TB Research

The Dysbiosis Triggered by First-Line Tuberculosis Antibiotics Fails to Reduce Their Bioavailability

Sivaranjani Namasivayam, Matthew Zimmerman, Sandra D. Oland, Han Wang, Lara Mittereder, Véronique Dartois, Alan Sher

mBio · 2023-03

Abstract

Previous studies have shown that treatment of Mycobacterium tuberculosis infection with first-line antibiotics results in a long-lasting disruption of the host microbiota. Since the microbiome has been shown to influence the host availability of other drugs, we employed a mouse model to ask whether the dysbiosis resulting from either tuberculosis (TB) chemotherapy or a more aggressive course of broad-spectrum antibiotics might influence the pharmacokinetics of the TB antibiotics themselves. While drug exposure was not reduced in animals previously described as exhibiting the dysbiosis triggered by conventional TB chemotherapy, we found that mice with other alterations in the microbiome, such as those triggered by more intensive antibiotic treatment, displayed decreased availability of rifampicin and moxifloxacin, which in turn could impact their efficacy. The above findings are relevant not only to TB but also to other bacterial infections treated with these two broader spectrum antibiotics.

MeSH terms

  • Pyrazinamide
  • Rifampicin
  • Antibiotics
  • Bioavailability
  • Isoniazid
  • Pharmacology
  • Moxifloxacin
  • Medicine
  • Rifamycin
  • Dysbiosis
  • Gut flora
  • Tuberculosis
  • Microbiology