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NPJ biofilms and microbiomes
Jul 01, 2025;11 (1): 116.

Gut microbiota-derived isovaleric acid ameliorates influenza virus infection via gut-lung axis.

JunHong Xing, TianMing Niu, Tong Yu, BoShi Zou, ShuHui Fan, ChunFeng Wang, ChunWei Shi, DongXing Zhang, Nan Wang, YanLong Jiang, HaiBin Huang, Xin Cao, Yan Zeng, JianZhong Wang, Di Zhang, GuiLian Yang, WenTao Yang
Author Information
  1. JunHong Xing: College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China.
  2. TianMing Niu: College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China.
  3. Tong Yu: College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China.
  4. BoShi Zou: College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China.
  5. ShuHui Fan: College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China.
  6. ChunFeng Wang: College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China.
  7. ChunWei Shi: College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China.
  8. DongXing Zhang: College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China.
  9. Nan Wang: College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China.
  10. YanLong Jiang: College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China.
  11. HaiBin Huang: College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China.
  12. Xin Cao: College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China.
  13. Yan Zeng: College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China.
  14. JianZhong Wang: College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China.
  15. Di Zhang: College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China. zhangdi@jlau.edu.cn.
  16. GuiLian Yang: College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China. yangguilian@jlau.edu.cn.
  17. WenTao Yang: College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China. yangwentao@jlau.edu.cn.
PMID: 40593739 DOI: 10.1038/s41522-025-00753-3

Abstract

H9N2 influenza virus infections represent a significant respiratory health concern, yet the functional role of gut microbiota during infection progression remains poorly understood. Here, we show that H9N2 infection causes dose-dependent alterations in gut microbial communities in a mammalian infection model, particularly the depletion of Prevotella species. Prophylactic administration of Prevotella copri improved survival and clinical outcomes in infected mice by restructuring the gut microbiome, promoting beneficial bacteria, and suppressing pathogens. Metabolomic profiling revealed increased isovaleric acid levels in the intestine and serum. Isovaleric acid pretreatment reduced pulmonary inflammation, alleviated tissue damage, and preserved epithelial integrity. Isovaleric acid pretreatment alleviates lung inflammation, reduces tissue damage, and maintains epithelial integrity. Additionally, isovaleric acid mitigates infection caused by the H1N1 influenza virus. These findings highlight the immunomodulatory role of gut commensals and their metabolites in antiviral defense, offering a new approach to influenza virus treatment.

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Grants

  1. U21A20261/National Natural Science Foundation of China

MeSH Term

Animals
Gastrointestinal Microbiome
Orthomyxoviridae Infections
Mice
Influenza A Virus, H1N1 Subtype
Lung
Influenza A Virus, H9N2 Subtype
Disease Models, Animal
Prevotella
Pentanoic Acids
Hemiterpenes

Chemicals

isovaleric acid
Pentanoic Acids
Hemiterpenes
Journal Article

Word Cloud

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