Heparin and its derivative are commonly used as injectable anticoagulants in clinical, but with poor oral bioavailability. To explore the role of the gut microbiota in the poor oral effect of heparin, the degradation profiles of heparin by six human gut microbiota were investigated. The heparin-degradation ability varied significantly among individuals. Furthermore, two strains of heparin-degrading bacteria, Bacteroides ovatus A2 and Bacteroides cellulosilyticus B19 were isolated from different individual’s gut microbiota and the degradation products of the isolates were profiled. The ΔUA2S-GlcNS6S was the major end product, almost no desulfation. 3-O-sulfo group-containing tetrasaccharides were detected, which indicated that the antithrombin binding site was broken and explained the lost anticoagulant activity of heparin. Collectively, the present study assessed the degradation profiles of heparin by human gut microbiota and provided references for the development of oral administration of heparin from a gut microbiota perspective.

肝素及其衍生物在临床上常用作注射用抗凝剂，但口服生物利用度较差。为了探索肠道微生物群在肝素口服效果不佳中的作用，研究了六种人类肠道微生物群对肝素的降解情况。肝素降解能力因人而异。此外，从不同个体的肠道微生物群中分离出两株肝素降解细菌，卵形拟杆菌A2 和纤维素类拟杆菌B19，并对分离物的降解产物进行了分析。ΔUA2S-GlcNS6S 是主要的最终产品，几乎没有脱硫。3- O检测到含-磺基的四糖，表明抗凝血酶结合位点被破坏，解释了肝素失去抗凝活性。总的来说，本研究评估了人类肠道微生物群对肝素的降解情况，并为从肠道微生物群的角度开发口服肝素提供了参考。