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

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.

Gut Microbiota as Well as Metabolomes of Wistar Rats Recover within Two Weeks after Doripenem Antibiotic Treatment

“…In plasma, 272 semiquantitative metabolites were analyzed using the single peak signal of the respective metabolite and a normalization strategy according to the patent [ 28 ] resulting in fold change ratios representing the metabolite changes in treated versus control animals [ 1 ]. Of these 306 metabolites, the chemical structures of 280 were identified and 26 remained unknown.…”

“…Furthermore, statistical analysis of the metabolome data of plasma and feces matrices, as well as the uploading of these data into our in-house database MetaMapTox ® (or MMT), followed by a PCA analysis were performed following the protocol published by Murali et al 2022 [ 1 , 12 , 13 , 29 ].…”

“…The human gut harbors thousands of different species of bacteria, fungi, archaea, and viruses, where bacteria exceed eukaryotes and archaea by 2–3 orders of magnitude, forming a complex community known as the gut microbiota [ 1 , 2 ]. While intestinal microbiota performs several vital metabolic functions crucial to the host [ 3 , 4 ], its composition is highly variable and susceptible to dysbiosis, which results from pressures such as diet, immune function, environmental chemical exposures, and the use of drugs.…”

“…This makes antibiotics ideal compounds to induce a temporary shift in the gut composition and to determine the changes in metabolic output. In previous studies, we have shown how different classes of antibiotics, including aminoglycosides, fluoroquinolones, lincosamides, and polymyxin E, induce selective changes in the gut microbiome of experimental animals and how these are reflected by antibiotic class-specific changes in the fecal and plasma metabolomes [ 1 , 11 , 12 , 13 ]. Several antibiotics belonging to classes including aminoglycosides, fluoroquinolones, lincosamides, and polymyxin E have been studied to understand their effects on the gut microbiota composition as well as the related metabolic outputs [ 1 , 14 , 15 ].…”

“…In previously published works, the antibiotic classes aminoglycosides, fluoroquinolones, lincosamides, and macrolides and their effects on the gut microbiome were studied [ 1 , 11 , 12 , 15 ]. Here, we expand the previous work by investigating the effects of the carbapenem class.…”