Function-based personalization of dietary fiber selection enhances gut microbial fermentation: a proof-of-concept crossover trial.

UNLABELLED: Text Responses to dietary fiber supplementation vary markedly among individuals, yet no validated platform exists to prospectively identify optimal fiber types based on individual gut microbiome function. Here we present My Dietary Fiber Finder (MyDFF), an ex vivo functional screening platform that predicts optimal dietary fibers for individual gut microbiomes through direct fermentation profiling. For each participant, the dietary fiber with the highest saccharification index (SI) was designated M-PDF, and that with the lowest SI was designated L-PDF. In a crossover trial involving eight healthy Japanese adults (72 longitudinal observations, each participant serving as their own control), the pre-specified per-participant analysis (Dunnett's test) showed that M-PDF significantly increased fecal volatile fatty acid (VFA; acetate + propionate + butyrate) concentrations over baseline in two of eight participants and total short-chain fatty acid (SCFA) concentrations in one, whereas the non-personalized fiber (L-PDF) did so in none. Post hoc group-level analysis confirmed a significant increase over baseline for M-PDF (total VFA and total SCFA, both p < 0.01) but not for L-PDF, and in a within-participant comparison M-PDF exceeded L-PDF in seven of eight participants (mean difference = 32.4 μmol/g; 95% CI: 8.7-56.1; p = 0.014; Cohen's d = 1.14). However, the magnitude of the pre-intervention saccharification-index differential between the two fibers did not significantly correlate with the magnitude of the in vivo VFA response differential across participants (Pearson r = 0.082, p = 0.85), indicating that the assay did not quantitatively predict response magnitude. Exploratory 16S rRNA gene sequencing analysis showed no significant cohort-level shift in overall gut microbial community composition during either intervention phase. In four separate validation donors, individual fermentation profiles remained relatively stable over the observed 3-9-month follow-up. These proof-of-concept findings support the potential of function-based framework for personalized prebiotic design and motivate larger validation studies. CLINICAL TRIAL REGISTRATION: https://jrct.niph.go.jp, identifier jRCTs051220163.