, and prior research has shown that gut microbiome patterns can differ significantly between populations. This research suggests that high cholesterol is linked to a subtle, patchy reshaping of gut bacteria rather than a dramatic disruption, and that these changes may affect how the gut microbiome supports metabolic health. The authors emphasize that these are preliminary findings from a small pilot study and that larger studies are needed to confirm and expand upon these results.
Ncir W, Frikha H, Derbel R, Belgith I, Ammous-Boukhris N, Mokdad-Gargouri R, et al.. (2026). Gut microbiome taxonomic and predicted functional profiles in Tunisian individuals with hypercholesterolemia: a pilot study.. World journal of microbiology & biotechnology. https://doi.org/10.1007/s11274-026-05228-x