As a part of our Microbiome research interview series, we spoke with Dr. Aaron Ericsson. He is Director of the University of Missouri Metagenomics Center and an Assistant Professor in the Department of Veterinary Pathobiology at the University of Missouri. His research comprises several different projects, including:
• A K01-funded study investigating the influence of different complex gut microbial profiles and specific taxa on host susceptibility to colorectal cancer.
• Investigation of the influence of reducing (or electron-donating) microbes in the gut and their influence on the development of the immune system.
• Investigation of the respiratory microbiome during acute and chronic inflammatory conditions.
He has published extensively on host-associated microbial communities in the gut and other tissues in a myriad of host species including rodents, dogs, cats, cattle, horses, zebrafish and zoo animals.
What is your background and how did you become interested in science?
My undergraduate degree is actually in English and after finishing that, I became a partner in a commercial painting company. As that became increasingly onerous, I began looking for more enjoyable or stimulating work and ended up working at a large animal shelter, cleaning kennels and cages and helping with the animals. I loved working with animals and a year later, I was working as a veterinary technician in an extremely busy animal hospital in St. Louis. This was my first exposure to science, in the context of animal health and veterinary medicine, and I was instantly hooked. A handful of other technicians were working on applications to vet school and within a few months, I had enrolled in the University of Missouri – St. Louis (UMSL) to fulfill all of the science courses required for application to the MU College of Veterinary Medicine (CVM). Following acceptance to the CVM, I began my studies with the full intention of becoming a small animal clinical practitioner and had little appreciation for the role of DVMs in biomedical research. During an immunology lecture, however, the professor (Dr. Craig Franklin) made reference to comparative medicine and described the concept we now refer to as “one health”. A light bulb went on, and I realized shortly thereafter that I’d found my passion. I took every opportunity I could find to gain exposure to the field and following completion of my DVM, continued my training with a three-year residency in Comparative Medicine and a PhD in Veterinary Pathobiology. Since that time, I’ve served as lead scientist for microbiome research for the NIH-funded Mutant Mouse Resource and Research Center (MMRRC, directed by Dr. Craig Franklin) at MU and the Rat Resource and Research Center (RRRC, directed by Dr. Elizabeth Bryda), Director of the MU Metagenomics Center (MUMC), and a faculty member in the Department of Veterinary Pathobiology.
Can you provide a summary of the project funded by the K01 Award?
My K01-funded research centers on the Smad3 knockout mouse model of colorectal cancer (CRC). The neoplastic process is initiated in this model via oral inoculation at weaning with Helicobacter bilis or H. hepaticus, provocateurs of immune responses against other resident microbes in the gut. Notably, while Smad3-/- mice free of Helicobacter spp. do not develop CRC, only a portion of mice (25% to 75%) colonized at weaning with these Helicobacter spp. will progress to CRC, despite shared genetics and environment. Considering the unstable and varied composition of the gut microbiota (GM) in weanling mice, we hypothesize that the differential susceptibility to CRC is due to differences in the GM during the transient dysbiosis occurring in response to Helicobacter inoculation. Preliminary data have revealed a marked proliferation of microbes in the family Enterobacteriaceae which co-occurs with the transient expansion of Helicobacter shortly after inoculation (day 4 to day 7). This temporary dysbiosis wherein Helicobacter and Enterobacteriaceae comprise as much as 50% of the bacterial DNA present in feces is almost completely abrogated by the presence of segmented filamentous bacteria (SFB), a non-pathogenic taxon residing exclusively in the ileum and capable of inducing non-specific IgA and robust TH17 immune responses. Interestingly, while neither the presence of SFB or abundance of Enterobacteriaceae individually correlate with disease incidence, the presence of SFB stabilizes the microbiota following Helicobacter inoculation and prevents the proliferation of Enterobacteriaceae. Ongoing studies using separately rederived colonies of Smad3-deficient mice harboring high and low richness microbiota suggest that the increased abundance of Enterobacteriaceae prior to inoculation with Helicobacter spp. predisposes mice to an increased incidence of CRC.
Are you working on any other new projects in the field of microbiome research? If so can you tell us a little about these?
