Helicobacter pylori may be the most successful pathogen in human history. While not as deadly as the bacteria that cause tuberculosis, cholera, and the plague, it infects more people than all the others combined. H. pylori, which migrated out of Africa along with our ancestors, has been intertwined with our species for at least two hundred thousand years. Although the bacterium occupies half the stomachs on earth, its role in our lives was never clear. Then, in 1982, to the astonishment of the medical world, two scientists, Barry Marshall and J. Robin Warren, discovered that H. pylori is the principal cause of gastritis and peptic ulcers; it has since been associated with an increased risk of stomach cancer as well. Until that discovery, for which the men shared a Nobel Prize, in 2005, stress, not an infection, was assumed to be the major cause of peptic ulcers.
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