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Meta-Analysis
. 2024 Jan-Dec;16(1):2350151.
doi: 10.1080/19490976.2024.2350151. Epub 2024 May 7.

Meta-analysis identifying gut microbial biomarkers of Qinghai-Tibet Plateau populations and the functionality of microbiota-derived butyrate in high-altitude adaptation

Hongwen Zhao  1 , Longjie Sun  1 , Jiali Liu  1 , Bin Shi  2 , Yaopeng Zhang  1 , Ci-Ren Qu-Zong  3   4 , Tsechoe Dorji  3 , Tieyu Wang  5 , Hongli Yuan  1 , Jinshui Yang  1
Affiliations
Meta-Analysis

Meta-analysis identifying gut microbial biomarkers of Qinghai-Tibet Plateau populations and the functionality of microbiota-derived butyrate in high-altitude adaptation

Hongwen Zhao et al. Gut Microbes. 2024 Jan-Dec.

Abstract

The extreme environmental conditions of a plateau seriously threaten human health. The relationship between gut microbiota and human health at high altitudes has been extensively investigated. However, no universal gut microbiota biomarkers have been identified in the plateau population, limiting research into gut microbiota and high-altitude adaptation. 668 16s rRNA samples were analyzed using meta-analysis to reduce batch effects and uncover microbiota biomarkers in the plateau population. Furthermore, the robustness of these biomarkers was validated. Mendelian randomization (MR) results indicated that Tibetan gut microbiota may mediate a reduced erythropoietic response. Functional analysis and qPCR revealed that butyrate may be a functional metabolite in high-altitude adaptation. A high-altitude rat model showed that butyrate reduced intestinal damage caused by high altitudes. According to cell experiments, butyrate may downregulate hypoxia-inducible factor-1α (HIF-1α) expression and blunt cellular responses to hypoxic stress. Our research found universally applicable biomarkers and investigated their potential roles in promoting human health at high altitudes.

Keywords: HIF-1α; Qinghai-Tibet plateau; butyrate; gut microbiota biomarker; high altitude adaptation.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Sample integration and analysis process.
Figure 2.
Figure 2.
Differences in gut microbiota between high- and low-altitude people.
Figure 3.
Figure 3.
Identification of gut microbiota biomarkers in plateau population.
Figure 4.
Figure 4.
Validation of predictive performance of gut microbiota biomarkers in plateau population.
Figure 5.
Figure 5.
The causal relationship between gut microbiome and altitude adaptation.
Figure 6.
Figure 6.
Changes in the abundance of gut microbiome SCFA-producing bacteria in high- and low-altitude population.
Figure 7.
Figure 7.
SCFA relieved intestinal damage caused by the plateau environment.
Figure 8.
Figure 8.
Butyrate alleviates intestinal damage caused by hypoxia by down-regulating HIF-1α in NCM460.
Figure 9.
Figure 9.
The potential mechanism of gut microbiota biomarkers to help maintain human health at the plateau.
See this image and copyright information in PMC

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References

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