A Systematic Comparison of Differential Metabolites and Functional Pathways in the Gut Contents of Yaks and Plateau Yellow Cattle Across Altitudinal Gradients.
- 1State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, College of Veterinary Medicine, Lanzhou University, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.
- 2Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou 730046, China.
- 3Institute of Livestock, Grass, and Green Agriculture, Gansu Academy of Agricultural Sciences, Lanzhou 730070, China.
Abstract
The yak (Bos grunniens) is a crucial species adapted to the extreme high-altitude environment of the Tibetan Plateau. However, a systematic understanding of how gut metabolic homeostasis contributes to this adaptation, particularly across altitudinal gradients and in comparison with sympatric species, remains limited. This study employed untargeted metabolomics to profile the intestinal contents of high-altitude yaks (HYs, 3800 m), low-altitude yaks (LYs, 2500 m), and plateau yellow cattle (PC, 3500 m) from the Gannan region. Multivariate analysis revealed distinct clustering of the three groups, with PLS-DA model validation parameters (R₂Y(cum) > 0.997, Q₂(cum) > 0.990), confirming significant species-specific and altitude-adaptive differentiation in the gut metabolome. A suite of differentially abundant metabolites (DAMs) was identified: HYs were enriched with stress- and inflammation-related molecules (e.g., prostaglandin E2, uric acid-indicative of oxidative stress and inflammatory responses) and steroid metabolites; LYs showed a profile oriented towards basic anabolism and antioxidant defense (e.g., L-galactono-1,4-lactone, allantoin); PC were characterized by unique lipid derivatives (e.g., 5-hexyl-2-furanhexanoic acid) and fungal-origin metabolites. Pathway enrichment analysis pinpointed Linoleic acid metabolism as one of the most significantly enriched pathways, with key hydroxyoctadecadienoic acids (HODEs) and related oxylipins significantly upregulated in HYs. Other significantly enriched pathways included Tryptophan metabolism, ABC transporters, and Protein digestion and absorption. Our findings suggest that high-altitude adaptation in yaks is associated with remodeling of the intestinal metabolic network. The identified signature metabolites and consistently enriched candidate pathways provide novel insights into potential host-microbiome-associated mechanisms and establish a metabolic foundation for the conservation of plateau livestock genetic resources and the development of precision husbandry strategies. However, these findings should be interpreted as hypothesis-generating because altitude, species, diet, and environment were not fully decoupled.
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BibTeX
@article{li2026systematic,
title = {{A Systematic Comparison of Differential Metabolites and Functional Pathways in the Gut Contents of Yaks and Plateau Yellow Cattle Across Altitudinal Gradients.}},
author = {Dan Li and Jian Zhang and Liping Zhang and Xinsheng Liu and Ping Chen},
journal = {Veterinary sciences},
year = {2026},
month = oct,
doi = {10.3390/vetsci13101063},
url = {https://europepmc.org/article/MED/42944158},
note = {CC BY},
}
RIS
TY - JOUR
TI - A Systematic Comparison of Differential Metabolites and Functional Pathways in the Gut Contents of Yaks and Plateau Yellow Cattle Across Altitudinal Gradients.
AU - Dan Li
AU - Jian Zhang
AU - Liping Zhang
AU - Xinsheng Liu
AU - Ping Chen
PY - 2026
DA - 2026/10/09
JO - Veterinary sciences
DO - 10.3390/vetsci13101063
UR - https://europepmc.org/article/MED/42944158
AB - The yak (Bos grunniens) is a crucial species adapted to the extreme high-altitude environment of the Tibetan Plateau. However, a systematic understanding of how gut metabolic homeostasis contributes to this adaptation, particularly across altitudinal gradients and in comparison with sympatric species, remains limited. This study employed untargeted metabolomics to profile the intestinal contents of high-altitude yaks (HYs, 3800 m), low-altitude yaks (LYs, 2500 m), and plateau yellow cattle (PC, 3500 m) from the Gannan region. Multivariate analysis revealed distinct clustering of the three groups, with PLS-DA model validation parameters (R₂Y(cum) > 0.997, Q₂(cum) > 0.990), confirming significant species-specific and altitude-adaptive differentiation in the gut metabolome. A suite of differentially abundant metabolites (DAMs) was identified: HYs were enriched with stress- and inflammation-related molecules (e.g., prostaglandin E2, uric acid-indicative of oxidative stress and inflammatory responses) and steroid metabolites; LYs showed a profile oriented towards basic anabolism and antioxidant defense (e.g., L-galactono-1,4-lactone, allantoin); PC were characterized by unique lipid derivatives (e.g., 5-hexyl-2-furanhexanoic acid) and fungal-origin metabolites. Pathway enrichment analysis pinpointed Linoleic acid metabolism as one of the most significantly enriched pathways, with key hydroxyoctadecadienoic acids (HODEs) and related oxylipins significantly upregulated in HYs. Other significantly enriched pathways included Tryptophan metabolism, ABC transporters, and Protein digestion and absorption. Our findings suggest that high-altitude adaptation in yaks is associated with remodeling of the intestinal metabolic network. The identified signature metabolites and consistently enriched candidate pathways provide novel insights into potential host-microbiome-associated mechanisms and establish a metabolic foundation for the conservation of plateau livestock genetic resources and the development of precision husbandry strategies. However, these findings should be interpreted as hypothesis-generating because altitude, species, diet, and environment were not fully decoupled.
SN - 2306-7381
ER -