The impact of the intestinal microbiota and the mucosal permeability on three different antibiotic drugs

Eur J Pharm Sci. 2021 Sep 1:164:105869. doi: 10.1016/j.ejps.2021.105869. Epub 2021 May 18.

Abstract

BackgroundThe totality of bacteria, protozoa, viruses and fungi that lives in the human body is called microbiota. Human microbiota specifically colonizes the skin, the respiratory and urinary tract, the urogenital tract and the gastrointestinal system. This study focuses on the intestinal microbiota to explore the drug-microbiota relationship and, therefore, how the drug bioavailability changes in relation to the microbiota biodiversity to identify more personalized therapies, with the minimum risk of side effects. MethodsTo achieve this goal, we developed a new mathematical model with two compartments, the intestine and the blood, which takes into account the colonic mucosal permeability variation - measured by Ussing chamber system on human colonic mucosal biopsies - and the fecal microbiota composition, determined through microbiota 16S rRNA sequencing analysis. Both of the clinical parameters were evaluated in a group of Irritable Bowel Syndrome patients compared to a group of healthy controls. Key ResultsThe results show that plasma drug concentration increases as bacterial concentration decreases, while it decreases as intestinal length decreases too. ConclusionsThe study provides interesting data since in literature there are not yet mathematical models with these features, in which the importance of intestinal microbiota, the "forgotten organ", is considered both for the subject health state and in the nutrients and drugs metabolism.

Keywords: Compartmental models; Drug bioavailability; Gut barrier function; Intestinal microbiota.

MeSH terms

  • Anti-Bacterial Agents
  • Feces
  • Gastrointestinal Microbiome*
  • Humans
  • Intestinal Mucosa
  • Permeability
  • Pharmaceutical Preparations*
  • RNA, Ribosomal, 16S / genetics

Substances

  • Anti-Bacterial Agents
  • Pharmaceutical Preparations
  • RNA, Ribosomal, 16S