Abstract
Background
The contribution of gut microbiota to human high-altitude adaptation remains inadequately understood.
Methods
Here a comparative analysis of gut microbiota was conducted between healthy individuals living at sea level and high altitude using deep whole-metagenome shotgun sequencing, to investigate the adaptive mechanisms of gut microbiota in plateau inhabitants.
Results
The results showed the gut bacteriomes in high-altitude individuals exhibited greater within-sample diversity and significant alterations in both bacterial compositional and functional profiles when compared to those of sea-level individuals, indicating the potential selection of unique bacteria associated with high-altitude environments. The strain-level investigation revealed enrichment of Collinsella aerofaciens and Akkermansia muciniphila in high-altitude populations. The characteristics of gut virome and gut mycobiome were also investigated. Compared to sea-level subjects, high-altitude subjects exhibited a greater diversity in their gut virome, with an increased number of viral operational taxonomic units (vOTUs) and unique annotated genes. Finally, correlation analyses revealed 819 significant correlations between 42 bacterial species and 375 vOTUs, while no significant correlations were observed between bacteria and fungi or between fungi and viruses.
Conclusion
The findings have significantly contributed to an enhanced comprehension of the mechanisms underlying the high-altitude geographic adaptation of the human gut microbiota.
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Data availability
The raw metagenomic sequencing dataset for this study has been deposited in the European Nucleotide Archive (ENA) at EMBL-EBI under accession number PRJEB53209 (https://www.ebi.ac.uk/ena/browser/view/PRJEB53209). The authors declare that all other data supporting the findings of the study are available in the paper and supplementary materials, or from the corresponding author upon request.
Abbreviations
- BMI:
-
Body mass index;
- HA:
-
High-altitude;
- MAGs:
-
Metagenomic-assembled genomes;
- PCoA:
-
Principal coordinates analysis;
- SL:
-
Sea level;
- vOTUs:
-
Viral operational taxonomic units
References
Almeida A, Mitchell AL, Boland M, Forster SC, Gloor GB, Tarkowska A, Lawley TD, Finn RD (2019) A new genomic blueprint of the human gut microbiota. Nature 568(7753):499–504. https://doi.org/10.1038/s41586-019-0965-1
Almeida A, Nayfach S, Boland M, Strozzi F, Beracochea M, Shi ZJ, Pollard KS, Sakharova E, Parks DH, Hugenholtz P et al (2020) A unified catalog of 204,938 reference genomes from the human gut microbiome. Nat Biotechnol. https://doi.org/10.1038/s41587-020-0603-3
Asadi A, Shadab Mehr N, Mohamadi MH, Shokri F, Heidary M, Sadeghifard N, Khoshnood S (2022) Obesity and gut-microbiota-brain axis: A narrative review. J Clin Lab Anal 36(5):e24420. https://doi.org/10.1002/jcla.24420
Asnicar F, Thomas AM, Beghini F, Mengoni C, Manara S, Manghi P, Zhu Q, Bolzan M, Cumbo F, May U et al (2020) Precise phylogenetic analysis of microbial isolates and genomes from metagenomes using PhyloPhlAn 3.0. Nat Commun 11(1):2500. https://doi.org/10.1038/s41467-020-16366-7
Bae M, Cassilly CD, Liu X, Park SM, Tusi BK, Chen X, Kwon J, Filipcik P, Bolze AS, Liu Z et al (2022) Akkermansia muciniphila phospholipid induces homeostatic immune responses. Nature 608(7921):168–173. https://doi.org/10.1038/s41586-022-04985-7
