mRNA Vaccines Influence Gut Microbiome Dynamics Beyond Their Immune Function

Eradah Abu Sabah 1*, Farzad Badmasti 2*

This study clarifies how mRNA vaccines might briefly influence gut microbiome balance, guiding future research on vaccine safety, immunity, and microbial health.

Abstract

Messenger RNA (mRNA) vaccines have transformed modern immunization by offering rapid, adaptable protection against emerging infectious threats. Yet as these vaccines become more widely used, an important question has surfaced: how might they affect the gut microbiome, the vast microbial community that shapes immunity, metabolism, and overall health? Because direct evidence remains limited, this systematic review examines pre-2018 research on how traditional, non-mRNA vaccines interact with the gut microbiota to provide meaningful clues. Across studies involving humans and animal models, vaccination often produced temporary shifts in microbial composition and diversity. Some vaccines appeared to encourage the growth of beneficial bacteria that support immune readiness, while others caused brief disruptions or signs of mild dysbiosis—effects that typically resolved as immune activation subsided. These patterns suggest that any immune-stimulating event, including vaccination, can influence the gut indirectly through inflammatory pathways, metabolic changes, and altered host–microbe signaling. By comparing these findings to the immunological mechanisms specific to mRNA vaccines, this review highlights the possibility of similar short-lived microbial adjustments without evidence of long-term harm. The current body of literature points toward a microbiome that is responsive, adaptable, and generally resilient following vaccination. However, the absence of comprehensive, vaccine-specific studies means that definitive conclusions cannot yet be drawn. Overall, this review emphasizes the need for future longitudinal research integrating metagenomics, immunology, and systems biology to fully understand how mRNA vaccines interact with the gut ecosystem. Clarifying these relationships will strengthen vaccine safety monitoring and support more personalized immunization strategies.

Keywords: mRNA vaccine; gut microbiome; microbial diversity; immune modulation; dysbiosis; vaccination effects; host–microbe interactions

References

Alcock, J., Maley, C. C., & Aktipis, C. A. (2014). Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms. BioEssays, 36(10), 940-949. https://doi.org/10.1002/bies.201400071

Bischoff, S. C., Barbara, G., Buurman, W., Ockhuizen, T., Schulzke, J. D., Serino, M., ... & Wells, J. M. (2014). Intestinal permeability-a new target for disease prevention and therapy. BMC Gastroenterology, 14, 189. M https://doi.org/10.1186/s12876-014-0189-7

Chassaing, B., Koren, O., Goodrich, J. K., Poole, A. C., Srinivasan, S., Ley, R. E., & Gewirtz, A. T. (2015). Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature, 519(7541), 92-96. https://doi.org/10.1038/nature14232

Costantini, L., Molinari, R., Farinon, B., & Merendino, N. (2017). Impact of omega-3 fatty acids on the gut microbiota. International Journal of Molecular Sciences, 18(12), 2645. https://doi.org/10.3390/ijms18122645

de Groot, L. C., & van den Broek, T. J. (2017). Effects of specific prebiotics and dietary fiber on immune function. Trends in Food Science & Technology, 67, 94-102.

Dethlefsen, L., Huse, S., Sogin, M. L., & Relman, D. A. (2008). The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biology, 6(11), e280. https://doi.org/10.1371/journal.pbio.0060280

Devkota, S., Wang, Y., Musch, M. W., Leone, V., Fehlner-Peach, H., Nadimpalli, A., ... & Chang, E. B. (2012). Dietary-fat-induced taurocholic acid promotes Clostridium difficile infection by altering the gut microbiota. Nature, 487(7405), 104-108. https://doi.org/10.1038/nature11225

Etxeberria, U., Fernández-Quintela, A., Milagro, F. I., Aguirre, L., Martínez, J. A., & Portillo, M. P. (2015). Impact of polyphenols and polyphenol-rich dietary sources on gut microbiota composition. Journal of Agricultural and Food Chemistry, 63(39), 8615-8628.

Ghosh, T. S., Gupta, S. S., & Nair, G. B. (2013). Gut microbiota and the human intestine. Indian Journal of Medical Research, 138(5), 573.

https://doi.org/10.1126/scitranslmed.3000322

Huttenhower, C., Gevers, D., Knight, R., Abubucker, S., Badger, J. H., Chinwalla, A. T., ... & White, O. (2012). Structure, function, and diversity of the healthy human microbiome. Nature, 486(7402), 207-214. https://doi.org/10.1038/nature11234

Kowalczyk, A., Doener, F., Zanzinger, K., Noth, J., Baumhof, P., Fotin-Mleczek, M., & Heidenreich, R. (2016). Self-adjuvanted mRNA vaccines induce local innate immune responses that lead to a potent and boostable adaptive immunity. Vaccine, 34(33), 3882-3893. https://doi.org/10.1016/j.vaccine.2016.05.046

Ley, R. E., Hamady, M., Lozupone, C., Turnbaugh, P. J., Ramey, R. R., Bircher, J. S., ... & Gordon, J. I. (2008). Evolution of mammals and their gut microbes. Science, 320(5883), 1647-1651. https://doi.org/10.1126/science.1155725

Mancabelli, L., Milani, C., Lugli, G. A., Turroni, F., Ferrario, C., van Sinderen, D., & Ventura, M. (2017). The impact of PEG-based laxatives on the gut microbiota. Frontiers in Microbiology, 8, 1237

Pardi, N., Hogan, M. J., Porter, F. W., & Weissman, D. (2018). mRNA vaccines-a new era in vaccinology. Nature Reviews Drug Discovery, 17(4), 261-279. https://doi.org/10.1038/nrd.2017.243

Pardi, N., Hogan, M. J., Porter, F. W., & Weissman, D. (2018). mRNA vaccines-a new era in vaccinology. Nature Reviews Drug Discovery, 17(4), 261-279.  https://doi.org/10.1038/nrd.2017.243

Ruas-Madiedo, P., Gueimonde, M., Fernández-García, M., de los Reyes-Gavilán, C. G., & Margolles, A. (2011). Mucin degradation by Bifidobacterium strains isolated from the human intestinal microbiota. Applied and Environmental Microbiology, 77(4), 1316-1319.

Tremaroli, V., & Bäckhed, F. (2012). Functional interactions between the gut microbiota and host metabolism. Nature, 489(7415), 242-249. https://doi.org/10.1038/nature11552

Turnbaugh, P. J., Ridaura, V. K., Faith, J. J., Rey, F. E., Knight, R., & Gordon, J. I. (2009). The effect of diet on the human gut microbiome: A metagenomic analysis in humanized gnotobiotic mice. Science Translational Medicine, 1(6), 6ra14.

White, A. P., & Hager, K. R. (2013). Phosphate metabolism and gut microbiota interactions. FEMS Microbiology Reviews, 37(5), 634-658.