Research

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LMAMR Projects

MICROBIAL ECOL

Evolution and Ecology of the Human Gut Microbiome

The human body contains approximately 100 trillion cells, of which more than 90 percent are microbial. These underexplored and mostly nameless microorganisms, collectively known as the human microbiome, weigh about as much as the human brain and harbor an immense diversity of genes that far exceed the functional capacity of our own genome, playing critical roles in digestion, vitamin production, drug metabolism, and immunity. It is becoming increasingly clear that no study of human health or evolution is complete without consideration of our microbial self. And yet, while we have made great strides in revealing the diversity, variation, and evolution of the human genome, we know surprisingly little about the origins and diversity of the microbial portion of ourselves.

Until very recently, nearly all studies of human evolution focused on the ten percent of our cells and 0.7 percent of our genes that we conventionally call human. How has the other 90 percent of our cells and 99.3 percent of our hologenome evolved through time? Moreover, with few exceptions, even studies of the human microbiome have focused almost exclusively on Western industrialized societies, presenting a severe sampling bias that favors affluent metropolitan groups, potentially fostering downstream health disparities for under-represented peoples.

Focusing on fecal samples from diverse living populations and well-preserved archaeological sites, this study seeks to address fundamental questions about the evolution and ecology of the human gut microbiome, including: How did the primate gut evolve and adapt to climate and habitat changes? Were certain microbes passed down, mother to child, forming a unique aspect of heritability? What role did microbes and their diverse genetic functions play as hominins expanded into new continents and as humans transitioned from low-density bands of hunter-gatherers to dense urban-dwelling populations reliant on industrial agriculture and globalized supply chains? How do gut microbiomes vary today among living populations, and what consequences do these differences have on health and disease?

Publications resulting thus far from this project include:

Sankaranarayanan KOzga ATWarinner CTito RYObregon-Tito AJXu J, Gaffney PM, Jervis L, Cox D, Stephens L, Foster M, Tallbull G, Spicer PLewis CM. (2015) Gut Microbiome Diversity among Cheyenne and Arapaho Individuals from Western Oklahoma. Current Biology, doi: http://dx.doi.org/10.1016/j.cub.2015.10.060.

Warinner C, Lewis CM. (2015) Microbiome and health in past and present human populations. American Anthropologist, doi:10.1111/aman.12367.

Obregon-Tito ATito R, Metcalf J, Sankaranarayanan K, Clemente J, Ursell L, Xu Z, Van Treuren W, Knight R, Gaffney P, Spicer PLawson P, Marin-Reyes L, Trujillo-Villarroel O, Foster M, Guija-Poma E, Troncoso-Corzo L, Warinner COzga ALewis CM. (2015) Subsistence strategies in traditional societies distinguish gut microbiomes. Nature Communications 6, 6505.

Patel NTito RObregon-Tito AO’Neal L, Trujillo-Villaroel O, Marin-Reyes L, Troncoso-Corzo L, Guija-Poma E, Hamada M, Uchino Y, Lewis CMLawson PA* (2015) Ezakiella peruensis gen. nov., sp. nov. isolated from human fecal sample from a coastal traditional community in Peru. Anaerobe 32, 43-48.

Warinner C, Speller C, Collins MJ, Lewis CM* (2015) Ancient Human Microbiomes. Journal of Human Evolution 79, 125-136. http://dx.doi.org/10.1016/j.jhevol.2014.10.016

Cleeland LM, M Reichard, RY Tito, K Reinhard, CM Lewis Jr. (2013) Clarifying Prehistoric Parasitism from a Complementary Morphological and Molecular ApproachJournal of Archaeological Science. 40(7): 3060–3066. PMID: 23645967.

Tito, RY, D Knights, J Metcalf, AJ Obregon-TitoL Cleeland, F Najar, B Roe, K Reinhard, K Sobolik, S Belknap, M Foster, P Spicer, R Knight, CM Lewis, Jr, (2012), Insights from Characterizing Extinct Human Gut MicrobiomesPLoS ONE 7(12): e51146. PMCID: PMC3521025.

Tito RY, S Macmil, G Wiley, F Najar, L Cleeland, C Qu, P Wang, F Romagne, S Leonard, AJ Ruiz, K Reinhard, BA Roe, CM Lewis, (2008), Phylotyping and Functional Analysis of Two Ancient Human MicrobiomesPLoS ONE 3(11):e3703. PMCID: PMC2577302.

