Network Analysis of Pathogenesis Markers in Murine Chagas Disease Under Antimicrobial Treatment

Chagas disease (CD), a disease affecting millions globally, remains shrouded in scientific uncertainty, particularly regarding the role of the intestinal microbiota in disease progression. This study investigates the effects of antibiotic-induced microbiota depletion on parasite burden, immune responses, and clinical outcomes in BALB/c mice infected with either the <i>Trypanosoma cruzi</i> Colombiana or CL Brener strains. Mice were treated with a broad-spectrum antibiotic cocktail before infection, and parasite burden was quantified via qPCR at 30 and 100 days post-infection (dpi). Immune responses were analyzed using flow cytometry and ELISA, while histopathology was conducted on cardiac and intestinal tissues. Antibiotic treatment uncovered strain-specific correlations, with Colombiana infections affecting <i>Bifidobacterium</i> populations and CL Brener infections linked to <i>Lactobacillus.</i> Microbiota depletion initially reduced parasite burden in the heart and intestine, but an increase was observed in the chronic phase, except in the CL Brener-infected gut, where an early burden spike was followed by a decline. Antibiotic-induced bacterial shifts, such as reductions in <i>Bacteroides</i> and <i>Bifidobacterium</i>, promoted a more pro-inflammatory immune profile. These findings highlight the importance of microbiota and strain-specific factors in CD and suggest further research into microbiota manipulation as a potential therapeutic strategy.