Leaky gut
ALD is preceded by leaky gut, which is both directly and indirectly caused by alcohol consumption. Alcohol is fermented in the gut and produces acetaldehyde, which disrupts the tight junctions that hold the intestinal cells together (Llorente and Schnabl 2015). In addition to this, alcohol causes leaky gut by inducing inflammation (Chart 1). Alcohol and bacteria “cooperate” to cause inflammation of the bowel and the liver that causes the gut to become more permeable. Wang et al., (2013) demonstrated in mice models that bacteria cells and bacterial products translocate into the portal vein via the leaks created by the acetaldehyde, the product of ethanol fermentation in the colon, before and after dysbiosis occurs. Lipopolysaccharides and flagellin are protein ligands present on and around Gram-negative bacteria that would be among those translocating, and they bind to toll like receptor (TRL) 4 and TLR5 on macrophages in the portal vein and Kupffer cells in the liver of mice (Wang et al., 2013; Jarvelainen et al., 2000). The alcohol opens a pathway for the bacteria to travel into the portal vein where they are detected by the host’s immune system due to the bacteria’s identifying proteins. The binding of bacterial proteins and TRLs begins a cascade inducing pro-inflammatory tumor necrosis factor alpha (TNFα) to release into the blood plasma (Jarvelainen et al., 2000). The TNFα induces inflammation in the mice liver and intestinal cells, causing the intestinal wall to become more permeable or “leaky” (Wang et al., 2013). This is a positive feedback loop in which the leaky gut allows bacteria to enter the blood stream where they are detected by immune cells that induce inflammation, which in turn makes the intestine leak more, allowing more bacteria to translocate and cause more inflammation (Chart 1; Figure 1). The inflammation also induced the release of reactive oxygen species (ROS) into the plasma and intestine; that leads to more inflammation (and therefore more ROS) by activating nuclear factor κB (NF κB) in cells and producing another positive feedback loop. ROS are typically regulated by nuclear factor erythroid 2-related factor 2 (Nrf2) in cells, but alcohol inhibits the production of Nrf2, allowing ROS concentrations to rise. And due to another effect of alcohol, the intestine cannot be repaired during this. Wang et al., (2013) demonstrated that alcohol inhibits the transcription of bacterial proteins that metabolize long chain triglycerols to LCFAs, the major energy source for Lactobacillus. Lactobacillus produces compounds that inhibit the inflammation proliferating leaky gut as well as compounds necessary for tight junction formation; therefore without LCFAs, Lactobacillus is unable to reduce or repair leaky gut (Wang et al., 2013). In short: alcohol causes leaky gut with both direct pathways, such as the disruption of intestinal cell tight junctions, and indirect pathways, such as the positive feedback loop …show more content…
Alcohol’s fermented state disrupts the tight joints of the intestinal wall, allowing ligands to enter the portal vein that trigger the immune system to inflame the area, resulting in increased intestinal permeability and a positive feedback loop of inflammation that cannot be corrected by Lactobacillus due to the alcohol inhibiting the synthesis of LCFAs that Lactobacillus needs to function (Llorente and Schnabl, 2015; Wang et al., 2013). Alcohol also causes fat build-ups in the liver, commonly referred to as fatty
ALD is preceded by leaky gut, which is both directly and indirectly caused by alcohol consumption. Alcohol is fermented in the gut and produces acetaldehyde, which disrupts the tight junctions that hold the intestinal cells together (Llorente and Schnabl 2015). In addition to this, alcohol causes leaky gut by inducing inflammation (Chart 1). Alcohol and bacteria “cooperate” to cause inflammation of the bowel and the liver that causes the gut to become more permeable. Wang et al., (2013) demonstrated in mice models that bacteria cells and bacterial products translocate into the portal vein via the leaks created by the acetaldehyde, the product of ethanol fermentation in the colon, before and after dysbiosis occurs. Lipopolysaccharides and flagellin are protein ligands present on and around Gram-negative bacteria that would be among those translocating, and they bind to toll like receptor (TRL) 4 and TLR5 on macrophages in the portal vein and Kupffer cells in the liver of mice (Wang et al., 2013; Jarvelainen et al., 2000). The alcohol opens a pathway for the bacteria to travel into the portal vein where they are detected by the host’s immune system due to the bacteria’s identifying proteins. The binding of bacterial proteins and TRLs begins a cascade inducing pro-inflammatory tumor necrosis factor alpha (TNFα) to release into the blood plasma (Jarvelainen et al., 2000). The TNFα induces inflammation in the mice liver and intestinal cells, causing the intestinal wall to become more permeable or “leaky” (Wang et al., 2013). This is a positive feedback loop in which the leaky gut allows bacteria to enter the blood stream where they are detected by immune cells that induce inflammation, which in turn makes the intestine leak more, allowing more bacteria to translocate and cause more inflammation (Chart 1; Figure 1). The inflammation also induced the release of reactive oxygen species (ROS) into the plasma and intestine; that leads to more inflammation (and therefore more ROS) by activating nuclear factor κB (NF κB) in cells and producing another positive feedback loop. ROS are typically regulated by nuclear factor erythroid 2-related factor 2 (Nrf2) in cells, but alcohol inhibits the production of Nrf2, allowing ROS concentrations to rise. And due to another effect of alcohol, the intestine cannot be repaired during this. Wang et al., (2013) demonstrated that alcohol inhibits the transcription of bacterial proteins that metabolize long chain triglycerols to LCFAs, the major energy source for Lactobacillus. Lactobacillus produces compounds that inhibit the inflammation proliferating leaky gut as well as compounds necessary for tight junction formation; therefore without LCFAs, Lactobacillus is unable to reduce or repair leaky gut (Wang et al., 2013). In short: alcohol causes leaky gut with both direct pathways, such as the disruption of intestinal cell tight junctions, and indirect pathways, such as the positive feedback loop …show more content…
Alcohol’s fermented state disrupts the tight joints of the intestinal wall, allowing ligands to enter the portal vein that trigger the immune system to inflame the area, resulting in increased intestinal permeability and a positive feedback loop of inflammation that cannot be corrected by Lactobacillus due to the alcohol inhibiting the synthesis of LCFAs that Lactobacillus needs to function (Llorente and Schnabl, 2015; Wang et al., 2013). Alcohol also causes fat build-ups in the liver, commonly referred to as fatty