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. 2023 Aug 10;14:1174140. doi: 10.3389/fimmu.2023.1174140

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Copyright © 2023 Shukla, Rao, Meena, Giorgianni, Lee, Raju, Shashikanth, Shekhar, Beranova, Balazs, Tigyi, Gosain and Rao

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Graphic summary. 1) Radiation-induced Paneth cell dysfunction down-regulates α-defensin expression. 2) α-Defensin depletion leads to dysbiosis of gut microbiota, causing increased LPS production. 3) Radiation disrupts epithelial tight junctions leading to increased LPS translocation. 4) Increased LPS translocation results in endotoxemia. 5) Endotoxemia leads to systemic inflammation. 6) Human defensin-5 (HD-5) supplementation attenuates and mitigates radiation-induced microbiota dysbiosis, endotoxemia, and systemic inflammation.