Reconstruction of ancient microbial genomes from the human gut

Marsha C. Wibowo, Zhen Yang, Maxime Borry, Alexander Hübner, Kun D. Huang, Braden T. Tierney, Samuel Zimmerman, Francisco Barajas-Olmos, Cecilia Contreras-Cubas, Humberto García-Ortiz, Angélica Martínez-Hernández, Jacob M. Luber, Philipp Kirstahler, Tre Blohm, Francis E. Smiley, Richard Arnold, Sonia A. Ballal, Sünje Johanna Pamp, Julia Russ, Frank MaixnerOmar Rota-Stabelli, Nicola Segata, Karl Reinhard, Lorena Orozco, Christina Warinner, Meradeth Snow, Steven LeBlanc, Aleksandar D. Kostic

Research output: Contribution to journalArticlepeer-review

166 Scopus citations

Abstract

Loss of gut microbial diversity1–6 in industrial populations is associated with chronic diseases7, underscoring the importance of studying our ancestral gut microbiome. However, relatively little is known about the composition of pre-industrial gut microbiomes. Here we performed a large-scale de novo assembly of microbial genomes from palaeofaeces. From eight authenticated human palaeofaeces samples (1,000–2,000 years old) with well-preserved DNA from southwestern USA and Mexico, we reconstructed 498 medium- and high-quality microbial genomes. Among the 181 genomes with the strongest evidence of being ancient and of human gut origin, 39% represent previously undescribed species-level genome bins. Tip dating suggests an approximate diversification timeline for the key human symbiont Methanobrevibacter smithii. In comparison to 789 present-day human gut microbiome samples from eight countries, the palaeofaeces samples are more similar to non-industrialized than industrialized human gut microbiomes. Functional profiling of the palaeofaeces samples reveals a markedly lower abundance of antibiotic-resistance and mucin-degrading genes, as well as enrichment of mobile genetic elements relative to industrial gut microbiomes. This study facilitates the discovery and characterization of previously undescribed gut microorganisms from ancient microbiomes and the investigation of the evolutionary history of the human gut microbiota through genome reconstruction from palaeofaeces.

Original languageEnglish
Pages (from-to)234-239
Number of pages6
JournalNature
Volume594
Issue number7862
DOIs
StatePublished - Jun 10 2021

Funding

Paleofeces were collected from Boomerang Shelter, Arid West Cave, and La Cueva de los Muertos Chiquitos (Zape). Boomerang shelter lies in southeastern Utah and was excavated under Utah Antiquities Section, permit number U-01-NO. For the Arid West Cave site, a series of dry rock shelters were excavated, most likely from the Rasmussen Ranch Cave site in east central Utah, between the years 1920-1931 under an antiquities permit as discussed in previous publications (Morss et al., 1931; Morss et al., 1931; Spangler et al., 2018). For Zape, the cave was excavated in April 1957 and July 1960 by Richard Brooks, assisted by Sheilagh Brooks and Teodoro Corral. The work was supported by a grant from the Associates in Tropical Biogeography of the University of California. Permission to excavate was granted by the Mexican government through the Secre-taria de Educacion Publica. Ignacio Bernal and his colleagues in the Instituto Nacional de Antropologia e Historia assisted. Acknowledgements We acknowledge and appreciate those individuals whose genetics and microorganisms were analysed for this research, as well as present-day individuals with associated genetic or cultural heritage. We thank members of the A.D.K. laboratory, especially T. A. Chavkin and M. Tran for discussion and reading of the manuscript, and L.-D. Pham for assistance with construction of sequencing libraries; J. A. Fellows Yates and A. B. Rohrlach for discussion, advice on metagenomic analysis and reading of the manuscript; Y.-H. Tseng for guidance and members of the Y.-H. Tseng laboratory for discussions; M. L. Taylor and R. J. Wheeler from the Robert S. Peabody Institute of Archaeology for their roles in initiating and assisting with consultation with Native American communities. Parasite-related sequence analysis was performed using the DeiC National Life Science Supercomputer at the Technical University of Denmark. This research was supported by the American Diabetes Association (ADA) Pathway to Stop Diabetes Initiator Award 1-17-INI-13 (A.D.K.), a Smith Family Foundation Award for Excellence in Biomedical Research (A.D.K.), the American Heart Association (AHA) Predoctoral Fellowship 19PRE34430165 (M.C.W.), a European Research Council grant ERC-STG Project MetaPG (N.S.), Werner Siemens Stiftung (M.B. and C.W.) and by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy EXC 2051, Project-ID 390713860 (A.H. and C.W.). Support was also provided by NIH grant no. P30DK036836-30 (principal investigator, G. L. King).

FundersFunder number
American Diabetes Association1-17-INI-13
P30DK036836
American Heart Association19PRE34430165
California State University Stanislaus
390713860, EXC 2051

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