Effect of Antibiotic Treatment on the Intestinal Metabolome

Abstract

The importance of the mammalian intestinal microbiota to human health has been intensely studied over the past few years. It is now clear that the interactions between human hosts and their associated microbial communities need to be characterized in molecular detail if we are to truly understand human physiology. Additionally, the study of such host-microbe interactions is likely to provide us with new strategies to manipulate these complex systems to maintain or restore homeostasis in order to prevent or cure pathological states. Here, we describe the use of high-throughput metabolomics to shed light on the interactions between the intestinal microbiota and the host. We show that antibiotic treatment disrupts intestinal homeostasis and has a profound impact on the intestinal metabolome, affecting the levels of over 87% of all metabolites detected. Many metabolic pathways that are critical for host physiology were affected, including bile acid, eicosanoid, and steroid hormone synthesis. Dissecting the molecular mechanisms involved in the impact of beneficial microbes on some of these pathways will be instrumental in understanding the interplay between the host and its complex resident microbiota and may aid in the design of new therapeutic strategies that target these interactions.

In-feed antibiotic effects on the swine intestinal microbiome

“…Antibiotics are thought to improve feed efficiency in agricultural animals primarily by decreasing the bacterial load, which is beneficial to the host by reducing competition for nutrients and decreasing the host's cost of responding to the microbes (2). Analysis of the swine metabolome after antibiotic treatment showed an effect on various biosynthetic pathways, including sugar, fatty acid, bile acid, and steroid hormone synthesis (33). COGs may therefore be useful signposts for identifying microbes and functions important to the performance-enhancing effects of antibiotics like ASP250.…”

Distinct signatures of host–microbial meta-metabolome and gut microbiome in two C57BL/6 strains under high-fat diet

“…Most of the metabolomics studies relevant in the research of obesity were performed with body fluids that cover only a small subset of metabolites (Xie et al, 2012). Only few metabolomics studies applied MS based techniques to investigate the metabolite patterns in intestinal/fecal and liver samples following exposure to different diets and disease conditions to discover the role and influence on the metabolome as a readout (Jansson et al, 2009;Antunes et al, 2011;Baur et al, 2011;Swann et al, 2011;Matsumoto et al, 2012). This study is performed by using two C57BL/6 mouse strains (C57BL/6J (C57J) and C57BL/6N (C57N)) exposed to a high-fat diet (HFD) for 3 weeks.…”

High-resolution time-of-flight mass spectrometry fingerprinting of metabolites from cecum and distal colon contents of rats fed resistant starch

“…The PLS-DA classification was able only to modestly separate distal colon antibiotic and saline subgroup treatments. It has been observed that antibiotics have a profound effect on the microbial gut community and metabolic processes in mice [42]. A cultured gut microbial community can return to pre-antibiotic treatment levels approximately 3 weeks after treatment [53,54].…”

“…The metabolite extraction was an adaption of the method of Antunes et al [42]. Frozen cecal and distal colon samples were thawed and approximately 150 mg of sample was placed in a 2.0-mL microcentrifuge tube (Eppendorf, Hamburg, Germany).…”

“…Work performed with CE and LC-MS has attempted to identify metabolites using standard retention time libraries and elemental formulas from accurate mass measurements [40]. Ultrahigh resolution mass spectrometry using Fourier transform ion cyclotron resonance instruments has been used for metabolite analysis [41,42]. Even matrix-assisted laser desorption ionization imaging has recently been coupled with mass spectrometry to obtain metabolite insight [43].…”