Digoxin-inactivating bacteria: identification in human gut flora.

Area of Science:

• Pharmacology and Microbiology
• Gastrointestinal Metabolism

Background:

• Digoxin, a widely used cardiac glycoside, is often metabolized into cardioinactive forms.
• This metabolic conversion, involving lactone ring reduction, primarily occurs in the gastrointestinal tract.
• The specific microorganisms responsible for this digoxin inactivation pathway have not been definitively identified.

Purpose of the Study:

• To isolate and identify microorganisms capable of reducing digoxin from human stool cultures.
• To investigate the role of specific gut flora in the metabolic inactivation of digoxin in vivo.

Main Methods:

• Culturing stool samples from human volunteers to isolate anaerobic bacteria.
• Testing isolated bacterial strains for their ability to reduce digoxin.
• Administering digoxin to human volunteers and analyzing stool for metabolites.
• Manipulating the growth of Eubacterium lentum using arginine.

Main Results:

• Eubacterium lentum was identified as the sole organism among hundreds of isolates capable of reducing digoxin.
• High concentrations of E. lentum were found in individuals who did not excrete digoxin metabolites in vivo.
• Stimulating E. lentum growth with arginine inhibited digoxin inactivation.
• Neither the presence nor the concentration of E. lentum alone determined digoxin inactivation in vivo.

Conclusions:

• Eubacterium lentum is a key player in the gastrointestinal reduction of digoxin.
• The metabolic inactivation of digoxin is not solely dependent on the presence or quantity of E. lentum.
• Further research is needed to understand the complex factors influencing digoxin metabolism in the gut.