Gut Microbiota Modulation in Leptospirosis: Exploring Pathogenic Mechanisms and Novel Therapies

Leptospirosis, an emerging global zoonotic disease caused by Leptospira species. A wide range of clinical symptoms are present in this condition, from a low-grade fever to potentially fatal side effects like Weil's disease and pulmonary hemorrhage syndrome. The pathophysiology remains incompletely understood despite being a disease of epidemic proportions, particularly in tropical regions. Recent developments have indicated the gut microbiota to be a potent modifier of systemic immunity and its potential to modulate disease severity in infectious diseases. The review discusses how the gut microbiota modulates the pathogenesis of leptospirosis through dysbiosis, leading to immune dysregulation and systemic inflammation while causing localized damage to specific organs. Related bacterial infection research indicates that disruptions in gut microbiota worsen immune system imbalances and cytokine storms while intensifying multi-organ failure in severe leptospirosis cases. Microbiota-directed therapeutic approaches including probiotics, prebiotics, fecal microbiota transplantation and dietary modifications may decrease disease severity and improve clinical outcomes. There are several knowledge gaps in leptospirosis research that require comprehensive microbiota profiles, mechanisms of action and clinical trials to address and evaluate these therapeutic approaches. This review emphasizes that combining microbiota approaches with leptospirosis research will provide a novel, and potentially fruitful, direction for therapeutic development and address the acute need for new therapeutic against the neglected tropical disease.