Gut Microbiota-Derived <span style="font-variant: small-caps">l</span>-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury
Radiation-induced cardiopulmonary injuries are the most common and intractable side effects that are entwined with radiotherapy for thorax cancers. However, the therapeutic options for such complications have yielded disappointing results in clinical applications. Here, we reported that gut microbio...
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| Autores principales: | , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/58fe2839ffec4f54b546f6116e7a6233 |
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| Sumario: | Radiation-induced cardiopulmonary injuries are the most common and intractable side effects that are entwined with radiotherapy for thorax cancers. However, the therapeutic options for such complications have yielded disappointing results in clinical applications. Here, we reported that gut microbiota-derived <span style="font-variant: small-caps;">l-</span>Histidine and its secondary metabolite imidazole propionate (ImP) fought against radiation-induced cardiopulmonary injury in an entiric flora-dependent manner in mouse models. Local chest irradiation decreased the level of <span style="font-variant: small-caps;">l</span>-Histidine in fecal pellets, which was increased following fecal microbiota transplantation. <span style="font-variant: small-caps;">l</span>-Histidine replenishment via an oral route retarded the pathological process of lung and heart tissues and improved lung respiratory and heart systolic function following radiation exposure. <span style="font-variant: small-caps;">l</span>-Histidine preserved the gut bacterial taxonomic proportions shifted by total chest irradiation but failed to perform radioprotection in gut microbiota-deleted mice. ImP, the downstream metabolite of <span style="font-variant: small-caps;">l</span>-Histidine, accumulated in peripheral blood and lung tissues following <span style="font-variant: small-caps;">l</span>-Histidine replenishment and protected against radiation-induced lung and heart toxicity. Orally gavaged ImP could not enter into the circulatory system in mice through an antibiotic cocktail treatment. Importantly, ImP inhibited pyroptosis to nudge lung cell proliferation after radiation challenge. Together, our findings pave a novel method of protection against cardiopulmonary complications intertwined with radiotherapy in pre-clinical settings and underpin the idea that gut microbiota-produced <span style="font-variant: small-caps;">l</span>-Histidine and ImP are promising radioprotective agents. |
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