The “Immune Rebellion” from the Intestines to the Liver: A Vicious Cycle That Causes the Liver to Collapse

The gut immune microenvironment and the liver engage in intricate information exchange via the gut-liver axis. The disruption of these interactions plays a pivotal role in the formation and exacerbation of pathological damage to the liver. The gut immune microenvironment is not an independent layer of the gut barrier; rather, it permeates and regulates all other barrier functions, serving as the core coordinator. Disruption of the immune microenvironment in the gut-liver axis drives progression across the full disease spectrum-from steatosis to hepatitis, fibrosis, and even liver cancer-through the continuous influx of immune-stimulatory signals that overwhelm the liver's intrinsic immune regulatory mechanisms. Dysfunction of innate immunity components, amplification of inflammatory factors and key cellular signaling pathways, activation of adaptive immune T cells, and systemic effects mediated by liver-derived inflammatory factors collectively form a disordered immune microenvironment. This damages the intestinal barrier and exacerbates liver disease via the gut-liver axis, leading to further intestinal injury, thus establishing a self-reinforcing vicious cycle. Current therapeutic strategies based on modulating the gut-liver axis microenvironment remain limited, yet studies have demonstrated that suppressing gut immune cells, cytokines, and signaling pathways can help delay liver disease progression. Hopefully, future combined, precise, and cutting-edge gut immunotherapies will provide more effective strategies for liver disease treatment.