Gut microbial dysbiosis: The hidden culprit behind Aplastic anaemia?

Aplastic anaemia (AA) is an autoimmune haematological disorder characterized by pancytopenia and hypocellular bone marrow. Several environmental factors are associated with the aetiology of this disorder. At present, haematopoietic stem cell transplantation (HCT) and immunosuppressive therapy (IST) are the only available therapies. The majority of patients do not respond to these therapies; responders even relapse in the future. That is why alternative supportive care or therapies are necessary. Emerging evidence suggests the potential role of gut microbiota (GM) dysbiosis in the pathogenesis of AA. There are reports of positive outcomes in haematopoiesis after treatment for an inflamed gut. Although patient-based studies are scarce, several altered gut bacterial species have been reported. A higher relative abundance of Proteobacteria and a lower abundance of Bacteroidetes have been noted in AA cases compared to the controls. Dysbiosis of GM has been shown to regulate the host immune system and the bone marrow microenvironment. Moreover, an altered microbiome has the potential to hamper haematopoietic events as well as the immune functions. Metabolites (Lipopolysaccharides) from an altered microbiota might upregulate proinflammatory cytokines such as TNF-α and IFN-γ. Such metabolites may also reach the bone marrow through the bloodstream and hamper haematopoiesis. Interestingly, environmental exposure to heavy metals, chemicals, pesticides, etc. has been reported to alter the gut epithelial integrity, leading to a “leaky gut”. A damaged epithelium is permeable to external antigens that ultimately cause proinflammatory reactions and autoimmunity. Thus, GM dysbiosis eventually may lead to a pathophysiology related to aplastic anaemia. Hence, microbiota-targeted therapies (probiotics, prebiotics, faecal microbiota transplantation, etc.) may soon aid in managing aplastic anaemia.