University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2019 Effects Of Diet And Parasites On The Gut Microbiota Of Diverse Sub-Saharan Africans Meagan Rubel University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Biological and Physical Anthropology Commons, Genetics Commons, and the Microbiology Commons Recommended Citation Rubel, Meagan, "Effects Of Diet And Parasites On The Gut Microbiota Of Diverse Sub-Saharan Africans" (2019). Publicly Accessible Penn Dissertations. 3406. https://repository.upenn.edu/edissertations/3406 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/3406 For more information, please contact [email protected]. Effects Of Diet And Parasites On The Gut Microbiota Of Diverse Sub-Saharan Africans Abstract ABSTRACT EFFECTS OF DIET AND PARASITES ON THE GUT MICROBIOTA OF DIVERSE SUB-SAHARAN AFRICANS Meagan A. Rubel Sarah A. Tishkoff Contemporary African populations possess myriad genetic and phenotypic adaptations to diverse diets, varying climates, and infectious diseases. Most microbiome studies to date have focused on primarily European and Asian populations in urban, industrialized settings. By comparison, relatively little is known about traditional African gut microbiomes, and the range of variation they contain. Many African populations are undergoing substantial changes because of rapid globalization, easier access to hygienic resources and medications, shifts away from traditional lifestyle, and increased exposure to processed diets high in sugars and fats. By characterizing microbiome variation among sub-Saharan African populations using metagenomic sequencing, we can better understand differential response to diseases and environmental factors in producing physiological adaptations. Furthermore, by extending microbiome sampling across a range of traditional African populations in multiple countries, it may be possible to trace subsistence transition with changes in settlement and diet, and interrogate how these are shaped by industrialization. In this dissertation, I describe the gut microbiomes of populations practicing agropastoralism, hunting and gathering, and pastoralism in three African countries: Botswana, Cameroon, and Tanzania. To do this, I used amplicon and shotgun sequencing to characterize microbial genomes and annotate their functions. I combined this microbial data with extensive phenotype and ethnographic data. With this dataset, I detected gut microbial taxa associated with subsistence strategy, sex, geography, and host genetics. I demonstrated that the degree of industrialization in these populations correlated with enrichment of functional pathways involved in the metabolism of xenobiotics and industrial pollutants. Moreover, I found that the gut microbiome has no association with HIV infection, but is highly predictive of multiple gastroenteric parasite infections within Cameroonians. Parasite infection and microbiome composition were, in turn, associated with Th-2 proinflammatory cytokines that are produced during helminthiasis. My research captures microbiota and taxa that are rare or absent from microbiomes of industrialized populations and expands the definition of normal ariationv within the human gut microbiome. My dissertation identifies multiple factors affecting microbiome composition and works towards generating a more holistic interpretation of the structure and function of human gut microbiota, and their potential associations with human physiology and adaptation. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Anthropology First Advisor Sarah A. Tishkoff Second Advisor Theodore G. Schurr Keywords Africa, Helminths, Hunter-Gatherer, industrialization, Microbiome, parasites Subject Categories Biological and Physical Anthropology | Genetics | Microbiology This dissertation is available at ScholarlyCommons: https://repository.upenn.edu/edissertations/3406 EFFECTS OF DIET AND PARASITES ON THE GUT MICROBIOTA OF DIVERSE SUB-SAHARAN AFRICANS Meagan A. Rubel A DISSERTATION in Anthropology Presented to the Faculties of the University of Pennsylvania in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy 2019 Supervisor of Dissertation Co-Supervisor of Dissertation _______________________ _______________________ Sarah A. Tishkoff, Ph.D., Theodore G. Schurr, Ph.D., Professor of Genetics and Biology Professor of Anthropology Graduate Group Chairperson _______________________ Theodore G. Schurr, Professor of Anthropology Dissertation Committee Frederic D. Bushman, Ph.D., Professor of Microbiology Daniel P. Beiting, Ph.D., Assistant Professor of Pathobiology EFFECTS OF DIET AND PARASITES ON THE GUT MICROBIOTA OF DIVERSE SUB-SAHARAN AFRICANS COPYRIGHT 2019 Meagan Amelia Rubel For my Dad, who was the first one to show me the wonder of the natural world. 