Early-life exposures to specific commensal microbes prevent type 1 diabetes.

Green, J.; Deschaine, J.; Lubin, J.-B.; Flores, J. N.; Maddux, S.; Duranova, T.; Grimes, L.; Planet, P. J.; Eisenlohr, L. C.; Silverman, M. A.

doi:10.1101/2024.02.15.580579

bioRxiv · 10.1101/2024.02.15.580579

Early-life exposures to specific commensal microbes prevent type 1 diabetes.

Green, J.·Deschaine, J.·Lubin, J.-B.·Flores, J. N.·Maddux, S.·Duranova, T.·Grimes, L.·Planet, P. J.·Eisenlohr, L. C.·Silverman, M. A.

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Abstract

Early-life disruptions of the gut microbiome have long-lasting impacts on the risk of developing autoimmune diseases. How the composition of the early-life microbiota contributes to autoimmunity and whether manipulating it can prove therapeutically beneficial remains largely unexplored. Here we demonstrate that a simple consortium of nine early-life commensal bacteria (PedsCom) prevents type 1 diabetes (T1D) in diabetes-susceptible NOD mice. Remarkably, we find that this protection is completely dependent upon early-life colonization. During this critical time window of early-life colonization and immune development, specific microbes unexpectedly translocate from the gut to peripheral tissues and induce the tolerogenic responses required for T1D protection. These findings highlight how the timing and localization of microbial interactions during a pivotal stage of immune development contribute to protection from T1D. Altogether, these findings suggest an opportunity to develop microbial therapies for human infants to prevent autoimmune diseases. One sentence summaryA defined consortium of early-life microbes shapes immune development and prevents type 1 diabetes.

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Green, J., Deschaine, J., Lubin, J.-B., Flores, J. N., Maddux, S., Duranova, T., Grimes, L., Planet, P. J., Eisenlohr, L. C., Silverman, M. A.. 2024-02-20. Early-life exposures to specific commensal microbes prevent type 1 diabetes.. https://doi.org/10.1101/2024.02.15.580579

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