Beghini F, McIver LJ, Blanco-Miguez A, Dubois L, Asnicar F, Maharjan S, Mailyan A, Manghi P, Scholz M, Thomas AM et al (2021) Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3. Elife 10:e65088. https://doi.org/10.7554/eLife.65088
Benler S, Yutin N, Antipov D, Rayko M, Shmakov S, Gussow AB, Pevzner P, Koonin EV (2021) Thousands of previously unknown phages discovered in whole-community human gut metagenomes. Microbiome 9(1):78. https://doi.org/10.1186/s40168-021-01017-w
Bin Jang H, Bolduc B, Zablocki O, Kuhn JH, Roux S, Adriaenssens EM, Brister JR, Kropinski AM, Krupovic M, Lavigne R et al (2019) Taxonomic assignment of uncultivated prokaryotic virus genomes is enabled by gene-sharing networks. Nat Biotechnol 37(6):632–639. https://doi.org/10.1038/s41587-019-0100-8
Camarillo-Guerrero LF, Almeida A, Rangel-Pineros G, Finn RD, Lawley TD (2021) Massive expansion of human gut bacteriophage diversity. Cell 184(4):1098-1109.e1099. https://doi.org/10.1016/j.cell.2021.01.029
Chaumeil PA, Mussig AJ, Hugenholtz P, Parks DH (2019) GTDB-Tk: a toolkit to classify genomes with the Genome Taxonomy Database. Bioinformatics. https://doi.org/10.1093/bioinformatics/btz848
Chen S, Zhou Y, Chen Y, Gu J (2018) fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 34(17):i884–i890. https://doi.org/10.1093/bioinformatics/bty560
Friedman J, Alm EJ (2012) Inferring correlation networks from genomic survey data. PLoS Comput Biol. 8(9):e1002687. https://doi.org/10.1371/journal.pcbi.1002687
Gomaa EZ (2020) Human gut microbiota/microbiome in health and diseases: a review. Antonie Van Leeuwenhoek 113(12):2019–2040. https://doi.org/10.1007/s10482-020-01474-7
Gregory AC, Zablocki O, Zayed AA, Howell A, Bolduc B, Sullivan MB (2020) The Gut Virome Database Reveals Age-Dependent Patterns of Virome Diversity in the Human Gut. Cell Host Microbe. 28(5):724-740 e728. https://doi.org/10.1016/j.chom.2020.08.003
Huo X, Li D, Wu F, Li S, Qiao Y, Wang C, Wang Y, Zhou C, Sun L, Luan Z et al (2022) Cultivated human intestinal fungus Candida metapsilosis M2006B attenuates colitis by secreting acyclic sesquiterpenoids as FXR agonists. Gut 71(11):2205–2217. https://doi.org/10.1136/gutjnl-2021-325413
Hyatt D, Chen GL, Locascio PF, Land ML, Larimer FW, Hauser LJ (2010) Prodigal: prokaryotic gene recognition and translation initiation site identification. BMC Bioinformatics 11:119. https://doi.org/10.1186/1471-2105-11-119
Jain C, Rodriguez RL, Phillippy AM, Konstantinidis KT, Aluru S (2018) High throughput ANI analysis of 90K prokaryotic genomes reveals clear species boundaries. Nat Commun 9(1):5114. https://doi.org/10.1038/s41467-018-07641-9
Jia Z, Zhao X, Liu X, Zhao L, Jia Q, Shi J, Xu X, Hao L, Xu Z, Zhong Q, et al (2020) Impacts of the plateau environment on the gut microbiota and blood clinical indexes in Han and Tibetan individuals. mSystems 5(1):e00660–19. https://doi.org/10.1128/mSystems.00660-19
Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K (2017) KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res 45(D1):D353–D361. https://doi.org/10.1093/nar/gkw1092
Kang DD, Li F, Kirton E, Thomas A, Egan R, An H, Wang Z (2019) MetaBAT 2: an adaptive binning algorithm for robust and efficient genome reconstruction from metagenome assemblies. PeerJ 7:e7359. https://doi.org/10.7717/peerj.7359
