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.
If it is a certain strain of bacteria that makes acarbose ineffective, it would make sense that you could take an antibiotic that targets that bacteria and then take a probiotic to replenish your gut with good bacteria. This would then make acarbose effective again. Would this work?
Currently, most antibiotics are broad-spectrum antibiotics, which can have a devastating effect on your gut microbiota, as they do not target specific bacteria for suppression.
Kleb. G. Is not a normal part of the gut flora. Don’t know if you’d want to risk creating a drug resistant form.