Modulating Cardiac-Gut Microbiome Interaction Post-Myocardial Infarction with Engineered Bacteria

Madaan, T.; Nieman, M.; Rakheja, T.; Siddiqui, N.; Gherardini, D.; Sertorio, M.; Kamble, N.; Thomas, S.; Hartman, A.; Koch, S.; Knipper, L.; Marino, V. A.; Sadayappan, S.; Lorenz, J. N.; Konhilas, J. P.; Kotagiri, N.

doi:10.1101/2025.07.10.664025

bioRxiv · 10.1101/2025.07.10.664025

Modulating Cardiac-Gut Microbiome Interaction Post-Myocardial Infarction with Engineered Bacteria

Madaan, T.·Nieman, M.·Rakheja, T.·Siddiqui, N.·Gherardini, D.·Sertorio, M.·Kamble, N.·Thomas, S.·Hartman, A.·Koch, S.·Knipper, L.·Marino, V. A.·Sadayappan, S.·Lorenz, J. N.·Konhilas, J. P.·Kotagiri, N.

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Abstract

The gut microbiome plays a critical role in the pathophysiology of acute myocardial infarction (MI). MI events significantly impact intestinal integrity which results in leakage of bacterial products into the systemic circulation. We demonstrate that MI not only compromises intestinal integrity, leading to systemic leakage of bacterial products like LPS, but also results in the translocation and colonization of live, intact gut bacteria in the MI heart - a novel aspect of the heart-gut axis. Our initial findings with natural murine gut microbiome were substantiated using orally administered E. coli Nissle 1917 (EcN), as a tracer bacterium. Furthermore, we engineered EcN to express the microbial anti-inflammatory molecule (MAM) derived from the probiotic Faecalibacterium prausnitzii. Treatment with this engineered strain, EcN-MAM, led to significantly improved survival and cardiac function in MI mice. This was attributed to enhanced gut barrier integrity, resulting in reduced systemic bacterial permeation and subsequent inflammation. These findings shed light on a previously unrecognized dimension of the heart-gut axis and highlight the potential of microbiome-based interventions in MI management.

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Madaan, T., Nieman, M., Rakheja, T., Siddiqui, N., Gherardini, D., Sertorio, M., Kamble, N., Thomas, S., Hartman, A., Koch, S., Knipper, L., Marino, V. A., Sadayappan, S., Lorenz, J. N., Konhilas, J. P., Kotagiri, N.. 2025-07-12. Modulating Cardiac-Gut Microbiome Interaction Post-Myocardial Infarction with Engineered Bacteria. https://doi.org/10.1101/2025.07.10.664025

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