Research Areas

We manage a diverse, interdisciplinary research portfolio that broadly focus on the topic areas described below. These projects often benefit from a rich array of collaborators and facilities.

The Microbiome’s Connection to Health and Behavior

Ultimately, we seek to advance human and animal welfare by leveraging our knowledge of how the microbiome impacts health and behavior. To get there, we must first define the components of the gut microbiome that link to and impact health. To do so, we apply systems biology techniques that statistically link features of the microbiome, such as specific taxa, the genes they carry or the metabolites they produce, to physiological traits of their host. Our research in this area includes studies in varying vertebrate models and human populations and evaluates diverse aspects of physiology, including cardiometabolic state, immune regulation, and pathogen burden, as well as behavior, ranging from aggression in dogs to mental health in children. We are increasingly following up on the leads produced by this work to discern which aspects of the gut microbiome influence health.

Relevant Publications

  • Armour C, Nayfach S, Pollard KP, Sharpton TJ. (2019) A Metagenomic Meta-Analysis Reveals Functional Signatures of Health and Disease in the Human Gut Microbiome. mSystems. 4:4, e00331-18.
  • Raber J, Yamazaki J, Torres ERS, Kirchoff N, Stagaman K, Sharpton TJ, Turker MS, Kronenberg A (2019). Combined Effects of Three High-Energy Charged Particle Beams Important for Space Flight on Brain, Behavioral and Cognitive Endpoints in B6D2F1 Female and Male Mice. Frontiers in Physiology. 10:179. doi: 10.3389/fphys.2019.00179
  • Flannery J, Callaghan B, Sharpton TJ, Fisher P, Pfeifer J. (2019) Adolescence: the next frontier in gut-brain-microbiome-axis communication? Developmental Psychobiology. 61:783-795. doi: 10.1002/dev.21822
  • Gaulke CA, Martins ML, Watral V, Humphreys IR, Spagnoli ST, Kent ML, Sharpton TJ. (2019) A Longitudinal Assessment of Host-Microbe-Parasite Interactions Resolves the Zebrafish Gut Microbiome’s Link to Pseudocapillaria tomentosa Infection and Pathology. Microbiome. 7:10. doi: https://doi.org/10.1186/s40168-019-0622-9
  • Kirchoff N, Udell M, Sharpton TJ. (2019) The gut microbiome correlates with conspecific aggression in a small population of rescued dogs (Canis familiaris). PeerJ. 7:e6103. doi: 10.7717/peerj.6103
  • Gaulke C, Sharpton TJ. (2018). Ethnicity and geography influence the human gut microbiome. Nature Medicine. 24, 1495-1496
  • Sharpton TJ$, Lyalina S$, Luong J, Pham J, Deal EM, Armour C, Gaulke C, Sanjabi S, Pollard KS. (2017) Development of Inflammatory Bowel disease is Linked to a Longitudinal Restructuring of the Gut Metagenome in Mice. mSystems. doi: 10.1128/mSystems.00036-17
  • Conley MN, Wong CP, Duyck K, Hord N, Ho E, Sharpton TJ. (2016) Aging and serum MCP-1 are associated with gut microbiome composition in a murine model. PeerJ. 4:e1854
  • Finucane M, Sharpton TJ, Laurant T, Pollard KS (2014) A taxonomic signature of obesity in the microbiome? Getting to the guts of the matter. PLOS ONE. 9(1): e84689. PMCID: PMC3885756$

