Work

A prescription-computable pharmaco-ecological exposure score for predicted drug-induced gut-microbiome disturbance and its association with heart failure in chronic kidney disease

Year: 2026

Type: article

Abstract: Polypharmacy is pervasive in chronic kidney disease (CKD); however, the cumulative burden of non-antibiotic drugs on the gut microbiota is not captured by host-centric medication indices and is rarely measurable at scale. We developed the cumulative disturbance score (CDS), a prescription-computable exposure metric that scores the predicted drug-induced disturbance of 40 core gut taxa, integrating in vitro growth-inhibition data for 1,197 drugs with duration-weighted prescription records. In 179,591 patients with incident CKD, a higher CDS for a core taxon was associated with incident heart failure in weighted Cox models. Using the internally estimated polypharmacy (≥ 8 drugs) hazard ratio 1.228 as the selection rule, four taxa were prioritized ( Bacteroides fragilis enterotoxigenic, Eggerthella lenta , Bacteroides vulgatus , and Bacteroides uniformis ; 1.262–1.286), whereas a negative-control taxon was null. Taxon-level effects are not separately identified, the scores deriving from shared prescription histories. Whether the association reflects microbial mediation or residual confounding by disease severity cannot be determined without microbiome measurement. Empirical calibration against 15 negative-control outcomes attenuated the estimates to 1.111–1.157. Chronically prescribed cardiovascular and gastrointestinal agents contributed most for Bacteroides taxa, antibacterials for E. lenta . CDS is a prescription-level exposure indicator instead of a microbiome measurement: a scalable pharmaco-ecological index for prioritizing drug–microbiome risks, applied here to heart failure in CKD.

Source: Scientific Reports

DOI: 10.1038/s41598-026-76828-8