Altitude‐dependent metabolite biomarkers reveal the mechanism of plateau pika adaptation to high altitudes

Abstract

The harsh environment in the Tibetan plateau, the highest place in the world, poses thermoregulatory challenges and hypoxic stress to animals. The impacts of plateau environment on animal physiology and reproduction include external factors such as strong ultraviolet radiation and low temperature, and internal factors such as animal metabolites and gut microbiota. However, it remains unclear how plateau pika adapt to high altitudes through the combination of serum metabolites and gut microbiota. To this end, we captured 24 wild plateau pikas at the altitudes of 3400, 3600, or 3800 m a.s.l. in a Tibetan alpine grassland. Using the machine learning algorithms (random forest), we identified five biomarkers of serum metabolites indicative of the altitudes, that is, dihydrotestosterone, homo‐l‐arginine, alpha‐ketoglutaric‐acid, serotonin, and threonine, which were related to body weight, reproduction, and energy metabolism of pika. Those metabolic biomarkers were positively correlated with Lachnospiraceae_ Agathobacter, Ruminococcaceae, or Prevotellaceae_Prevotella, suggesting the close relationship between metabolites and gut microbiota. By identifying the metabolic biomarkers and gut microbiota analysis, we reveal the mechanisms of adaptation to high altitudes in plateau pika.

Impaired Indole Acetic Acid and Reduced Indole-Producing Bacteria Contribute to Swainsonine-Induced Liver Inflammation

“…In OPLS-DA model, R 2 X represented the cumulative explanatory rate of the model in the X -axis direction, and Q 2 represented the cumulative prediction rate of the model when modeling the multivariate statistical analysis. In theory, when the values of R 2 X and Q 2 were closer to 1, indicating a better model, and it was acceptable when R 2 X and Q 2 were higher than 0.4 . In Figure , the control group and the swainsonine-treated groups were distributed on both sides of the y -axis, and the R 2 X values and Q 2 values were greater than 0.4, indicating that their metabolites in the serum and liver were significantly different after swainsonine treatment compared to the control.…”

“…In theory, when the values of R 2 X and Q 2 were closer to 1, indicating a better model, and it was acceptable when R 2 X and Q 2 were higher than 0.4. 24 In Figure 1, the control group and the swainsonine-treated groups were distributed on both sides of the y-axis, and the R 2 X values and Q 2 values were greater than 0.4, indicating that their metabolites in the serum and liver were significantly different after swainsonine treatment compared to the control. The permutation tests further verified the validity of the models (Figure S3A−F).…”

Male infertility risk and gut microbiota: a Mendelian randomization study

“…Mice with metabolic syndrome (Mets) have abnormal testicular spermatogenesis due to impaired vitamin A absorption in the intestine, which may be associated with the significantly reduced abundance of Ruminococcaceae (NK4A214group) (Zhang et al, 2022 ). As an androgen found in epididymal cells, dihydrotestosterone (DHT) regulates sperm maturation (Robaire and Henderson, 2006 ), and a large-scale animal study suggested that an abundance of Ruminococcaceae was positively correlated with DHT (Chen et al, 2023 ). Regulation of the gut microbiota to improve the symptoms of drug-induced male infertility was demonstrated by several studies (Zhao et al, 2020b ; Sun et al, 2022 ).…”

Temporal and geographic distribution of gut microbial enterotypes associated with host thermogenesis characteristics in plateau pikas

“…The samples collected in August and January represent warm and cold seasons, respectively. According to the physiological and reproductive characteristic of plateau pikas ( 73 – 76 ), we defined the samples collected over altitude 3,900 m as high altitudinal samples, while the samples collected below 3,900 m were defined as low altitudinal samples. On average, 10 individuals were randomly captured at each sampling site.…”