We have several other areas of ongoing research related to the gut microbiota. Through the MMRRC and RRRC, we’ve performed a large series of experiments designed to determine the influence of a broad range of environmental and animal husbandry-related variables on the gut microbiota of research mice and rats. We believe that differences in the microbiota resulting from such seemingly benign factors as bedding type or method of water purification may be at the root of phenotypic differences in commonly used research models and poor reproducibility of pre-clinical data.
Our lab is also interested in the signals governing recruitment of lymphocytes to the gut during development (both in utero and post-natal) and how differential recruitment of lymphocytes during development of the immune system affects susceptibility to inflammatory conditions in later life. Specifically, we focus on a group of bacteria known as exoelectrogens, which are capable of using non-oxygen molecules as terminal electron acceptors in the electron transport chain (i.e., anaerobic respiration). Of note, lymphocytes will migrate toward an electrical current, suggesting that electron gradients may play a role in non-specific migration of lymphocytes to the gut lamina propria during development. This so-called “physiological inflammation” is associated with differential susceptibility to both intestinal and systemic inflammatory conditions induced in adult animals. Current studies are evaluating the dependence of exoelectrogeninduced lymphocyte recruitment on specific membrane cytochromes (i.e., the proteins responsible for extracellular transport of electrons) and host electron acceptors (e.g., sulfated mucin proteins).
Lastly, I collaborate with clinical veterinarians in several different projects examining the microbiota of companion animals, often working with non-intuitive samples such as bronchoalveolar lavage fluid. Perhaps not surprisingly, the lungs of cats and dogs harbor relatively uniform, low biomass microbial communities and one of the big questions in veterinary (and human) health is whether those endemic bacterial species are performing any beneficial functions for host health, such as colonization resistance.
Can you describe a typical day for you in the lab?
Unfortunately, I do not spend much time in the lab performing bench-top work; rather, the bulk of my time is spent in the office analyzing data, writing manuscript and grant proposals, reviewing manuscripts and interacting with clients and collaborators. As a graduate student, I always wished I had more time to read and write; as a faculty member, the lab now seems more attractive! When I am in the lab, I’m usually interacting with students or staff to make sure everything is running as smoothly as possible.
What do you find most interesting about your project? What is the most interesting or surprising result you have found?
One of our most interesting, and surprising, findings was the consistent difference in “current production” in microbial fuel cells inoculated with mouse feces from different vendors. These initial observations, reproduced repeatedly in multiple genetic backgrounds of mice, spurred our current investigations into exoelectrogenic bacteria and their influence on host immunity.
What are the important benefits of your research to science/human or animal health?
We’ve performed several basic studies treating the gut microbiota (GM) as both the dependent and independent variable in mice, with the goal of identifying practices that significantly change the composition of inbred mouse GM, and changes in the GM that lead to downstream phenotypic changes in mouse models of disease. The ultimate goal of these projects is to document such relationships and highlight their potential impact on the reproducibility of biomedical research. More specifically, the focus of my research is how characteristics of the GM in early life influence the reactivity and function of the host immune system and susceptibility to immune-mediated and infectious diseases later in life. Ideally, this work will lead to assays capable of identifying individuals at increased risk of disease, and preventative (or therapeutic) measures to decrease those risks.
What are your hobbies?
My hobbies include making chain mail armor and artwork, and playing guitar.
What are the major challenges you face in your research with regards to sample collection, nucleic acid isolation and data analysis?
One of the biggest technical challenges in our research is the presence of various PCR inhibitors in biological samples, particularly fecal and soil samples. There are many different organic compounds that can inhibit the PCR reaction used to generate 16S rRNA amplicon libraries and if present at a high enough concentration, the template DNA will almost completely fail to amplify, resulting in a missed data point.
Which MO BIO or QIAGEN products do you use/have you used in the past and what did you like about the products?
We frequently use QIAGEN’s DNeasy PowerSoil and QIAamp PowerFecal DNA extraction kits for different sample types. The PowerFecal kits are particularly good at overcoming PCR inhibitors and are extremely user-friendly. We also rely heavily on a QIAGEN`s TissueLyser II for disaggregation of fecal samples prior to nucleic acid extraction.
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