Response To Drug May Be Dictated By The Microbiota

The intestinal microbiota is known to modulate bioavailability and efficacy of endogenous compounds, nutrients or drugs, with large interindividual variations.

The least conserved fraction of our microbiota may hence explain a stratification of the human population in converters and non converters for numerous compounds. As an example, the reduction of cholesterol to coprostanol is only active in a fraction of the human population and it is directly associated with the population levels of active Bacteroides dorei (Gerard et al. 2007).

The team of Peter Turnbaugh (Haiser et al. Science 2013) just published that Egghertella lenta, an actinobacterium of the human intestinal microbiota, can metabolize the drug Digoxin, used in cardiac arrest and heart rhythm disorders. E. lenta can reduce Digoxin to an inactive form and differences in populations of metabolizing E. lenta would explain the heterogeneity observed in response to drug therapy between patients. Using gnotobiotic laboratory animals, they further showed that reduction of Digoxin by E. lenta can be modulated by diet. High dietary proteins will noticeably rise levels of arginin, that will in turn limit inactivation of Digoxin.

This work underlines how important it may be to consider the activity of our symbiotic microbiota in the pharmacological evaluation of the response of patients to certain drugs. One may even foresee that microbiota profiling will allow in the future to predict response to drugs and become part of the resources for clinical management.

 

  • Philippe Gérard, Pascale Lepercq, Marion Leclerc, Françoise Gavini, Pierre Raibaud and Catherine Juste. 2007. Bacteroides sp. Strain D8, the First Cholesterol-Reducing Bacterium Isolated from Human Feces. Appl Environ Microbiol. 73:5742–5749.
  • Henry J. Haiser, David B. Gootenberg, Kelly Chatman, Gopal Sirasani, Emily P. Balskus, Peter J. Turnbaugh. 2013. Predicting and Manipulating Cardiac Drug Inactivation by the Human Gut Bacterium Eggerthella lenta. Science 131:295-298.
Fernando Aspiroz
Fernando Aspiroz