The human gut contains a large number of microorganisms, and a healthy adult has about 1014 bacteria, 10 times the number of human cells, which are vital to human nutrition and metabolism as well as life and health [9] . According to the results of 16S rRNA sequence analysis, more than 1000 species of microorganisms routinely survive in the intestine, most of which belong to the phylum Bacteroides and Thick-walled Bacteroides [10] . These florae form a microecological balance system in the gastrointestinal tract of a healthy human body. When the balance of the number or types of flora is disrupted, resulting in dysbiosis, damage to intestinal mucosal cells and destruction of the intestinal barrier, it will lead to inflammatory diseases of the intestine itself, as well as diseases of other sites, such as hepatitis, pneumonia, cardiovascular disease, obesity, diabetes, tumors, and autism, depression, etc [11] .

The intestine and the liver are closely linked in both directions through the bile duct, portal vein and the body circulation, the “intestine-liver axis”. The liver communicates with the intestine by releasing bile acids and many biologically active mediators into the biliary tract and the body circulation. In the intestine, hosts and microorganisms metabolize endogenous (bile acids and amino acids) and exogenous (from dietary and environmental exposure) substrates, the products of which are transported to the liver via the portal vein and affect liver function. When the intestinal flora is dysregulated, the barrier function is impaired and the permeability of the intestinal mucosa increases, triggering the colonization and invasion of other potential pathogens (including conditionally pathogenic bacteria) in the intestine with bacterial translocation and accumulation of lipopolysaccharide (LPS), causes the development of liver disease. The intestinal-liver axis has implications for the pathogenesis of many chronic liver diseases, including chronic hepatitis B (CHB), chronic hepatitis C (CHC), alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC).

Immune checkpoint inhibitors (ICI) have made revolutionary advances in recent years as a novel and effective therapeutic approach to tumor immunotherapy, activating T cells and killing tumor cells through an active immune approach. (CTLA-4) and programmed cell death 1 (PD-1) and its ligand programmed death receptor ligand-1 (PD-1) [12] . Scientists have explored the relationship between intestinal flora and immune checkpoint inhibitors and found that intestinal flora can influence antitumor immunotherapy and predict the efficacy of immunotherapy.

Multiple studies show that enhancement of endogenous T-cell function by CTLA-4 blockade prolongs survival in patients with advanced metastatic melanoma [13] , Experiments with sterile or antibiotic (ATB) treated mice reveal that the antitumor activity of ICI requires the presence of intestinal microorganisms, that CTLA-4 antibody efficacy is compromised by the lack of intestinal commensal flora, and that Bacteroides phylum such as Bacteroides fragilis (Bf) and Burkholderia cepacia (Bc) can enhance interleukin 12 (IL-12)-dependent Th1 immune response and promote the maturation of dendritic cells (DC) in tumors, contributing to tumor control [14] . Another study found that CTLA-4 expression on breast cancer cells was functional and inhibited the maturation and function of DCs, and that CTLA-4 blockade not only restored the antigen-presenting function of DCs and T cell activation, but also inhibited the biological activity of the breast cancer cells themselves [15] .

Excellent results have also been achieved with immune checkpoint inhibitors (ICI) targeting the intestinal flora affecting the PD-1/PD-L1 axis. Lisa [16] et al. performed a bird shot macrogenomics-based microbiome analysis of advanced non-small cell lung cancer (NSCLC) patients treated with PD-1 blockade and showed that the relative abundance of the fecal mucinophilic Akkermans (Akk) was significantly associated with the efficacy of ICI treatment and confirmed that ATB use was associated with poor clinical outcomes [17] . In addition to consuming favorable genera (e.g., rumen cocci) [18] , it also biases the composition of the gut microbiome toward harmful bacteria (e.g., E. coli and Clostridium borreliae) [19] . By integrating three DNA sequence-based bacterial identification methods, including 16S ribosomal RNA gene sequencing, macrogenomic birdshot sequencing, and quantitative polymerase chain reaction of selected bacteria, Vyara et al. [20] scientists found that the commensal microbiome may have a mechanistic impact on antitumor immunity, and that beneficial species such as Bifidobacterium longum, Corynebacterium aerogenes, and Enterococcus faecalis are enriched in responding patients, and that fecal transplants from responders may improve tumor control, enhance T-cell responses, and improve the efficacy of PD-1 blockers. Routy et al. [21] Study of the efficacy of “fecal microbiota transplantation” or oral supplementation with the mucormycete Acinetobacter in restoring the efficacy of PD-1 blockade in a mouse epithelial tumor model with anti-pd-1 agents, where primary resistance to ICI can be attributed to an abnormal gut microbiome composition, was restored in an interleukin 12-dependent manner by increasing the recruitment of CCR9 + CXCR3 + CD4 + T lymphocytes to the tumor bed of mice.