CALCULUS

Evolution and Ecology of the Human Oral Microbiome

The oral microbiome, and dental plaque in particular, holds a special place in the history of microbiology. The first undisputed description of bacteria appears in a letter written by Antoni van Leeuwenhoek to the Royal Society of London in 1683 in which he describes ‘very many small living Animals, which moved themselves very extravagantly’ within his dental plaque. Attempting in vain to count them, he noted, ‘The number of these animals in the scurf of mans [sic] Teeth, are so many that I believe they exceed the number of Men in a kingdom.’ Van Leeuwenhoek’s analogy is, if anything, understated. The average healthy person carries on the surface of their teeth nearly as many bacteria as there are humans on the Earth, and every day each of us swallows an average of 80 billion bacteria in our saliva. The human oral cavity is thus more than a kingdom, it is an entire world unto itself.

The oral microbiome is the second largest human-associated microbial community, after the gut, and oral microbes exhibit an astounding diversity of predicted protein functions compared with other body sites. Unlike other microbiomes, the oral microbiome will cause dental disease in a majority of people during their lifetime, and oral bacteria have been implicated in extra-oral diseases, including cardiovascular disease, respiratory illness, and sexually-transmitted infections. However, few studies have conducted basic research on the natural variation and diversity of the human oral microbiome, and as a result little is known about its origins and evolutionary ecology.

Focusing on a set of extraordinary archaeological dental calculus samples, this project seeks to reconstruct the evolutionary history of the human oral microbiome by tracing major taxonomic and functional shifts since the human chimpanzee split.

Publications resulting thus far from this project include:

Warinner C, Speller C, Collins MJ, Lewis CM* (2015) Ancient Human Microbiomes. Journal of Human Evolution 79, 125-136. http://dx.doi.org/10.1016/j.jhevol.2014.10.016

Warinner C*, Speller C, Collins MJ (2014) A New Era in Paleomicrobiology: Prospects for Ancient Dental Calculus as a Long-Term Record of the Human Oral Microbiome. Philosophical Transactions of the Royal Society B 370: 20130376. http://dx.doi.org/10.1098/rstb.2013.0376

Warinner C*, Rodrigues JFM, Vyas R, Trachsel C, Shved N, Grossmann J, Radini A, Hancock Y, Tito RY, Fiddyment S, Speller C, Hendy J, Charlton S, Luder HU, Salazar-García DC, Eppler E, Seiler R, Hansen L, Samaniego Castruita JA, Barkow-Oesterreicher S, Teoh KY, Kelstrup C, Olsen JV, Nanni P, Kawai T, Willerslev E, von Mering C, Lewis, Jr. CM, Collins MJ, Gilbert MTP, Rühli F, Cappellini E* (2014). Pathogens and host immunity in the ancient human oral cavity. Nature Genetics 46(4):336-344. doi:10.1038/ng.2906.

MILK

Dairying and Dietary Adaptive Evolution in Ancient Europe

Milk is a major food of global economic importance. Humans have exploited animal milk as a food resource for at least 8500 years, and in order to overcome milk indigestibility during adulthood many populations have developed cultural practices to reduce the lactose content of milk. Additionally, some populations have evolved lactase persistence (LP), a genetic trait that enables continued lactose digestion after infancy. Today, these adaptations are most evident in Eurasia and East Africa, but the origins, spread, and scale of dairying remain poorly understood. Current lines of evidence, such as lipid isotopic ratios of pottery residues, faunal mortality profiles, and LP allele frequencies, imply a complex history of dairying at the level of populations. However, in order to understand how, where, and when humans consumed milk products, it is necessary to link evidence of consumption directly to individuals and their dairy livestock.

Using protein tandem mass spectrometry, our research focuses on the direct detection of  the milk whey protein β-lactoglobulin (BLG) in prehistoric human dental calculus. BLG is a species-specific biomarker of dairy consumption, and thus far we have identified individuals consuming cattle, sheep, and goat milk products as far back as the Bronze Age. Applying this technique to more recent populations, we have also been able to document and confirm major historical dietary shifts. For example, when we applied this method to Greenland’s medieval Norse colonies, a population known for its extreme reliance on dairy products, we observed a decline of this biomarker in the dental calculus of Norse Greenlanders consistent with diminished access to milk products leading up to the abandonment of the Norse Greenland colonies in the second half of the 15th century CE.

