Research

Our research has two broad goals. The first is to better understand the relationships between host genetic variation and variation in the microbiome. We aim to identify relationships between host genetics and aspects of the host microbiome that can point to novel mechanisms underlying host control of the microbiome. To answer this question we work in human and maize genetics. The second goal is to better understand how interactions between host immunity and microbiota in the mammalian gut result in inflammation, and how adaptive immunity can be utilized to reshape pathogenic microbiomes. We study microbiota-immune interactions using mouse models and gnotobiotics. Projects in the lab fall into these categories:

  1. How the composition of the microbiome relates to host genetic variation. We study this in humans and in maize. In humans, we study gentoyped twins to evaluate the heritability of the gut microbiome and to identify specific alleles that are associated with components of the microbiome. We also study gene copy number of key human genes related to diet processing in relation to the composition, function, and phenotype effects of the microbiome. Results will guide us to novel pathways for host-microbial interactions and novel therapies tailored to an individual’s genetic make-up.
  2. How immunity shapes microbiome population structure and gene expression in the gut. We work on microbiome-host immunity interactions in a mouse model for metabolic syndrome, in which the syndrome is transmissible by the gut microbiota. This work led us to the discover that antibodies secreted into the gut can signal to motile microbiota to cease their motility in a process that may be fundamental to gut homeostasis (Cullender, Cell Host Microbe, 2012). We have recently established a gnotobiotic colony for testing the role of specific microbiota and their gene products in driving the phenotype.
  3. The role of the gut microbiota in metabolism during pregnancy. We have recently described a remodeling of the gut microbiota during pregnancy that can impact host metabolism (Koren, Cell, 2012). Pregnancy brings about metabolic changes in the mother that are similar to metabolic syndrome, but in the context of pregnancy these changes are thought to be beneficial. We showed that the microbiota are altered in pregnancy and may drive these metabolic changes. Our current work explores whether gestational diabetes may also be driven by aberrant host-microbial interactions, which may then present a therapeutic target for this dangerous condition.
  4. Rhizosphere microbiome research. Plants and animals last shared a common ancestor 1 billion years ago. Although they diverged on their own evolutionary trajectories, one aspect of the environment that both had to contend with is microbes. As in mammals, the question of whether naturally occurring host genetic variation was related to microbiome variation was wide open. We worked with Jeff Dangl (HHMI, UNC), Ed Buckler (USDA, Cornell), and Susannah Tringe (JGI) to answer this question in one of the most agronomically important crops: Maize. In an initial study, we profiled the maize root microbiome under field conditions in five fields in three states, and sampled roots from 27 genotypes of maize planted in replicated block design over 15 weeks during the growing season. Our initial results of the rhizosphere microbiome at flowering showed a slight but significant plant genotype effect while controlling for environmental effects (Peiffer, PNAS, 2013). We are in the process of analyzing the full time series (~4,400 samples sequenced by MiSeq). The ultimate goal for the field is to incorporate beneficial host-microbiome interactions into breeding schemes to maximize plant productivity while reducing reliance on fertilizers such as phosphates and other intensive practices.
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