The Impact of Exogenous Factors on the Gut Microbiome

Exposure to various environmental conditions, especially through our diet, can disrupt the gut microbiome’s contribution to health. To safeguard against microbiome-related diseases and inform public health policy, we must define how environmental exposure affects the microbiome. We pursue this definition by through a variety of means, but especially by developing zebrafish as an experimental model that enables rapid screening of how different nutrients, chemicals, or pathogens impact the gut microbiome. For example, we showed that Triclosan, an antibiotic commonly added to household products, perturbs the adult zebrafish gut microbiome. We subsequently innovated a passive microbiome sampling strategy in zebrafish that we use to measure how the microbiome changes throughout the course of various exposures, including persistant organic pollutants and intestinal parasites. We are currently using these innovations in zebrafish alongside our ability to produce germ-free fish to quanitfy the microbiome’s role in the detoxification of environmental chemicals. We also used other animals to study additional components of the exposure-microbiome axis, including mixed beam radiation, abiotic parameters, and neurotoxin exposure. Our reserach in this area also advances our understanding of how the diet impacts the gut microbiome, such as our finding of how dietary zinc deficiency sensitizes the microbiome to arsenic exposure.

Relevant Publications

  • Raber J, Yamazaki J, Torres ERS, Kirchoff N, Stagaman K, Sharpton TJ, Turker MS, Kronenberg A (2019). Combined Effects of Three High-Energy Charged Particle Beams Important for Space Flight on Brain, Behavioral and Cognitive Endpoints in B6D2F1 Female and Male Mice. Frontiers in Physiology. 10:179. doi: 10.3389/fphys.2019.00179
  • Gaulke CA, Rolshoven J, Wong CP, Hudson LG, Ho E, Sharpton TJ. (2018) An investigation of the combinatorial effects of marginal zinc deficiency and environmentally relevant concentrations of arsenic on the microbiome. mSphere. 3(6). doi: 10.1128/mSphere.00521-18.
  • Torres ERS, Akinyeke T, Stagaman K, Duvoisin RM, Meshul CK, Sharpton TJ, Raber J. (2018). Effects of sub-chronic MPTP exposure on behavioral and cognitive performance of wild-type and mGlu8 knockout female and male mice. Frontiers in Neuroscience. 12:140. doi: 10.3389/fnbeh.2018.00140.
  • Wang L, Shantz AA, Payet JP, Sharpton TJ, Foster A, Burkepile DE, Vega Thurber R (2018). Corals and Their Microbiomes are Differentially Affected by Exposure to Elevated Nutrients and a Natural Thermal Anomaly. Frontiers in Marine Science. https://doi.org/10.3389/fmars.2018.00101
  • Gaulke CA, Barton CL, Proffitt S, Tanguay RL, Sharpton TJ. (2016) Triclosan Exposure is Associated with Rapid Restructuring of the Gut Microbiome in Adult Zebrafish. PLOS ONE. 11(5): e0154632

Emergent work the lab considers that if the microbiome matters to health, then it may also impact animal ecology and evolution. Our studies across diverse vertebrate species revealed common links between the microbiome and its host. We postulate that these patterns emerge because vertebrate survival in nature depends on key gut microbes. Using new approaches we innovated, we compared gut microbiome samples across mammalian species to discovered that mammals carry unexpectedly common gut bacteria, many of which evolved in concert with mammal. These findings indicate that mammalian evolution may depend upon these microbes, though further study is needed to discern their effect. We also collaborate with many wildlife ecologists through collaborative projects designed to determine how the microbiome links to and possibly influences vertebrate ecology and fitness. Ultimately, we hope to uncover microbes that indicate wildlife health thereby aiding conservation efforts. This work may also transform our understanding of vertebrate evolution.

Relevant Publications

  • Gaulke CA$, Arnold HK$, Humphreys IR, Kembel SW, O’Dwyer JP, Sharpton TJ. (2018) Ecophylogenetics Clarifies the Conservation of Gut Bacteria Across Mammals. mBio. 9:e01348-18. https://doi.org/10.1128/mBio.01348-18
  • Sharpton TJ. (2018) Role of the Gut Microbiome in Vertebrate Evolution. mSystems. 3 (2): e00174-17. DOI: 10.1128/mSystems.00174-17.

