# Metabolomic profiling and identification of potential biomarkers of highly pathogenic avian influenza (H5N1) in chicken

**Authors:** Althaf Mohammed Kadamthodi, Anuradha Panwar, Akhila Hosur Shrungeswara, Periyasamy Vijayakumar, Thottethodi Subrahmanya Keshava Prasad, Ashwin Ashok Raut, Anamika Mishra

PMC · DOI: 10.3389/fcimb.2025.1540290 · Frontiers in Cellular and Infection Microbiology · 2025-10-07

## TL;DR

This study identifies key metabolites in chickens infected with H5N1 avian influenza, offering insights into disease mechanisms and potential biomarkers.

## Contribution

First comprehensive metabolomic profiling of HPAI H5N1-infected chickens, identifying novel biomarkers and metabolic pathways.

## Key findings

- 31 and 13 altered metabolites identified in lung samples under positive and negative ionization modes.
- 22 and 15 altered metabolites found in serum samples under positive and negative ionization modes.
- Key metabolites like sphingosine and L-serine were significantly altered, impacting viral endocytosis and cell signaling.

## Abstract

Highly Pathogenic Avian Influenza (HPAI) H5N1 is a significant zoonotic pathogen with the potential to cause pandemics. Its high prevalence and mortality rates in poultry, along with a recent expansion in host range, underscore the urgent need to understand the molecular mechanisms underlying its pathogenesis and host-pathogen interactions. Metabolomics, the comprehensive study of small-molecule metabolites within biological systems, offers a promising approach to unravel these mechanisms and aid in the development of effective control strategies against HPAI H5N1.

To investigate the metabolomic alterations associated with HPAI H5N1 infection, serum and lung samples were collected from specific pathogen-free (SPF) chickens that were either infected with HPAI H5N1 or mock-infected as controls. Metabolomic profiling was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) under both positive and negative ionization modes. The resulting data were analyzed to identify metabolites that were significantly altered in response to infection.

The metabolomic analysis revealed substantial changes in both lung and serum samples following HPAI H5N1 infection. Specifically, 31 and 13 altered metabolites were identified in the lung, and 22 and 15 in the serum, under positive and negative ionization modes, respectively. Notably, key metabolites such as sphingosine, psychosine sulfate, and L-serine, which are known to influence viral endocytosis and cell signaling, were significantly altered in infected chickens.

The observed changes in sphingolipid and tryptophan metabolism provide insights into the mechanisms underlying lung and central nervous system (CNS) pathology associated with HPAI H5N1 infection. This study represents the first comprehensive metabolomic profiling of HPAI H5N1-infected chickens, offering valuable information for the development of novel therapeutics and control strategies. The identification of specific metabolite alterations may guide future research aimed at mitigating the impact of this highly pathogenic virus.

## Linked entities

- **Chemicals:** sphingosine (PubChem CID 5280335), psychosine sulfate (PubChem CID 5280538), L-serine (PubChem CID 5951)
- **Species:** Gallus gallus (taxon 9031)

## Full-text entities

- **Diseases:** HPAI H5N1 infection (MESH:D005585), infection (MESH:D007239)
- **Chemicals:** sphingosine (MESH:D013110), psychosine sulfate (-), tryptophan (MESH:D014364), L-serine (MESH:D012694), sphingolipid (MESH:D013107)
- **Species:** H5N1 subtype (serotype) [taxon 102793], Gallus gallus (bantam, species) [taxon 9031]

## Full text

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## Figures

12 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12537707/full.md

## References

44 references — full list in the complete paper: https://tomesphere.com/paper/PMC12537707/full.md

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Source: https://tomesphere.com/paper/PMC12537707