Antibiotic-Induced Changes in Microbiome-Related Metabolites and Bile Acids in Rat Plasma.

Véronique de Bruijn,Karsten Beekmann,Markus Slopianka,Volker Haake,Saskia Sperber,Bennard van Ravenzwaay,Philipp Ternes,Christina Behr,Tilmann Walk

doi:10.3390/metabo10060242

Véronique de Bruijn, Karsten Beekmann + Show 7 more

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https://doi.org/10.3390/metabo10060242

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Abstract

Various environmental factors can alter the gut microbiome’s composition and functionality, and modulate host health. In this study, the effects of oral and parenteral administration of two poorly bioavailable antibiotics (i.e., vancomycin and streptomycin) on male Wistar Crl/Wi(Han) rats for 28 days were compared to distinguish between microbiome-derived or -associated and systemic changes in the plasma metabolome. The resulting changes in the plasma metabolome were compared to the effects of a third reference compound, roxithromycin, which is readily bioavailable. A community analysis revealed that the oral administration of vancomycin and roxithromycin in particular leads to an altered microbial population. Antibiotic-induced changes depending on the administration routes were observed in plasma metabolite levels. Indole-3-acetic acid (IAA) and hippuric acid (HA) were identified as key metabolites of microbiome modulation, with HA being the most sensitive. Even though large variations in the plasma bile acid pool between and within rats were observed, the change in microbiome community was observed to alter the composition of the bile acid pool, especially by an accumulation of taurine-conjugated primary bile acids. In-depth investigation of the relationship between microbiome variability and their functionality, with emphasis on the bile acid pool, will be necessary to better assess the potential adverseness of environmentally induced microbiome changes.

Highlights

The gut microbiome consists of around 1000 species of bacteria, fungi, archaea and viruses [1] and is increasingly recognized to play a central role in host health
Our results indicate that Indole-3-acetic acid (IAA) is the most sensitive indole-derivatized indicator of gut microbial modulation, as it was clearly downregulated after parenteral roxithromycin treatment
The current results demonstrate that oral roxithromycin and vancomycin treatment decreased the levels of primary bile acids, while the taurine conjugates of primary bile acids were increased with oral administration of all three antibiotics and parenteral roxithromycin administration

Summary

Introduction

The gut microbiome consists of around 1000 species of bacteria, fungi, archaea and viruses [1] and is increasingly recognized to play a central role in host health. Co-evolution of the host with the gut microbiome has resulted in a close host-microbiome interplay and mutual co-dependency. The host body is crucial for the survival of the gut microbiome, whereas the microbiome plays a role in many metabolic processes required for host health and well-being [2]. Environmental factors can affect the composition and functionality of the microbiome. The gut microbiome is comprised of bacterial, archaeal, viral and fungal species. Alterations in the microbial composition can alter the microbiome’s functionality, i.e., the metabolites produced by the microbiome which are subsequently absorbed by the host, and metabolomics can be used to assess these changes [3]

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