The interaction between IL-17 and gut microbiota contributes to cholestatic liver disease in children

The pathogenesis of cholestatic liver disease (CLD) is unknown, but the influence of gut microbiota and inflammation cannot be ignored. In this study, we attempted to provide theoretical insights for the diagnosis and treatment of CLD in children by analysing the association between gut microbiota, IL-17 levels and clinical characteristics. This research involved 21 children diagnosed with CLD and 11 healthy controls. Blood and faecal samples were collected from these participants. Blood samples underwent analysis for clinical indicators and IL-17 concentrations. Gut microbiota was examined through 16S rRNA gene sequencing for identification and functional prediction. A positive correlation between IL-17 levels and clinical parameters (total bile acids, alanine aminotransferase, aspartate aminotransferase and triglycerides) in children with CLD was observed. Notably, children with CLD exhibited reduced diversity and disturbances in gut microbiota, highlighted by a severe decrease of Bacteroidota (genus Bacteroides). Moreover, increased relative abundance of secondary bile acid-promoting (e.g. Clostridium, Enterococcus and Bifidobacterium) and deleterious (e.g. Escherichia-Shigella and Streptococcus) flora in the intestinal flora of children with CLD was positively correlated with IL-17, leading to increased inflammation and CLD aggravation. Functional predictions of gut microbiota revealed higher concentrations of l-asparagine transporter, ABC-type polar amino acid transport system and glycolysis II (from fructose 6-phosphate) functions, while the function of the Na⁺-driven multidrug efflux pump was decreased. In conclusion, children suffering from CLD exhibit significant gut microbiota disturbances, particularly a severe decrease in Bacteroidota (genus Bacteroides). Dysbiosis of the gut microbiota and elevated levels of IL-17 mutually reinforce each other, together mediating the onset and progression of CLD.