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Integrated Analyses of the Gut Microbiota, Intestinal Permeability, and Serum Metabolome Phenotype in Rats with Alcohol Withdrawal Syndrome.

ABSTRACT: The etiology of alcohol dependence is not completely understood. Increasing evidence reveals that gut microbiota dysbiosis is associated with certain psychiatric disorders, including alcoholism, through the "microbiota-gut-brain" axis. The aims of this study were to evaluate the effect of alcohol abuse on the gut microbiota, intestinal permeability and serum metabolic profile and to determine whether alcohol-induced alterations in gut microbiota are correlated with gut permeability and serum metabolic phenotype changes. 16S rRNA gene high-throughput sequencing and nontarget metabolomics techniques were applied in an alcohol-dependent rat model in the present study. The results showed that alcohol intake altered the composition and structure of the colonic microbiota, especially the relative abundances of commensal microbes in the families Lachnospiraceae and Prevotellaceae, which were significantly decreased. Alcohol-dependent rats developed gut leakiness and a serum metabolic phenotype disorder. The valine, leucine and isoleucine biosynthesis pathways and arginine and proline metabolism pathways were obviously influenced by alcohol intake. Moreover, alcohol consumption disturbed the brain's neurotransmitter homeostasis. Regression analysis showed that alcohol-induced colonic microbiota dysbiosis was strongly associated with increased intestinal permeability and serum metabolic phenotype and neurotransmitter disorders. These results revealed that gut microbiota dysbiosis and serum metabolite alteration might be a cofactor for developing of alcohol dependence. IMPORTANCE Gut microbiota dysbiosis is associated with certain psychiatric disorders through the "microbiota-gut-brain" axis. Here, we revealed that alcohol consumption induced colonic microbiota dysbiosis, increased intestinal permeability, and altered the serum metabolic phenotype in rats, and there was a strong correlation between gut microbiota dysbiosis and serum metabolite disorders. Thus, gut microbiota dysbiosis and serum metabolite alteration may be a cofactor for development of alcohol dependence.

SUBMITTER: Yang F

PROVIDER: S-EPMC8388829 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The etiology of alcohol dependence is not completely understood. Increasing evidence reveals that gut microbiota dysbiosis is associated with certain psychiatric disorders, including alcoholism, through the 'microbiota-gut-brain' axis. The aims were to evaluate the effect of alcohol abuse on the gut microbiota, intestinal permeability and serum metabolic profile and to determine whether alcohol-induced alterations in gut microbiota are correlated with gut permeability and serum metabolic phenotype changes. 16S rRNA gene high-throughput sequencing and nontarget metabolomics techniques were applied in an alcohol-dependent rat model in the present study. The results showed that alcohol intake altered the composition and structure of the colonic microbiota, especially the relative abundance of the commensal microbes Lachnospiraceae and Prevotellaceae, which was significantly decreased. Alcohol-dependent rats developed gut leakiness and a serum metabolic phenotype disorder. The valine, leucine and isoleucine biosynthesis pathways and arginine and proline metabolism pathways were obviously influenced by alcohol intake. Moreover, alcohol consumption disturbed the brain's neurotransmitter homeostasis. The regression analysis showed that alcohol-induced colonic microbiota dysbiosis was strongly associated with increased intestinal permeability and serum metabolic phenotype and neurotransmitter disorders. These results revealed that gut microbiota dysbiosis and serum metabolites alteration might be a cofactor for developing of alcohol dependence. IMPORTANCE The gut microbiota dysbiosis is associated with certain psychiatric disorders through the 'microbiota-gut-brain' axis. Here we revealed that alcohol consumption induced the colonic microbiota dysbiosis, increased intestinal permeability, altered the serum metabolic phenotype in rats, and there were a strong correlation between gut microbiota dysbiosis and serum metabolites disorders. Thus, gut microbiota dysbiosis and serum metabolites alteration may be a cofactor for development of alcohol dependence.

