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Metagenomic sequencing reveals altered gut microbiota of sojourners at high altitude: a longitudinal study

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Abstract

Human microbial alterations are associated with environmental stress, nutrition, genetic, and triggering de-novo variations. Nevertheless, the human gut microbiome at extreme altitude (> 5800 m) remains unexplored. We aimed to demonstrate the microbial predominance in individuals with the same ethnicity and dietary pattern at extreme altitude with unique challenges like cold, hypoxia, radiation, etc. Different analysis pipelines were used for fecal whole genome sequencing at 210 m, 3500 m, 4420 m and 5805 m, and 16S rRNA V3-V4 regions amplification sequencing of 19 individuals belonging to the same ethnicity and dietary pattern for the presence of taxonomy and functional potential and confirming the prediction up to the strain level within the same cohort. Principal component analysis revealed distinct microbiome changes at different altitudes, with varied and higher Bacteroides and Prevotella ratio. There was a predominance of genus Prevotella at altitudes 4420 m and 5805 m than at 210 m and 3500 m. The appearance of species Prevotella copri strain 61,740 increased significantly at extreme altitude, whereas co-occurrence of other bacterial strains had a different pattern than Prevotella. The extensive strain-level analysis indicated alteration in the metabolic pathways. This study under the stressful and hypoxic environment of extreme altitudes, associated microbial variation with altered metabolic pathways, reveals the influence of extreme environment on human gut microbiota with the predominance of Prevotella.

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Sequencing data reported in this paper is available at NCBI under the project no. PRJNA492714.

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Acknowledgements

Authors thank DRDO for funding. Also, NXGenBio is greatly acknowledged for data assembly and analysis. All the sojourns are accredited for participating in the study.

Funding

This work is supported by Defence Research and Development Organization.

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Authors and Affiliations

  1. Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research Development Organization (DRDO), Lucknow Road, Timarpur, Delhi, 110054, India

    Brij Bhushan, M. R. Eslavath, A. P. Yadav, A. K. Srivastava, M. P. K. Reddy, B. Kumar & L. Ganju

  2. Ladakh Institute for Prevention (LIP), Dambuchan, Leh-Ladakh, Jammu and Kashmir, 194101, India

    T. Norboo

  3. National Institute of Pharmaceuticals Education and Research (NIPER), Balanagar, Hyderabad, Telangana, 500037, India

    S. B. Singh

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  1. Brij Bhushan
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  2. M. R. Eslavath
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  3. A. P. Yadav
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  4. A. K. Srivastava
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  5. M. P. K. Reddy
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  9. L. Ganju
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Contributions

LG, SBS and BK devised the project, designed the study protocol and supervised all phases of the project. BB, APY and MRE performed sample collection and DNA extraction. LG and BB carried out subjects phenoty**, data interpretation and analyses, and wrote the manuscript. MPKR and TN arranged for subjects availability and provided logistics support at high latitude. AKS participated in sample collection at baseline, DNA extraction and library preparations. All authors contributed to data interpretation, discussions and editing of the paper.

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Correspondence to L. Ganju.

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All expedition participants understood the nature of the study and gave the written consent. The ethics committee of Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Delhi, India approved all the relevant parameters of the study. The study protocols were in accordance with the Helsinki’s approved guidelines.

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Bhushan, B., Eslavath, M.R., Yadav, A.P. et al. Metagenomic sequencing reveals altered gut microbiota of sojourners at high altitude: a longitudinal study. J Proteins Proteom 12, 271–288 (2021). https://doi.org/10.1007/s42485-021-00077-8

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