Distinct gut microbial species, but not phylum-to-genus composition, associate with insulin resistance: a unique perspective from the Kazakh population.

Objectives: Links between gut microbiota and insulin resistance (IR) vary across populations. We profiled the fecal microbiota of Kazakh adults to test whether community composition associates with IR at broad (phylum → genus) and species levels. Methods: In a cross-sectional case control study ( Results: High-level composition did not differ between IR and controls (phylum, class, family, genus; all Conclusion: In this Kazakh cohort, no broad compositional signal emerged, but species-specific associations were strong and bidirectional. Findings highlight population-specificity and identify candidate species associated with IR that may serve as hypothesis-generating targets for future validation. Any attempt to modulate these taxa for insulin resistance is unproven and requires function-resolved, diet-measured longitudinal studies and randomized trials before clinical application. The IR:control imbalance (183:17) increases uncertainty for low-prevalence taxa; species-level findings are hypothesis-generating and require validation in a more balanced design. Because 16S rRNA profiling does not measure gene functions or metabolites, these species-IR associations are hypothesis-generating and warrant validation using shotgun metagenomics and metabolomics.