Inactivation of the antidiabetic drug acarbose by human intestinal microbial-mediated degradation
Date:2023-06-03 clicks:
Impact Factor:19.889
Journal:Nature Metabolism
Abstract:Drugs can be modified or degraded by the gut microbiota, which needs to be considered in personalized therapy. The clinical efficacy of the antidiabetic drug acarbose, an inhibitor of α-glucosidase, varies greatly among individuals for reasons that are largely unknown. Here we identify in the human gut acarbose-degrading bacteria, termed Klebsiella grimontii TD1, whose presence is associated with acarbose resistance in patients. Metagenomic analyses reveal that the abundance of K. grimontii TD1 is higher in patients with a weak response to acarbose and increases over time with acarbose treatment. In male diabetic mice, co-administration of K. grimontii TD1 reduces the hypoglycaemic effect of acarbose. Using induced transcriptome and protein profiling, we further identify an acarbose preferred glucosidase, Apg, in K. grimontii TD1, which can degrade acarbose into small molecules with loss of inhibitor function and is widely distributed in human intestinal microorganisms, especially in Klebsiella. Our results suggest that a comparatively large group of individuals could be at risk of acarbose resistance due to its degradation by intestinal bacteria, which may represent a clinically relevant example of non-antibiotic drug resistance.
Co-author:Peijun Yu,Ying Xin,Fengmei Xu,Lianwei Wang,Yahui Mu,Xiangyang Guo,Qiang Sun,Guoping Zhao
First Author:Jinzhong Tian,Chong Li,Zhixiang Dong,Yunpeng Yang,Jing Xing
Indexed by:SCI一区TOP
Correspondence Author:Yang Gu,Guijun Qin,Weihong Jiang
Discipline:Natural Science
First-Level Discipline:Biology
Document Type:SCI
Volume:5
Issue:5
Page Number:896-909
Translation or Not:no
Date of Publication:2023-05-08
Included Journals:SCI
Links to published journals:https://www.nature.com/articles/s42255-023-00796-w