Project description:BackgroundPhosphorus (P) is one of the most essential macronutrients for crops. The growth and yield of peanut (Arachis hypogaea L.) are always limited by P deficiency. However, the transcriptional and metabolic regulatory mechanisms were less studied. In this study, valuable phenotype, transcriptome and metabolome data were analyzed to illustrate the regulatory mechanisms of peanut under P deficiency stress.ResultIn present study, two treatments of P level in deficiency with no P application (-P) and in sufficiency with 0.6 mM P application (+ P) were used to investigate the response of peanut on morphology, physiology, transcriptome, microRNAs (miRNAs), and metabolome characterizations. The growth and development of plants were significantly inhibited under -P treatment. A total of 6088 differentially expressed genes (DEGs) were identified including several transcription factor family genes, phosphate transporter genes, hormone metabolism related genes and antioxidant enzyme related genes that highly related to P deficiency stress. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that 117 genes were annotated in the phenylpropanoid biosynthesis pathway under P deficiency stress. A total of 6 miRNAs have been identified significantly differential expression between + P and -P group by high-throughput sequencing of miRNAs, including two up-regulated miRNAs (ahy-miR160-5p and ahy-miR3518) and four down-regulated miRNAs (ahy-miR408-5p, ahy-miR408-3p, ahy-miR398, and ahy-miR3515). Further, the predicted 22 target genes for 6 miRNAs and cis-elements in 2000 bp promoter region of miRNA genes were analyzed. A total of 439 differentially accumulated metabolites (DAMs) showed obviously differences in two experimental conditions.ConclusionsAccording to the result of transcripome and metabolome analyses, we can draw a conclusion that by increasing the content of lignin, amino acids, and levan combining with decreasing the content of LPC, cell reduced permeability, maintained stability, raised the antioxidant capacity, and increased the P uptake in struggling for survival under P deficiency stress.

Project description:BackgroundAlcoholic liver disease (ALD) is commonly associated with intestinal permeability. An unanswered question is why only a subset of heavy alcohol drinkers develop endotoxemia. Recent studies suggest that circadian disruption is the susceptibility factor for alcohol-induced gut leakiness to endotoxins. The circadian protein PER2 is increased after exposure to alcohol and siRNA knockdown of PER2 in vitro blocks alcohol-induced intestinal barrier dysfunction. We have shown that blocking CYP2E1 (i.e., important for alcohol metabolism) with siRNA inhibits the alcohol-induced increase in PER2 and suggesting that oxidative stress may mediate alcohol-induced increase in PER2 in intestinal epithelial cells. The aim of this study was to elucidate whether a mechanism incited by alcohol-derived oxidative stress mediates the transcriptional induction of PER2 and subsequent intestinal hyperpermeability.MethodsCaco-2 cells were exposed to 0.2% alcohol with or without pretreatment with modulators of oxidative stress or PKA activity. Permeability of the Caco-2 monolayer was assessed by transepithelial electrical resistance. Protein expression was measured by Western blot and mRNA with real-time polymerase chain reaction. Wild-type C57BL/6J mice were fed with alcohol diet (29% of total calories, 4.5% v/v) for 8 weeks. Western blot was used to analyze PER2 expression in mouse proximal colon tissue.ResultsAlcohol increased oxidative stress, caused Caco-2 cell monolayer dysfunction, and increased levels of the circadian clock proteins PER2 and CLOCK. These effects were mitigated by pretreatment of Caco-2 cells with an antioxidant scavenger. Alcohol-derived oxidative stress activated cAMP response element-binding (CREB) via the PKA pathway and increased PER2 mRNA and protein. Inhibiting CREB prevented the increase in PER2 and Caco-2 cell monolayer hyperpermeability.ConclusionsTaken together, these data suggest that strategies to reduce alcohol-induced oxidative stress may alleviate alcohol-mediated circadian disruption and intestinal leakiness, critical drivers of ALD.

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Integrated Analyses of the Gut Microbiota, Intestinal Permeability, and Serum Metabolome Phenotype in Rats with Alcohol Withdrawal Syndrome.

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