Gut microbiota-derived imidazole propionate is associated with obesity.

Obesity is a progressive metabolic disorder with some well-recognized markers, such as increased or elevated branched-chain amino acids (BCAAs). However, the role of gut microbiota-derived metabolites remains unknown in Asian populations. By employing an integrated multi-omics approach combining metagenomic and plasma metabolomic profiling in an Asian cohort alongside a longitudinal analysis of a bariatric surgery subgroup. We identified a distinct metabolic signature in obesity characterized by depleted circulating histidine and a concomitant elevation of Imidazole Propionate (ImP). The elevated ImP level not only positively correlated with the body mass index (BMI) but also increased progressively across obesity severity categories, and were associated with the taxonomic enrichment of ImP-producing species, such as Streptococcus mutans and Lactobacillus gasseri. Meanwhile, the ImP level showed rapid reduction within 3 months post-bariatric surgery. Collectively, our findings indicate that gut dysbiosis and histidine metabolism toward ImP production link with obesity and metabolic dysfunction.