Fig. 9

Schematic presentation of gut microbiota-derived tryptophan metabolites and AhR/Nrf2 signaling in MCT-induced liver injury. Gut microbiota-derived tryptophan metabolites, such as IAAld and IAA, could activate AhR and facilitate the nuclear translocation and activation of Nrf2 in healthy conditions, which play a role in relieving the oxidative stress injury and maintaining liver homeostasis. MCT-associated dysbiosis with decreased tryptophan-metabolizing bacteria lead to deficiency of indoles derivatives in the gut. And as a result, the AhR/Nrf2 signaling to be silenced and the liver oxidative injury to be unrestrained, thereby expedites the progress of MCT-induced HSOS. AhR, aryl-hydrocarbon receptor; Nrf2, nuclear factor E2-related factor 2; IAAld, Indole-3-Acetaldehyde; IAA, Indole Acetic Acid; GCLC, glutamate-cysteine ligase catalytic subunit; GCLM, glutamate-cysteine ligase modifier subunit; NQO-1, NAD(P)H dehydrogenase quinone 1; HSP90, heat shock protein-90; SRC, steroid receptor co-activating factor; XAP2, X-associated protein-2; ARNT, aryl hydrocarbon receptor nuclear translocator; ARE, antioxidant responsive element