Kieft K, Zhou Z, Anantharaman K (2020) VIBRANT: automated recovery, annotation and curation of microbial viruses, and evaluation of viral community function from genomic sequences. Microbiome 8(1):90. https://doi.org/10.1186/s40168-020-00867-0
Lan D, Ji W, Lin B, Chen Y, Huang C, Xiong X, Fu M, Mipam TD, Ai Y, Zeng B et al (2017) Correlations between gut microbiota community structures of Tibetans and geography. Sci Rep 7(1):16982. https://doi.org/10.1038/s41598-017-17194-4
Langmead B, Salzberg SL (2012) Fast gapped-read alignment with Bowtie 2. Nat Methods 9(4):357–359. https://doi.org/10.1038/nmeth.1923
Lee JY, Tsolis RM, Baumler AJ (2022) The microbiome and gut homeostasis. Science. 377(6601):abp9960. https://doi.org/10.1126/science.abp9960
Li D, Liu CM, Luo R, Sadakane K, Lam TW (2015) MEGAHIT: an ultra-fast single-node solution for large and complex metagenomics assembly via succinct de Bruijn graph. Bioinformatics 31(10):1674–1676. https://doi.org/10.1093/bioinformatics/btv033
Li K, Dan Z, Gesang L, Wang H, Zhou Y, Du Y, Ren Y, Shi Y, Nie Y (2016) Comparative Analysis of Gut Microbiota of Native Tibetan and Han Populations Living at Different Altitudes. PLoS One. 11(5):e0155863. https://doi.org/10.1371/journal.pone.0155863
Liu Z, Li J, Liu H, Tang Y, Zhan Q, Lai W, Ao L, Meng X, Ren H, Xu D et al (2019) The intestinal microbiota associated with cardiac valve calcification differs from that of coronary artery disease. Atherosclerosis 284:121–128. https://doi.org/10.1016/j.atherosclerosis.2018.11.038
Michels N, Zouiouich S, Vanderbauwhede B, Vanacker J, Indave Ruiz BI, Huybrechts I (2022) Human microbiome and metabolic health: An overview of systematic reviews. Obes Rev 23(4):e13409. https://doi.org/10.1111/obr.13409
Nayfach S, Shi ZJ, Seshadri R, Pollard KS, Kyrpides NC (2019) New insights from uncultivated genomes of the global human gut microbiome. Nature 568(7753):505–510. https://doi.org/10.1038/s41586-019-1058-x
Nayfach S, Camargo AP, Schulz F, Eloe-Fadrosh E, Roux S, Kyrpides NC (2020) CheckV assesses the quality and completeness of metagenome-assembled viral genomes. Nat Biotechnol. https://doi.org/10.1038/s41587-020-00774-7
Nayfach S, Paez-Espino D, Call L, Low SJ, Sberro H, Ivanova NN, Proal AD, Fischbach MA, Bhatt AS, Hugenholtz P et al (2021) Metagenomic compendium of 189,680 DNA viruses from the human gut microbiome. Nat Microbiol. 6(7):960–970. https://doi.org/10.1038/s41564-021-00928-6
Nousias O, Montesanto F (2021) Metagenomic profiling of host-associated bacteria from 8 datasets of the red alga Porphyra purpurea with MetaPhlAn3. Mar Genomics 59:100866. https://doi.org/10.1016/j.margen.2021.100866
Parks DH, Imelfort M, Skennerton CT, Hugenholtz P, Tyson GW (2015) CheckM: assessing the quality of microbial genomes recovered from isolates, single cells, and metagenomes. Genome Res 25(7):1043–1055. https://doi.org/10.1101/gr.186072.114
Pasolli E, Asnicar F, Manara S, Zolfo M, Karcher N, Armanini F, Beghini F, Manghi P, Tett A, Ghensi P et al (2019) Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and Lifestyle. Cell. 176(3):649-662 e620. https://doi.org/10.1016/j.cell.2019.01.001
Poole AC, Goodrich JK, Youngblut ND, Luque GG, Ruaud A, Sutter JL, Waters JL, Shi Q, El-Hadidi M, Johnson LM et al (2019) Human Salivary Amylase Gene Copy Number Impacts Oral and Gut Microbiomes. Cell Host Microbe. 25(4):553-564 e557. https://doi.org/10.1016/j.chom.2019.03.001
