Host metabolic reprogramming ameliorates disease severity and colitis during <i>Clostridioides difficile</i>infection

Abstract Clostridioides difficile is an anaerobic, opportunistic bacterium that can cause severe infections in the gastrointestinal tract upon disruption of gut microbiome. C. infection (CDI) affects 450,000 people yearly only U.S. The high recurrence rates associated to antibiotic regimen, current standard care, highlight need investigate novel antimicrobial free therapeutic approaches for treatment CDI. Here, we have conducted a global transcriptomics analysis and metabolic computational modeling, using our developed M 2pipeline, vivo murine 10-day time course study CDI identify host mechanisms with potential. Our has reported biphasic modulation colonic metabolism, characterized by increased glycolysis during induction effector responses, while mitochondrial metabolism favored recovery phase infection, when regulatory healing processes are predominant. Inhibition through administration 2-Deoxy-D-glucose (2-DG) ameliorates diseases severity, protects from mortality, reduces colitis mouse model In vitro 2-DG, inhibitor glycolysis, T-84 cells exposed toxins A B epithelial barrier integrity decreases secretion inflammatory mediators. conclusion, immunometabolic reprogramming represents promising antimicrobial-free approach Supported grant DTRA (HDTRA1-20-1-0021)