1955-2010 ACKNOWLEDGMENTS It takes a village, as they say. For an anthropologist studying the gut microbiome with equal measures of parasitology, microbiology, and human genetics thrown in, it has taken a figurative city. First, I owe a debt of gratitude to the many African people who gave time, samples, and energy to this study. Fieldwork was a humbling experience that I am honored to have had. It indelibly changed my research and pedagogy for the better, it humanized my work in a way that no other experience would have, and it let me forge some amazing friendships. This work would also not be possible without the mentorship of Sarah Tishkoff and Rick Bushman. Sarah allowed me the scientific freedom to pursue an unconventional project in her lab, opened many collaborative doors for my research, and supported me through countless grants, papers, presentations, and international fieldwork. She has been a wellspring of advice throughout my graduate career, and her confidence in my abilities and willingness to probe my assumptions has made me into a more meticulous scientist. Rick Bushman’s acumen of technical and experimental knowledge on the microbiome gave me the scientific tools to realize this dissertation. I have greatly appreciated his mentorship, his unwavering commitment to conducting rigorous science, and the energy he’s invested in seeing me cross the finish line. Dan Beiting was there in the eleventh hour to offer advice, reagents, computational help, creative solutions, or the pep talk that I needed to overcome obstacles along the way. Tad Schurr paved the path for me to attend the University of Pennsylvania and has chaperoned my scholarship since I started here; his guidance has been essential for my development. iv Faculty outside my dissertation committee generously gave time to answer my questions and discuss my research progress. No matter how many projects he was juggling, Kyle Bittinger always made time to offer project advice- he demystified the command line and inspired me with the confidence to begin building my own code. I am indebted to the many talented researchers at the PennCHoP Microbiome Program, especially Ceylan Tanes and Lisa Mattei, for technical assistance throughout this research. My academic sister, Stephanie Schnorr, made anything difficult both endurable and humorous. Our discussions about humans as holobionts have been and continue to be some of the most thought-provoking discussions about human evolution that I’ve had. Janet Monge and Babette Zemel have been in the wings to champion my cause and talk biological anthropology. Chris Hunter helped me hone my background in parasitology and, along with Omar Harb and Lilach Sheiner, let me TA the Middle Eastern Biology of Parasitism course, which proved to be one of the most personally rewarding endeavors in my academic career thus far. I thank our African collaborators: Thomas Nymabo, Alfred Njamnshi, Charles Fokunang, Gaonyadiwe George Mokone, and Sununguko Wata Mpoloka were instrumental to obtaining permissions and samples in their respective countries, and have been enthusiastic supporters of my research. I have never met a more intellectually engaging and collaborative group of peers in my life than in graduate school. I am grateful for the camaraderie of my fellow Anthropology graduate students: to my cohort mates, Katherine Culver, Negar Razavi, Utpal Sandesara, and Nick Iacobelli; my fellow bioanthros Volney Friedrich, Sam Larson, Andrea Spence- Aizenberg, Maggie Corley, Raquel Fleskes, Elizabeth Oakley, Clare Super, and v Alexandra Kralick; and Tom Hardy, Kevin Burke, Noam Osband, Kyle Olson, Paul Mitchell, Maddie Boyer, Joanne Baron, Whit Schroeder, Susannah Fishman, Diego Arispe-Bazan, Tiffany Cain, Nooshin Samimi, and Paul Babb- thank you for your brilliance, and your kindness. You all challenged me to situate my work in anthropology, and my research has been all the better for it. The friends I made in the MVP and Genetics programs, including Marco Trazzino, Derek Kelly, Rachel Kember, Matt Hansen, Nick Crawford, Devin Fisher, Shannon Barbour, Eric Mbunwe, Amy Davis, Kelsey Johnson, and Katie Siewert, have been veritable troves of project ideas and morale. Jaanki Dave was a pleasure to mentor during her summer rotation, and she spent months with me, Elizabeth Loy, and Alexa Avitto in the wet lab trenches, extracting thousands of samples for these projects. The collaborative work we’ve done together, which goes beyond what’s presented in this dissertation, was a genuine pleasure to be a part of. I also want to express my