title: Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment.
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.
authors: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
authors: Lara
authors: L
authors: Bull-Otterson
authors: Wenke
authors: W
authors: Feng
authors: Irina
authors: I
authors: Kirpich
authors: Yuhua
authors: Y
authors: Wang
authors: Xiang
authors: X
authors: Qin
authors: Yanlong
authors: Y
authors: Liu
authors: Leila
authors: L
authors: Gobejishvili
authors: Swati
authors: S
authors: Joshi-Barve
authors: Tulin
authors: T
authors: Ayvaz
authors: Joseph
authors: J
authors: Petrosino
authors: Maiying
authors: M
authors: Kong
authors: David
authors: D
authors: Barker
authors: Craig
authors: C
authors: McClain
authors: Shirish
authors: S
authors: Barve
mesh_terms: D000818:Animals; D000891:Anti-Infective Agents, Local / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D044822:Biodiversity; D062445:Claudin-1 / Q000235:genetics; D000431:Ethanol / Q000633:toxicity; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D015870:Gene Expression / Q000187:drug effects; D014644:Genetic Variation; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000382:microbiology*; D052201:Lacticaseibacillus rhamnosus / Q000502:physiology*; D008108:Liver Diseases, Alcoholic / Q000209:etiology / Q000382:microbiology* / Q000628:therapy; D008297:Male; D054892:Metagenome / Q000187:drug effects / Q000235:genetics; D056186:Metagenomics / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D019936:Probiotics / Q000494:pharmacology; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D062826:Zonula Occludens-1 Protein
chemical_list: D000891:Anti-Infective Agents, Local; D062445:Claudin-1; D012336:RNA, Ribosomal, 16S; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D000431:Ethanol