Cohort dependent associations between gut Bacteroides and circulating sphingolipid balance

Abstract Taxonomic and gene-level measurements offer complementary views of microbial contributions to host lipid metabolism. We examined gut Bacteroides abundance, bacterial serine palmitoyltransferase (SPT) gene read abundance and circulating sphingolipids in heart failure and MetaCardis. In 58 patients, the Bacteroides association with the lactosylceramide(16:0)-to-ceramide(16:0) ratio persisted across 85 observations (β = 0.296, P = 0.007). Bacteroides abundance correlated with SPT read abundance (ρ = 0.389, P = 0.0026), but SPT did not improve the adjusted lipid model (likelihood-ratio P = 0.828). The primary MetaCardis analysis did not reproduce the ratio association (n = 544; permutation P = 0.127). An exploratory analysis identified an inverse Bacteroides –lactosylceramide association (n = 972; P = 0.0029). These findings establish a framework for distinguishing cohort-specific taxonomic associations from measured microbial gene abundance and prioritise direct functional validation of microbiome–sphingolipid relationships.