Ren J, Ahlgren NA, Lu YY, Fuhrman JA, Sun F (2017) VirFinder: a novel k-mer based tool for identifying viral sequences from assembled metagenomic data. Microbiome 5(1):69. https://doi.org/10.1186/s40168-017-0283-5
Siranosian BA, Tamburini FB, Sherlock G, Bhatt AS (2020) Acquisition, transmission and strain diversity of human gut-colonizing crAss-like phages. Nat Commun 11(1):280. https://doi.org/10.1038/s41467-019-14103-3
Su G, Morris JH, Demchak B, Bader GD (2014) Biological network exploration with Cytoscape 3. Curr Protoc Bioinformatics 47:8.13.1–8.13.24. https://doi.org/10.1002/0471250953.bi0813s47
Sun Y, Zuo T, Cheung CP, Gu W, Wan Y, Zhang F, Chen N, Zhan H, Yeoh YK, Niu J et al (2021) Population-Level Configurations of Gut Mycobiome Across 6 Ethnicities in Urban and Rural China. Gastroenterology 160(1):272-286 e211. https://doi.org/10.1053/j.gastro.2020.09.014
Szilagyi A (2015) Adaptation to Lactose in Lactase Non Persistent People: Effects on Intolerance and the Relationship between Dairy Food Consumption and Evalution of Diseases. Nutrients 7(8):6751–6779. https://doi.org/10.3390/nu7085309
Yan Q, Wang Y, Chen X, Jin H, Wang G, Guan K, Zhang Y, Zhang P, Ayaz T, Liang Y et al (2021) Characterization of the gut DNA and RNA Viromes in a Cohort of Chinese Residents and Visiting Pakistanis. Virus Evol. 7(1):veab022. https://doi.org/10.1093/ve/veab022
Zuo T, Sun Y, Wan Y, Yeoh YK, Zhang F, Cheung CP, Chen N, Luo J, Wang W, Sung JJY et al (2020) Human-Gut-DNA Virome Variations across Geography, Ethnicity, and Urbanization. Cell Host Microbe. 28(5):741-751 e744. https://doi.org/10.1016/j.chom.2020.08.005
Funding
This work was supported by Characteristic Technology of Polysaccharides Research Programme of Naqu, Tibet [grant number QYXTZX-NQ2022-03] and the National Natural Science Foundation of China [grant number 82370563, 31700697].
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Zhen Xiao: Methodology, Formal analysis, Visualization, Investigation, Writing-original draft. Yue Zhang: Methodology, Formal analysis, Visualization, Investigation, Data curation. Wei Zhang: Visualization, Investigation. Aiqin Zhang: Visualization, Investigation. Guangyang Wang: Visualization, Investigation. Changming Chen: Visualization, Investigation. Hayan Ullah: Visualization, Investigation. Taj Ayaz: Visualization, Investigation. Shenghui Li: Methodology, Data curation. Duoji Zhaxi: Visualization, Investigation. Jian Kang: Conceptualization, Methodology, Validation, Supervision, Writing-review & editing Funding acquisition. Qiulong Yan: Conceptualization, Methodology, Validation, Supervision, Writing-original draft, Funding acquisition. Xiaoguang Xu: Conceptualization, Methodology, Validation, Supervision, Funding acquisition, resources.
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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of People’s Hospital of Naqu (Tibet) and the First Affiliated Hospital of Dalian Medical University (Liaoning).
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Xiao, Z., Zhang, Y., Zhang, W. et al. Characterizations of gut bacteriome, mycobiome, and virome of healthy individuals living in sea-level and high-altitude areas. Int Microbiol (2024). https://doi.org/10.1007/s10123-024-00531-9
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DOI: https://doi.org/10.1007/s10123-024-00531-9