The gut mycobiome significantly affects host health and immunity. However, most studies have focused on symbiotic bacteria in the gut microbiome, whereas less attention has been given to symbiotic fungi. Although fungi constitute only 0.01%-0.1% of the gut microbiome, their larger size and unique immunoregulatory functions make them significant. Factors like diet, antimicrobials use, and age can disrupt the fungal community, leading to dysbiosis. Fungal-bacterial-host immune interactions are critical in maintaining gut homeostasis, with fungi playing a role in mediating immune responses such as Th17 cell activation. This review highlights methods for studying gut fungi, the composition and influencing factors of the gut mycobiome, and its potential in therapeutic interventions for intestinal and hepatic diseases. We aim to provide new insights into the underexplored role of gut fungi in human health.

The human gut harbors a complex and diverse microbiota essential for maintaining health. Diet is the most significant modifiable factor influencing gut microbiota composition and function, particularly through bioactive compounds like polyphenols, dietary fibers, and carotenoids found in vegetables, fruits, seafood, coffee, and green tea. These compounds regulate the gut microbiota by promoting beneficial bacteria and suppressing harmful ones, leading to the production of key microbiota-derived metabolites such as short-chain fatty acids, bile acid derivatives, and tryptophan metabolites. These metabolites are crucial for gut homeostasis, influencing gut barrier function, immune responses, energy metabolism, anti-inflammatory processes, lipid digestion, and modulation of gut inflammation. This review outlines the regulatory impact of typical bioactive compounds on the gut microbiota and explores the connection between specific microbiota-derived metabolites and overall health. We discuss how dietary interventions can affect disease development and progression through mechanisms involving these metabolites. We examine the roles of bioactive compounds and their metabolites in the prevention and treatment of diseases including inflammatory bowel disease, colorectal cancer, cardiovascular diseases, obesity, and type 2 diabetes mellitus. This study provides new insights into disease prevention and underscores the potential of dietary modulation of the gut microbiota as a strategy for improving health.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and shows high global incidence and mortality rates. The liver is an immune-tolerated organ with a specific immune microenvironment that causes traditional therapeutic approaches to HCC, such as chemotherapy, radiotherapy, and molecular targeted therapy, to have limited efficacy. The dramatic advances in immuno-oncology in the past few decades have modified the paradigm of cancer therapy, ushering in the era of immunotherapy. Currently, despite the rapid integration of cancer immunotherapy into clinical practice, some patients still show no response to treatment. Therefore, a rational approach is to target the tumor microenvironment when developing the next generation of immunotherapy. This review aims to provide insights into the hepatic immune microenvironment in HCC and summarize the mechanisms of action and clinical usage of immunotherapeutic options for HCC, including immune checkpoint blockade, adoptive therapy, cytokine therapy, vaccine therapy, and oncolytic virus-based therapy.

Gastric cancer (GC) is the leading cause of cancer-related death worldwide, and reducing its mortality has become an urgent public health issue. Gastric microecological dysbiosis (including bacteria, fungi, viruses, acid suppressants, antibiotics, and surgery) can lead to gastric immune dysfunction or result in a decrease in dominant bacteria and an increase in the number and virulence of pathogenic microorganisms, which in turn promotes development of GC. This review analyzes the relationship between gastric microecological dysbiosis and GC, elucidates dynamic alterations of the microbiota in Correa’s cascade, and identifies certain specific microorganisms as potential biomarkers of GC to aid in early screening and diagnosis. In addition, this paper presents the potential of gastric microbiota transplantation as a therapeutic target for gastric cancer, providing a new direction for future research in this field.

This review synthesizes recent research findings and proposes an integrated “microbiota–metabolite–immune–oncology” framework, highlighting how gut-derived metabolites regulate the dynamics of tumor immunity and informing the development of next-generation immunotherapies. Key metabolites—including short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine N-oxide (TMAO), indole-3-propionic acid (IPA), and urolithin A—exert bidirectional effects on antitumor immunity through multiple mechanisms. These include histone acetylation-driven epigenetic reprogramming, aryl hydrocarbon receptor (AhR)- and farnesoid X receptor (FXR)-mediated metabolic reprogramming, and direct regulation of immune effectors such as CD8 ⁺ T cells and myeloid-derived suppressor cells. Emerging evidence highlights specific roles of these metabolites within the tumor microenvironment (TME): microbial dysbiosis can amplify immunosuppressive circuits, whereas targeted enrichment of certain metabolites may enhance the efficacy of immune checkpoint blockade. Integrative multi-omics analyses have revealed the vascular remodeling effect of TMAO and the spatiotemporal heterogeneity of BAs, thereby connecting the gut-liver-tumor axis and achieving overall immune regulation. By mapping a precision-oriented metabolic roadmap, this review identifies underexplored therapeutic avenues—such as metabolite-targeted interventions and engineered probiotics—that, when combined with immune checkpoint inhibitors, may enable personalized, microbiome−based strategies with the potential to improve outcomes in cancer immunotherapy.

Introduction: Despite the established influence of gut bacteria, the role of the gut virome in modulating colorectal cancer (CRC) patient chemotherapy response remains poorly understood. In this study, we investigated the impact of antiviral (AV) drug-induced gut virome dysbiosis on the efficacy of 5-FU in CRC treatment.Methods: Using a subcutaneous CRC mouse model, we assessed tumor growth and immune responses following AV treatment, fecal microbiota transplantation (FMT), and 5-FU administration.Results: AV therapy reduced the abundance of gut DNA and RNA viruses, leading to accelerated tumor growth, shortened survival, and diminished chemotherapy efficacy. FMT restored the gut virome, improving tumor suppression and extending the survival of 5-FU-treated mice. Metagenomic sequencing revealed significant changes in virome composition, AV treatment expanded Kahnovirus, Petivirales, and Enterogokushovirus, whereas FMT enriched Peduovirus STYP1, Mahlunavirus rarus, and Jouyvirus ev207. AV treatment reduced the number of dendritic cells and CD8+ T cells in peripheral blood and tumor tissues, impairing antitumor immunity, FMT reversed these deficiencies. To further investigate the underlying mechanisms, we examined the TLR3-IRF3-IFN-β pathway, essential for recognizing viral RNA and triggering immune responses. AV treatment downregulated this pathway, impairing immune cell recruitment and reducing chemotherapy efficacy, while activation of TLR3 with Poly(I:C) restored pathway function and enhanced the effectiveness of 5-FU.Discussion: These findings suggest the importance of maintaining gut virome integrity or activating TLR3 as adjunct strategies to enhance chemotherapy outcomes in CRC patients.