Results indicate that Keystone was safe and well tolerated and selectively modulates the gut microbiome, with exploratory associations for host stress and inflammatory markers that offer key insights for future follow-up studies.
Abstract
The gut microbiome is increasingly recognised as a modifiable contributor to metabolic, immune, and stress-related physiology, yet many nutritional interventions produce broad microbial shifts that may be poorly tolerated. We investigated the effects of a fermented and pasteurised oat-based preparation (Keystone) on microbiome composition and selected biomarkers in a 4-week randomised, double-blind, placebo-controlled trial in generally healthy adults. Seventy-six participants completed the intervention (38 placebo, 38 Keystone). Stool samples collected at baseline and week 4 underwent shotgun metagenomic sequencing, and serum butyrate, IL-8, morning cortisol, albumin/globulin ratio, routine clinical chemistries, DASS-21, and SF-36 were assessed. The intervention did not affect alpha or beta diversity. In contrast, species-level analysis showed a distinct compositional signature, with enrichment of taxa including Akkermansia spp., Bacteroides intestinalis, Bifidobacterium pseudocatenulatum, and Anaerostipes caccae in the Keystone group, alongside lower abundance of several Haemophilus, Megasphaera, and Prevotella taxa relative to placebo (FDR < 0.001). Nominally significant baseline-by-treatment interactions were observed for morning cortisol ( P = 0.03), IL-8 ( P = 0.04), and albumin/globulin ratio ( P = 0.03), while serum butyrate showed a near-significant trend ( P = 0.053). SF-36 emotional well-being improved within the Keystone group. No adverse events were reported. These results indicate that Keystone was safe and well tolerated and selectively modulates the gut microbiome, with exploratory associations for host stress and inflammatory markers that offer key insights for future follow-up studies. Trial registration: The trial was IRB approved and registered with ClinicalTrials.gov NCT07527286.
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