System-level gut microbial functional dysregulation in treatment-naive chronic constipation and its reshaping by prune intervention
We conducted large-scale shotgun metagenomic sequencing of treatment-naive adults with chronic constipation and healthy controls, all free of comorbidities and medication use. Chronic constipation was associated with suppression of microbial carbohydrate metabolism, including pectin degradation, central carbon metabolism, and short-chain fatty acid production, together with altered bifid shunt-mediated carbon flux, GABA shunt, and hydrogen consumption, including methanogenesis. Additional perturbations in amino acid metabolism, bile acid metabolism, and microbial structural features indicated system-level metabolic dysfunction of the gut microbiome. We further conducted a randomized, double-blind prune intervention in the same cohort. In contrast to placebo, prune intake improved constipation symptoms and selectively restored the sequential processes from carbohydrate uptake to fermentation, reduced methanogenesis, and shifted constipation-associated microbial taxa toward a healthy reference state. This study reframes chronic constipation as a disorder driven by dysregulated host-microbial metabolic crosstalk that can be partially reshaped by natural food-based intervention.