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

  • NPJ Biofilms Microbiomes. 2025 Jul 1;11(1):116. doi: 10.1038/s41522-025-00753-3.
JunHong Xing  #  1 ,  TianMing Niu  #  1 ,  Tong Yu  #  1 ,  BoShi Zou  1 ,  ShuHui Fan  1 ,  ChunFeng Wang  1 ,  ChunWei Shi  1 ,  DongXing Zhang  1 ,  Nan Wang  1 ,  YanLong Jiang  1 ,  HaiBin Huang  1 ,  Xin Cao  1 ,  Yan Zeng  1 ,  JianZhong Wang  1 ,  Di Zhang  2 ,  GuiLian Yang  3 ,  WenTao Yang  4
Affiliations
  • 1. 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. 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. [email protected].
  • 3. 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. [email protected].
  • 4. 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. [email protected].
  • # Contributed equally.
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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