Introduction: During the last two decades, appreciation of the complementary roles played by host genetics and the gut microbiota in disease pathogenesis has transformed our understanding of diseases. Among such conditions, inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is considered a paradigm for chronic inflammation and gastrointestinal pathology mediated by complex gene–environment interactions. IBD is a multifactorial disease in which both genetic susceptibility and gut microbiota composition have been independently implicated as risk factors. However, the detailed mechanisms through which host genetics and microbiota interact to influence IBD severity remain incompletely understood. This research therefore aims to investigate the host–microbiota interactions that contribute synergistically to IBD development and severity, providing insights into how these factors influence disease outcomes. Method: This review was conducted by analyzing research from databases including PubMed and Scopus, focusing on genetic and microbiota factors associated with IBD, encompassing both CD and UC. Studies published between 2010 and 2025 that investigated the interactions between host genetics and gut microbiota in disease development were included. Results: Our findings reveal that IBD is characterized by profound host–microbiome disturbances shaped by key genetic pathways. Patients consistently showed marked depletion of SCFA-producing Firmicutes, including Faecalibacterium prausnitzii and Roseburia, along with reduced abundance of major Bacteroidetes taxa. These shifts were accompanied by a notable expansion of Proteobacteria, particularly Enterobacteriaceae, and an accumulation of pro-inflammatory metabolites, including succinate and hydrogen sulfide, indicating a metabolically inflammatory microbial profile. Genetic variants across multiple functional groups—including innate immune sensing (NOD2, TLRs, CLEC7A), autophagy machinery (ATG16L1, ATG5, IRGM, CARD9), epithelial barrier and glycosylation pathways (FUT2, MUC2, MAN2A1), inflammatory signaling (IL23R, TNFSF15, HLA-DQA1), and metabolite transport (SLC22A5)—were strongly associated with these microbial shifts. These combined alterations weaken epithelial integrity by impairing tight junctions and mucosal barrier repair, processes strongly influenced by genes such as NOD2, ATG16L1, and IL23R. Reduced SCFA-producing bacteria further compromise epithelial energy supply and anti-inflammatory signaling, while risk variants in immune-regulatory genes trigger exaggerated microbial sensing and overactivation of inflammatory pathways (e.g., NF-κB and Th17). The expansion of Proteobacteria and accumulation of pro-inflammatory metabolites amplify this cycle of dysbiosis and immune dysregulation, creating a self-reinforcing gene–microbiome loop that drives mucosal injury and contributes directly to IBD pathogenesis. Conclusion: Genetic variation in the host is a major determinant of gut microbiota composition in IBD and significantly influences disease severity and progression. Elucidating these host–microbiota interactions may guide personalized therapeutic strategies, including microbiota-targeting interventions, dietary modulation, and precision medicine. Integrating genetic profiling with microbiome analysis could enable predictive biomarkers for selecting optimal treatments, ultimately improving disease management and patient outcomes. Keywords: • Inflammatory bowel disease (IBD) • Gut microbiota • Host genetics • Gene–microbiome interactions