Abstract
The gut microbiome is vital to the health and development of an organism, specifically in determining the host response to a chemical (drug) administration. To understand this, we investigated the effects of six antibiotic (AB) treatments (Streptomycin sulfate, Roxithromycin, Sparfloxacin, Vancomycin, Clindamycin and Lincomycin hydrochloride) and diet restriction (–20%) on the gut microbiota in 28-day oral toxicity studies on Wistar rats. The fecal microbiota was determined using 16S rDNA marker gene sequencing. AB-class specific alterations were observed in the bacterial composition, whereas restriction in diet caused no observable difference. These changes associated well with the changes in the LC–MS/MS- and GC–MS-based metabolome profiles, particularly of feces and to a lesser extent of plasma. Particularly strong and AB-specific metabolic alterations were observed for bile acids in both plasma and feces matrices. Although AB-group-specific plasma metabolome changes were observed, weaker associations between fecal and plasma metabolome suggest a profound barrier between them. Numerous correlations between the bacterial families and the fecal metabolites were established, providing a holistic overview of the gut microbial functionality. Strong correlations were observed between microbiota and bile acids, lipids and fatty acids, amino acids and related metabolites. These microbiome–metabolome correlations promote understanding of the functionality of the microbiome for its host.
Highlights
The gut microbiome plays an essential role in host health and well-being by maintaining physiological homeostasis [1]
Males treated with Clindamycin showed slight salivation, semi-closed eyelid and, two of them were in poor condition
Animals treated with the lincosamide antibiotics Clindamycin and Lincomycin, showed very similar changes in bacterial communities, demonstrating a clear antibiotic class-dependent effect as they are selectively effective against staphylococci, streptococci and most anaerobic bacteria [34]
Summary
The gut microbiome plays an essential role in host health and well-being by maintaining physiological homeostasis [1]. Bacterial cells are present in the human gut by 2–3 orders of magnitude more compared to the eukaryotes and archaea [3]. The gut flora is altered by several factors including host health, medication, environment, diet, age, host genetics, and immune system [4,5]. Host diet and antibiotic usage have important influences in altering the composition of the gut microbiome [6]. Zimmermann et al, 2019 provided an outline of the drug-metabolizing activity of human gut bacteria and discovered that about 2/3 of the drugs are metabolized by at least one bacterial strain [4]
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