FIGURE 2.

Probiotics’ effect on the gut-microbiota-liver-brain axis in ALD. Probiotics exert their actions at different levels of the gut-microbiota-liver-brain axis, acting directly on each of these organs and indirectly due to the axis component's interplay. (A) At the intestinal level, probiotics improve digestion and tight junction’s expression and are a protective factor for the crypts and mucous layer. (B) The change enhances the effects that probiotics produce in the microbiota, restoring it and decreasing dysbiosis triggered by alcohol abuse, which will lead to a decrease in harmful bacteria and an increase in beneficial ones, therefore reducing the high permeability of the gut and the translocation of PAMPs to the liver. (C) Probiotics’ effect in the brain causes a decrease in proinflammatory cytokines at the systemic level; consequently, the system and neuroinflammation are attenuated by a probiotic-based therapy. Inflammation control is one of the mechanisms behind controlling alcohol consumption and psychological symptoms, such as anxiety and depression. Furthermore, the control of high permeability and the translocation of substances contributes to controlling the disruption of the blood-brain barrier and neuroinflammation. Finally, FGF21 has an important effect on the brain since it produces dopamine transporter transcription in the nucleus accumbens, allowing less dopamine to access the postsynaptic receptor. (D) Probiotics have demonstrated multiple benefits at the liver level since the decrease of steatosis to encephalopathy and cirrhosis. These liver effects are explained by the decrease of PAMPs in the systemic circulation, especially LPS, that induce the normalization of the inflammatory processes that are associated, among others, with the TLR4 pathway. Consequently, the adverse effects of alcohol on the liver are decreased; less activation of Küpffer cells, decreased liver enzymes, proinflammatory cytokines, and less fibrosis. Some probiotics cause increased formation of FGF21 in the liver, which has effects on the brain. ALD: Alcoholic liver disease; SCFA: Short-chain fatty acids; PAMPs: Pathogen-associated molecular patterns; BBB: Blood-brain barrier; TLR4: Toll-like receptor 4; FGF21: fibroblast activation protein 21.