Functional gut microbiome signatures underlying interindividual variability in metabolic responses to red raspberry consumption.

Red raspberries have been shown to exert beneficial effects on immunometabolic health in numerous studies; however, these effects are subject to interindividual variability. Building on a previous transcriptomic-based clustering analysis from an 8-week randomized controlled trial in which 24 individuals consumed 280 g of red raspberries daily, we investigated whether functional metagenomic profiling may enhance our understanding of the observed interindividual variability in metabolic responses. Participants were classified as responders (n = 13) or non-responders (n = 11) based on prior clustering approaches, which identified significant reductions in plasma levels of C-reactive protein (CRP), triglycerides, and total cholesterol in responders. Microbial DNA extracted from fecal samples collected before and after the intervention was sequenced, and carbohydrate-active enzyme (CAZyme) counts were generated using a bioinformatics pipeline. Differential analysis revealed distinct functional metagenomic profiles between responders and non-responders. Multiple linear regressions identified potential associations between baseline CAZyme levels and changes in CRP, with contrasting trends observed between responders and non-responders. CBM8 and CBM49 were among the highlighted CAZymes. GH5 and several GH5 subfamilies were also identified as candidate CAZymes associated with interindividual variability observed in metabolic responses. These findings support the integration of microbiome-derived functional data alongside other omics to improve precision nutrition strategies.