About this Research Topic

Background

The Gut-Liver Axis describes a bidirectional interaction between the gut comprehending its mi-crobiome and the liver, in which gut-derived molecules and/or by-products are transported to the hepatocytes through the portal vein and the liver responds to the gut through the biliary system. Intestinal ecological dysbiosis refers to alterations in the intestinal flora characterized by changes in the intestinal bacterial taxa, and bacterial overgrowth itself may lead to impaired small intesti-nal motility. The integrity of this intestinal mucosal barrier and the physiological composition of the intestinal microbiome is essential for maintaining homeostasis of the gut-liver axis and its al-terations may impact on several liver diseases, such as NAFLD, liver cirrhosis and hepatocarcino-ma. Last but not the least, intestinal dysbiosis has a key role in modulating the hepatotoxicity (DILI) of clinically relevant drugs through various mechanisms that include changes in absorption, metabolism and effects on drug-drug interactions.

With this research topic we aim to gather new pieces of evidence on the potential mechanisms ex-plaining the connection between gut flora dysbiosis and liver damage:
1. The impairment of hepatocyte survival by toxic compounds generated by intestinal bacteria
2. The triggering of immune/inflammatory processes by toxic compounds generated by dysbiotic bacteria in the gut and transported to the liver
3. The genotoxicity on liver cells of gut bacterial mediators
4. The epigenetic modifications in the hepatocytes induced by intestinal bacteria
5. The impairment of the enterohepatic circulation of bile acids
6. The connection between microbiota-induced NAFLD/NASH and the risk of DILI
7. The conversion of orally-given drugs into toxic metabolites through bacterial metabolism taking place in the gut lumen
8. The disruption of the integrity of the epithelial intestinal barrier with the consequent bacte-rial translocation through a direct action of drugs on the intestinal mucosa
9. The modulation by the gut microbiota of the rewarding potential of hepatotoxic drugs of abuse leading to an increase in craving for these substances and ultimately in their intake and liver toxicity
10. The hypothesis that strategies aiming to modify the composition of gut microbiota with probiotics/prebiotics/symbiotics could ameliorate or prevent liver diseases.

In this Research Topic, we welcome both original articles and reviews on the following subtopics:
1. Intestinal microbiota and NAFLD
2. Intestinal microbiota and liver cirrhosis
3. Intestinal microbiota and hepatocarcinoma
4. Intestinal microbiota and DILI
5. Intestinal microbiota and primary biliary cholangitis
6. Intestinal microbiota and primary sclerosing cholangitis
7. Intestinal dysbiosis and liver damage in drug addiction
8. Impact of intestinal hormones on the microbiota
9. Role of probiotics in the treatment of liver disorders and DILI.

Keywords: drug-induced liver damage, hepatotoxicity, microbiota, pharmacokinetics, metagenomics, transcriptomics, proteomics, probiotics, prebiotics, symbiotics

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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