Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment.

TitleMetagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment.
Publication TypeJournal Article
Year of Publication2013
AuthorsBull-Otterson, L, Feng, W, Kirpich, I, Wang, Y, Qin, X, Liu, Y, Gobejishvili, L, Joshi-Barve, S, Ayvaz, T, Petrosino, J, Kong, M, Barker, D, McClain, C, Barve, S
JournalPLoS One
Volume8
Issue1
Paginatione53028
Date Published2013
ISSN1932-6203
KeywordsAnimals, Anti-Infective Agents, Local, Bacteria, Biodiversity, Claudin-1, Ethanol, Feces, Gene Expression, Genetic Variation, Hydrogen-Ion Concentration, Intestines, Lactobacillus rhamnosus, Liver Diseases, Alcoholic, Male, Metagenome, Metagenomics, Mice, Mice, Inbred C57BL, Probiotics, Reverse Transcriptase Polymerase Chain Reaction, RNA, Ribosomal, 16S, Sequence Analysis, DNA, Species Specificity, Zonula Occludens-1 Protein
Abstract

Enteric dysbiosis plays an essential role in the pathogenesis of alcoholic liver disease (ALD). Detailed characterization of the alterations in the gut microbiome is needed for understanding their pathogenic role in ALD and developing effective therapeutic approaches using probiotic supplementation. Mice were fed liquid Lieber-DeCarli diet without or with alcohol (5% v/v) for 6 weeks. A subset of mice were administered the probiotic Lactobacillus rhamnosus GG (LGG) from 6 to 8 weeks. Indicators of intestinal permeability, hepatic steatosis, inflammation and injury were evaluated. Metagenomic analysis of the gut microbiome was performed by analyzing the fecal DNA by amplification of the V3-V5 regions of the 16S rRNA gene and large-scale parallel pyrosequencing on the 454 FLX Titanium platform. Chronic ethanol feeding caused a decline in the abundance of both Bacteriodetes and Firmicutes phyla, with a proportional increase in the gram negative Proteobacteria and gram positive Actinobacteria phyla; the bacterial genera that showed the biggest expansion were the gram negative alkaline tolerant Alcaligenes and gram positive Corynebacterium. Commensurate with the qualitative and quantitative alterations in the microbiome, ethanol caused an increase in plasma endotoxin, fecal pH, hepatic inflammation and injury. Notably, the ethanol-induced pathogenic changes in the microbiome and the liver were prevented by LGG supplementation. Overall, significant alterations in the gut microbiome over time occur in response to chronic alcohol exposure and correspond to increases in intestinal barrier dysfunction and development of ALD. Moreover, the altered bacterial communities of the gut may serve as significant therapeutic target for the prevention/treatment of chronic alcohol intake induced intestinal barrier dysfunction and liver disease.

DOI10.1371/journal.pone.0053028
Alternate JournalPLoS ONE
PubMed ID23326376
PubMed Central IDPMC3541399
Grant ListP01 AA017103 / AA / NIAAA NIH HHS / United States
P30 AA019360 / AA / NIAAA NIH HHS / United States
R01 AA0015970 / AA / NIAAA NIH HHS / United States
R01 AA018016 / AA / NIAAA NIH HHS / United States
R01 AA018869 / AA / NIAAA NIH HHS / United States
R01 AA018869 / AA / NIAAA NIH HHS / United States
R01 AAO14371 / / PHS HHS / United States
R01 DK071765 / DK / NIDDK NIH HHS / United States
R21 AA020849 / AA / NIAAA NIH HHS / United States
R37 AA010762 / AA / NIAAA NIH HHS / United States
RC2AA019385 / AA / NIAAA NIH HHS / United States