Microbiome and Metagenome Data Analytics

The complexity of microbiome data often hinders discovery. We play a central role in equipping investigators with an analytical toolkit that links microbiomes to health. For example, we defined best practices for imputing a microbiome’s functions from metagenomic data and produced software that implements our approach, introduced statistical methodology to connect changes in the microbiome to changes in health, and integrated thousands of gut metagenome samples to resolve microbiome functions that robustly predict specific diseases. We have also developed new microbiome data visualization tools as well as theoretical frameworks for understanding microbial community ecology and evolution.

Many of our current efforts in microbiome data analytics involve generating methodology to unbiasedly infer microbe-microbe interactions from DNA sequence data, statistically integrate high-dimensional data sets, and impute key traits of the microbiome using machine learning approaches.

The software and data resources that result from our efforts are generated under open access lisences.

Relevant Publications

  • Jiang D, Armour CR, Hu C, Mei M, Tian C, Sharpton TJ, Jiang Y. (In print) Microbiome Multi-Omics Network Analysis: Statistical Considerations, Limitations, and Opportunities. Frontiers in Genetics.
  • Armour C, Nayfach S, Pollard KP, Sharpton TJ. (2019) A Metagenomic Meta-Analysis Reveals Functional Signatures of Health and Disease in the Human Gut Microbiome. mSystems. 4:4, e00331-18.
  • Gaulke CA$, Arnold HK$, Humphreys IR, Kembel SW, O’Dwyer JP, Sharpton TJ. (2018) Ecophylogenetics Clarifies the Conservation of Gut Bacteria Across Mammals. mBio. 9:e01348-18. https://doi.org/10.1128/mBio.01348-18
  • Sharpton TJ$, Lyalina S$, Luong J, Pham J, Deal EM, Armour C, Gaulke C, Sanjabi S, Pollard KS. (2017) Development of Inflammatory Bowel disease is Linked to a Longitudinal Restructuring of the Gut Metagenome in Mice. mSystems. doi: 10.1128/mSystems.00036-17
  • Foster Z, Sharpton TJ, Grunwald N. (2017) Metacoder: An R package for visualization and manipulation of community taxonomic diversity data. PLOS Computational Biology. 13(2): e1005404. https://doi.org/10.1371/journal.pcbi.100540
  • Nayfach S, Bradley PH, Wyman SK, Laurent TJ, Williams A, Eisen JA, Pollard KS, Sharpton TJ. (2015) Automated and accurate estimate of gene family abundance from shotgun metagenomes. PLOS Computational Biology. 11(11):e100457
  • Sharpton TJ. (2014) An Introduction to the Analysis of Shotgun Metagenomic Data. Frontiers in Plant Genetics and Genomics. 5(209) PMCID: PMC4059276.
  • Kidd JM$, Sharpton TJ$, Norman PJ, Carpenter M, Sikora M, Gignoux CR, Gorgani NN, Agilent Technologies, Pollard KS, Parham P, Feldman MW, Wall J, Bustamante CD, Henn BM. (2014) Exome Capture from Saliva Produces High Quality Genomic and Metagenomic Data. BMC Genomics. 15(262). PMCID: PMC4051168
  • Finucane M, Sharpton TJ, Laurant T, Pollard KS (2014) A taxonomic signature of obesity in the microbiome? Getting to the guts of the matter. PLOS ONE. 9(1): e84689. PMCID: PMC3885756$
  • Sharpton TJ$, Jospin G$, Wu D, Langille MG, Pollard KS, Eisen JA (2012). Sifting through genomes with iterative-sequence clustering produces a large, phylogenetically diverse protein-family resource. BMC Bioinformatics. 13(1): 264. PMCID: PMC3481395
  • Sharpton TJ, Riesenfeld SJ, Kembel SW, Ladau J, O’Dwyer JP, Green JL, Eisen JA, Pollard KS (2011). PhylOTU: a high-throughput procedure quantifies microbial community diversity and resolves novel taxa from metagenomic data. PLOS Computational Biology. 7(1): e1001061. PMCID: PMC3024254