GUT MICROBIOTA AND SYSTEMIC IMMUNITY: MECHANISMS LINKING MICROBIAL SIGNALS TO INFLAMMATION AND IMMUNOTHERAPY RESPONSE

Abstract

The gut microbiome is a complex microbial bionetwork that constantly modulates the immune system of the host. This interaction is responsible for controlling systemic inflammation and directing the course of immunity in various diseases. This review summarizes the present data on microbiome-immune system interactions, with a special emphasis on microbiome effects in inflammation and immunotherapy. Multiple molecular pathways enable the gut microbiome to influence host immune function. Gut microbial byproducts, including tryptophan derivatives, Short-Chain Fatty Acids, and bile acids, influence phagocytic cell development in addition to cytokine production. Structural components such as lipopolysaccharides activate pattern-recognition receptors and drive systemic inflammatory signaling. Dysbiosis reduces beneficial commensal taxa and increases microbial translocation. This disrupts intestinal barrier integrity and promotes chronic, low-grade inflammation linked to metabolic, autoimmune, and oncological conditions. Clinical evidence demonstrates that gut microbial composition significantly influences cancer immunotherapy end results. In melanoma, hepatocellular carcinoma, and non-small cell lung cancer, increased microbial heterogeneity and enrichment of specific taxa correlate with improved efficacy of Immune Checkpoint Inhibitors. Fecal Microbiota Transplantation studies provide causal evidence that microbiome composition can determine immunotherapy responsiveness. Specific microbial profiles also associate with immune-driven toxicities, such as checkpoint inhibitor-associated colitis. Dietary modification, probiotics, prebiotics, and synbiotics collectively represent potential interventions to reconstitute microbial homeostasis as well as improve immune outcomes. However, substantial challenges remain, including inter-individual variability, limited methodological standardization, and difficulty establishing causality in observational studies. Future research integrating multi-omics approaches may enable microbiome-based biomarkers and personalized immunotherapy strategies.