Delta State University Abraka, Nigeria.
ABSTRACT Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by chronic hemolysis, recurrent vaso-occlusive crises, endothelial dysfunction, and persistent systemic inflammation. Although advances in newborn screening, hydroxyurea therapy, chronic transfusion protocols, and more recently gene-based therapies have improved patient survival, chronic inflammatory complications continue to contribute substantially to morbidity and mortality. In recent years, the gut microbiome has emerged as a critical regulator of immune homeostasis, metabolism, vascular integrity, and inflammatory signaling. Alterations in gut microbial composition, collectively referred to as gut microbiome dysbiosis, have been implicated in numerous chronic inflammatory disorders, including inflammatory bowel disease, obesity, diabetes mellitus, cardiovascular disease, and autoimmune conditions. Growing evidence suggests that similar alterations occur in patients with SCD, where repeated ischemia-reperfusion injury, intestinal hypoxia, frequent antibiotic exposure, altered dietary patterns, and compromised epithelial barrier integrity collectively disrupt the normal intestinal microbial ecosystem. Gut microbiome dysbiosis may contribute directly to chronic inflammation through increased intestinal permeability, translocation of microbial products, activation of innate immune receptors, and excessive production of pro-inflammatory cytokines. These mechanisms promote neutrophil activation, endothelial dysfunction, platelet aggregation, and enhanced adhesion of sickled erythrocytes, thereby exacerbating vaso-occlusive events and multiple organ damage. Several studies have demonstrated significant reductions in beneficial commensal bacteria together with enrichment of pathogenic taxa in individuals with SCD, suggesting that microbial imbalance may represent both a biomarker of disease severity and a potential therapeutic target. This review critically examines current knowledge regarding the composition of the gut microbiome in SCD, the mechanisms linking intestinal dysbiosis with systemic inflammation, and the relationship between microbial alterations and clinical manifestations of disease severity. Emerging microbiome-directed interventions, including probiotics, prebiotics, dietary modulation, and fecal microbiota transplantation, are also discussed. Finally, current research limitations and future directions for microbiome-based precision medicine in SCD are highlighted.