We are now expanding this research to Neolithic and Bronze Age populations in the Near East and Europe in order to directly test and refine multiple hypotheses regarding the origins and spread of Neolithic dairying, and to resolve ongoing debates about the scale of dairying before the rise of genetic LP and the relative importance of sheep, goats, and cattle in early dairying economies.

Publications resulting thus far from this project include:

Warinner C*, Hendy J, Speller C, Cappellini E, Fischer R, Trachsel C, Arneborg J, Lynnerup N, Craig OE, Swallow DM, Fotakis A, Christensen RJ, Olsen J, Liebert A, Montalva N, Fiddyment S, Mackie M, Canci A, Bouwman A, Rühli F, Gilbert MTP, Collins MJ* (2014) Direct Evidence of Milk Consumption from Ancient Human Dental Calculus. Scientific Reports 4, 7104. doi:10.1038/srep07104.

Kruettli A, Bouwman A, Akguel G, Della Casa P, Ruehli F, Warinner C* (2014). Ancient DNA analysis reveals high frequency of European lactase persistence allele (T-13910) in medieval Central Europe. PLoS ONE 9(1), e86251.

Research Partnerships with External Projects

MUSTANG

Human Migration and Adaptation in Extreme Environments

Project PI: Mark Aldenderfer

Since prehistory, the Himalayan mountain range has presented a formidable barrier to population migration, while at the same time its transverse valleys have long served as conduits for trade and exchange. Yet, despite the long-term economic and cultural importance of Himalayan trade routes, little is known about the region’s peopling and early population history. Focusing on the Annapurna Conservation Area (ACA) of Nepal, this project seeks to reconstruct the population history of the Himalayan arc by generating genome-wide genetic data from prehistoric ACA individuals dating to three distinct cultural periods ranging in time from the earliest known human settlements (ca. 3150 BP) to the establishment of the Tibetan Empire (ca. 1250 BP). Considering the pivotal role played by the Himalayan high transverse valleys in connecting far-flung Eurasian populations, as well as the environmental challenges the Himalayas impose on their inhabitants (e.g., extreme cold stress and hypoxia), our study has deep implications for reconstructing human prehistoric migration history, understanding biocultural adaptation to local environments, and informing future genetic archaeology studies.

NEXUS

NEXUS 1492: Biomolecular analyses of skeletal remains in the circum-Caribbean across the historical divide (A.D. 1000-1800)

Project PI: Corinne Hofman

Graduate Student: Kirsten Ziesemer

Beginning in A.D. 1492, the circum-Caribbean was the locus of the first large-scale encounters between the Old and New Worlds, bringing together populations of diverse geographical origins. Yet, even before European arrival the circum-Caribbean was already an inter-connected region, with intra- and inter-island mobility. Consequently, there is great interest in studying the long-term population history of the circum-Caribbean. However, due to the demographic impact and disease history of European colonization and subsequent admixture with both Europeans and Africans, it is very difficult to obtain genetic information on the indigenous inhabitants of the Caribbean from present-day populations. Ancient DNA (aDNA) techniques present a powerful alternative method for recovering genetic information from the indigenous inhabitants of the Caribbean before, during, and after the European contact.

This project focuses on the characterization of aDNA from skeletal and dental calculus remains  in order to better understand human migration and health in the ancient Caribbean. In pursuit of these questions, we also explore technical challenges associated with the successful recovery of aDNA from warm climates, which are characterized by high rates of biomolecular degradation.

Publications resulting thus far from this project include:

Ziesemer KA, Mann AESankaranarayanan K, Schroeder H, Ozga AT, Brandt BW, Zaura E, Waters-Rist A, Hoogland M, Salazar Garcia DC, Aldenderfer M, Speller C, Hendy J, Weston DA, MacDonald SJ, Thomas GH, Collins MJ, Lewis CM, Hofman C, Warinner C*. Intrinsic challenges in ancient microbiome reconstruction using 16S rRNA gene amplification. Scientific Reports 5, 16498. doi: 10.1038/srep16498.