Faecalibacterium prausnitzii in the gut protects against acute lung injury in influenza through butyrate educated reparative CD4⁺T cells.
12 affiliations
- 1Department of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- 2Zhejiang Key Laboratory of Clinical In Vitro Diagnostic Techniques, Hangzhou, China.
- 3Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China.
- 4Department of Clinical Laboratory, School of Medicine, Affiliated Hangzhou First People's Hospital, Westlake University, Hangzhou, Zhejiang, China.
- 5State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
- 6Department of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. [email protected].
- 7Zhejiang Key Laboratory of Clinical In Vitro Diagnostic Techniques, Hangzhou, China. [email protected].
- 8Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China. [email protected].
- 9Department of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. [email protected].
- 10Zhejiang Key Laboratory of Clinical In Vitro Diagnostic Techniques, Hangzhou, China. [email protected].
- 11Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China. [email protected].
- 12State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China. [email protected].
Abstract
Background
Uncontrolled pneumonia induced by influenza virus infection results in severe lung pathology. Timely and proper tissue self-repair is critical to improve survival. This study aimed to identify probiotic strains that confer protection against acute lung injury induced by influenza virus infection and to elucidate the underlying molecular mechanisms.Results
Significant structural alterations in the gut microbiota were observed in influenza patients, characterized by a marked depletion in Faecalibacterium prausnitzii, whose abundance was negatively correlated with disease severity. In a murine model of influenza infection, oral administration of Faecalibacterium prausnitzii and its culture supernatant markedly alleviated lung injury. Targeted metabolomic analysis identified butyrate as the principal metabolite produced by Faecalibacterium prausnitzii that mediates lung tissue protection. Single-cell RNA sequencing further revealed that butyrate promotes the differentiation of pulmonary CD4⁺T cells into a reparative phenotype with enhanced interleukin-22 (IL-22) production. Mechanistically, butyrate facilitates IL-22 secretion through monounsaturated fatty acid biosynthesis via a histone-acetylation-dependent NR4A1-SCD1 axis. Accumulated monounsaturated fatty acids further enhance mitochondrial activities, which are essential for robust IL-22 production. Utilizing an IL-22 knockout mouse model, we confirmed the indispensable protective role of IL-22 in this gut-lung axis during influenza infection.Conclusion
Our findings demonstrate that butyrate, derived from intestinal commensal Faecalibacterium prausnitzii, plays a crucial role in maintaining pulmonary tissue homeostasis during influenza infection by modulating intrinsic lipid metabolism in CD4⁺T cells. This study underscores the promising translational potential of Faecalibacterium prausnitzii supplementation as an innovative therapeutic strategy for severe influenza-associated lung injury. Video Abstract.
Related
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BibTeX
@article{mao2026faecalibacterium,
title = {{Faecalibacterium prausnitzii in the gut protects against acute lung injury in influenza through butyrate educated reparative CD4⁺T cells.}},
author = {Zheying Mao and Liqian Wang and Chenyue Zhuo and Mingzhu Huang and Jili Ni and Chang Liu and Weizhen Chen and Jiaqi Bao and Bin Lou and Haiying Yu and Shufa Zheng and Yu Chen},
journal = {Microbiome},
year = {2026},
month = jul,
doi = {10.1186/s40168-026-02486-7},
url = {https://europepmc.org/article/MED/42934798},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Faecalibacterium prausnitzii in the gut protects against acute lung injury in influenza through butyrate educated reparative CD4⁺T cells.
AU - Zheying Mao
AU - Liqian Wang
AU - Chenyue Zhuo
AU - Mingzhu Huang
AU - Jili Ni
AU - Chang Liu
AU - Weizhen Chen
AU - Jiaqi Bao
AU - Bin Lou
AU - Haiying Yu
AU - Shufa Zheng
AU - Yu Chen
PY - 2026
DA - 2026/07/30
JO - Microbiome
DO - 10.1186/s40168-026-02486-7
UR - https://europepmc.org/article/MED/42934798
AB - Background Uncontrolled pneumonia induced by influenza virus infection results in severe lung pathology. Timely and proper tissue self-repair is critical to improve survival. This study aimed to identify probiotic strains that confer protection against acute lung injury induced by influenza virus infection and to elucidate the underlying molecular mechanisms.Results Significant structural alterations in the gut microbiota were observed in influenza patients, characterized by a marked depletion in Faecalibacterium prausnitzii, whose abundance was negatively correlated with disease severity. In a murine model of influenza infection, oral administration of Faecalibacterium prausnitzii and its culture supernatant markedly alleviated lung injury. Targeted metabolomic analysis identified butyrate as the principal metabolite produced by Faecalibacterium prausnitzii that mediates lung tissue protection. Single-cell RNA sequencing further revealed that butyrate promotes the differentiation of pulmonary CD4⁺T cells into a reparative phenotype with enhanced interleukin-22 (IL-22) production. Mechanistically, butyrate facilitates IL-22 secretion through monounsaturated fatty acid biosynthesis via a histone-acetylation-dependent NR4A1-SCD1 axis. Accumulated monounsaturated fatty acids further enhance mitochondrial activities, which are essential for robust IL-22 production. Utilizing an IL-22 knockout mouse model, we confirmed the indispensable protective role of IL-22 in this gut-lung axis during influenza infection.Conclusion Our findings demonstrate that butyrate, derived from intestinal commensal Faecalibacterium prausnitzii, plays a crucial role in maintaining pulmonary tissue homeostasis during influenza infection by modulating intrinsic lipid metabolism in CD4⁺T cells. This study underscores the promising translational potential of Faecalibacterium prausnitzii supplementation as an innovative therapeutic strategy for severe influenza-associated lung injury. Video Abstract.
SN - 2049-2618
ER -