Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of dysregulated lipid and glucose metabolism, which is often associated with obesity, dyslipidemia and insulin resistance. In view of the high morbidity and health risks of NAFLD, the lack of effective cure has drawn great attention. In recent years, a line of evidence has suggested a close linkage between the intestine and liver diseases such as NAFLD. We summarized the composition and characteristics of intestinal microbes and reviewed molecular insights into the intestinal microbiome in development and progression of NAFLD. Intestinal microbes mainly include bacteria, archaea, viruses and fungi, and the crosstalk between non-bacterial intestinal microbes and human liver diseases should be paid more attention. Intestinal microbiota imbalance may not only increase the intestinal permeability to gut microbes but also lead to liver exposure to harmful substances that promote hepatic lipogenesis and fibrosis. Furthermore, we focused on reviewing the latest “gut–liver axis”-targeting treatment, including the application of antibiotics, probiotics, prebiotics, synbiotics, farnesoid X receptor agonists, bile acid sequestrants, gut-derived hormones, adsorbents and fecal microbiota transplantation for NAFLD. In this review, we also discussed the potential mechanisms of “gut–liver axis” manipulation and efficacy of these therapeutic strategies for NAFLD treatment.

Gut microbiota plays a critical role in the maintenance of host health. As a low-cost and genetically tractable vertebrate model, zebrafish have been widely used for biological research. Zebrafish and humans share some similarities in intestinal physiology and function, and this allows zebrafish to be a surrogate model for investigating the crosstalk between the gut microbiota and host. Especially, zebrafish have features such as high fecundity, external fertilization, and early optical transparency. These enable the researchers to employ the fish to address questions not easily addressed in other animal models. In this review, we described the intestine structure of zebrafish. Also, we summarized the methods of generating a gnotobiotic zebrafish model, the factors affecting its intestinal flora, and the study progress of gut microbiota functions in zebrafish. Finally, we discussed the limitations and challenges of the zebrafish model for gut microbiota studies. In summary, this review established that zebrafish is an attractive research tool to understand mechanistic insights into host-microbe interaction.

Ulcerative colitis (UC) has been confirmed as a disease with a high incidence and low cure rate worldwide. In severe cases, UC can develop into colon cancer. Modern research has confirmed that berberine (BBR) can treat UC by inhibiting the expressions of inflammatory factors. However, the contribution of gut microbiota and flora metabolites in treating UC with BBR remains unclear. In this study, the ameliorative effects of BBR on gut microbiota dysbiosis and flora metabolites were investigated in a dextran sodium sulfate (DSS)-induced UC rodent model. We found that BBR significantly improved the pathological phenotype, attenuated intestinal barrier disruption, and mitigated colonic inflammation in DSS mice. By 16 S rDNA sequencing, BBR alleviated gut microbiota dysbiosis in UC mice. Moreover, the gut microbiota depletion experiment confirmed that the therapeutic effect of BBR was inextricably correlated with the gut microbiota. Besides, the flora metabolites (e.g., short-chain fatty acids, bile acids, and 5-hydroxytryptamine) were studied using HPLC-MS. The results suggested that BBR ameliorated the bile acid imbalance induced by DSS in the liver and gut. Furthermore, BBR treatment repaired gut barrier damage. The above results revealed that BBR alleviated DSS-induced UC in mice by restoring the disturbed gut microbiota, elevating unconjugated and secondary bile acids in the gastrointestinal tract, and activating the FXR and TGR5 signal pathway. This study provides novel insights into the mechanism of BBR in treating UC.