Gut microbial dysbiosis in Gaucher disease: implications for associated complications

The human gut microbiome is a highly dynamic and exceptionally diverse microbial ecosystem. Gut dysbiosis, or an imbalance in gut microbiota, can lead to various metabolic conditions associated with immune activation and systemic inflammation. Gaucher disease (GD) is a rare lysosomal disorder caused by variations in the GBA1 (Glucosylceramidase Beta 1) gene, leading to the accumulation of glucocerebrosides in lysosomes, predominantly in macrophages. This leads to multi-organ complications in patients, such as hepatosplenomegaly, hematological and skeletal abnormalities. GBA1 variants also predispose individuals to neurodegenerative disorders such as Parkinson's disease (PD). Emerging preclinical evidence suggests that gut dysbiosis may contribute to the pathophysiology of GD and related complications, although causal relationships have not been established. Recent studies have reported gut microbial alterations in preclinical models harboring GBA1 variants, descriptively linking dysbiosis with chronic immune activation and PD-related phenotypes. Additional research is warranted to define the role of gut dysbiosis in the pathogenesis of GD and to explore potential adjunctive strategies in a hypothesis-generating context. This review summarizes current evidence regarding gut dysbiosis in GD and discusses its conceptual relevance to immunological, metabolic, neurological, and skeletal manifestations in a hypothesis-generating framework. Probiotics, prebiotics, synbiotics, dietary supplements, and lifestyle modifications are discussed as exploratory adjunctive approaches that warrant further investigation in parallel with established GD therapies.