Chronic Ethanol Consumption Alters Mammalian Gastrointestinal Content Metabolites

Abstract

Chronic ethanol consumption is not only associated with the alteration of metabolic profiles in biofluids, but also the composition of the gut microbiome. Our understanding of the importance of the intestinal microbiota as well as the disturbances elicited by ethanol intervention is limited by the fact that previous analyses have primarily focused on biofluids and liver tissue metabolome; the metabolic profiles of the gastrointestinal (GI) contents are rarely investigated. In this study, we applied a metabonomics approach using a high performance liquid chromatography time of flight mass spectrometry (HPLC-TOFMS) and gas chromatography mass spectrometry (GC-MS) to characterize the metabolic alterations of the contents within the GI tract (stomach, duodenum, jejunum, ileum, cecum, colon, and rectum) in male Sprague Dawley rats following 8 weeks ethanol exposure. We obtained a snapshot of the distinct changes of the intestinal content metabolite composition in rats with ethanol exposure, which indicated a profound impact of ethanol consumption on the intestinal metabolome. Many metabolic pathways that are critical for host physiology were affected, including markedly altered bile acids, increased fatty acids and steroids, decreased carnitines and metabolites involved in lipid metabolism, a significant decrease of all amino acids and branched chain amino acids, and significantly decreased short chain fatty acids except for acetic acid which rapidly elevated as a product of ethanol metabolism. These results provide an improved understanding of the systemic alteration of intestinal metabolites in mammals and the interplay between the host and its complex resident microbiota, and may aid in the design of new therapeutic strategies that target these interactions.

Alcoholic Hepatitis: Risk Factors, Pathogenesis, and Approach to Treatment

“…Chronic alcohol use also changes the metabolic composition of the gastrointestinal tract and decreases the diversity of the microbiome (Szabo, 2015;Xie et al, 2013). This combination of intestinal dysbiosis and interrupted gut mucosal barrier results in increased translocation of bacterial LPS (Hartmann et al, 2015;Wang et al, 2012).…”

Global Metabolic Profiling for The Study of Alcohol-Related Disorders

“…The profiling technique that has been most applied for global metabolite profiling in the case of ethanol is LC-MS, particularly the combination of UPLC with TOF-MS [25][26][27][28][29][30][31][32][33], followed by 1 H NMR spectroscopy [34][35][36][37][38][39][40], with a single study that employed GC-MS [41]. In Tables 1 & 2 the metabolite profiling methods by NMR or LC-MS, respectively, are summarized.…”

“…Most of the published work on metabolomics for the study of alcohol-related metabolic dysfunctions relate to the ana lysis of urine or liver samples of rodents (rats or mice of different strains, wild type or transgenic) [25][26][27][28]30,31,[34][35][36][37][38][39]41] with limited reports describing metabolic profiling of brain, serum or plasma [29,30,33,34,[36][37][38]; there are also two recent studies on pancreatic tissue and the GI tract [32,40]. In the majority of studies in rodents, the alcohol was administered via oral gavage or in the animals drinking water [25,29,31,32,34,36,40,41] [26,27,35,37,38].…”

“…In the majority of studies in rodents, the alcohol was administered via oral gavage or in the animals drinking water [25,29,31,32,34,36,40,41] [26,27,35,37,38]. In some cases, the intragastric feeding model was also adopted [28,30], allowing a controlled 24 h a day delivery of ethanol that provides a robust and repeatable model of ethanol exposure.…”

“…An LC-MS-based study has recently investigated the effects of ethanol exposure on the metabolic profiles of regions of the GI tract [32]. Alterations in the intestinal microbiome, which is known to be important for host homeostasis and is implicated in the development of a variety of diseases, with exogenous interventions in general and more specifically with alcohol abuse are well known [46].…”