The Oral and GI Microbiology Research Affinity Group (OGM RAG) at Nationwide Children’s Hospital which is housed in the Abigail Wexner Research Institute in the Center for Microbial Pathogenesis will bring together like minded clinicians and basic scientists that are actively involved in research in oral (e.g. tooth decay and periodontal disease) and gastrointestinal (e.g. inflammatory bowel disease, necrotizing enterocolitis) microbiology as it affects human disease. Importantly, these disciplines lead the field of human microbiome (the host microbial communities) research and how it contributes to general health. Both disciplines have made great progress in understanding how microbial community architecture can either benefit (eubiosis) or harm (dysbiosis) the host, strongly indicating that the microbes that populate our bodies contribute directly to our health. Further, the OGM RAG will also seek out contributions from other research disciplines where the microbiome plays an active role. The OGM RAG will thus create a university-wide network to leverage expertise and treat disease.
The OGM RAG is involved in multiple activities. In addition to quarterly meetings, the OGM RAG supports cross discipline multi-Principal Investigator projects particularly between basic researchers and clinicians to optimize translational outcomes. This creates an opportunity to train students across disciplines to prepare a new generation of investigators in these cutting-edge fields. Thus, the OGM RAG will bring this new, blended expertise from the bench to the bedside as we now understand that we, the host, are strongly affected by the microbes that live with us.
Topics of study: Studies in the Bailey lab seek to understand the impact that the intestinal microbiota have on the local immune system, and on immune reactivity at systemic sites, particularly during periods of psychological stress. Studies are primarily being conducted in pre-clinical animal models, such as models of inflammatory bowel disease, with the goal of translating these findings into meaningful clinical studies in human patients.
Example of OGM RAG-Related Project: We are interested in the dynamic interactions between host physiology and the gut microbiota. As a part of the Oral-GI Microbiology RAG, we are studying host-microbe interactions as they pertain to diverse diseases and conditions, including acute chest syndrome in children with sickle cell disease (collaboration with the Kopp lab), necrotizing enterocolitis (collaboration with the Goodman and Besner labs), responses to antibiotics and vaccines (collaboration with the Goodman and Bakaletz labs), and inflammatory bowel disease (collaboration with the Maltz lab). Our goal is to understand how to target the gut microbiome to develop microbiome-based therapies.
Topics of study: The Besner Laboratory focuses on the elimination of necrotizing enterocolitis (NEC), a devastating disease that primarily affects premature infants that is manifested by intestinal necrosis. Mortality exceeds 40% in low birth weight neonates, and there is a massive need for improvement in nearly every facet of NEC diagnosis and treatment. The Besner Lab performs cutting edge, novel research in both NEC diagnosis and treatment.
Example of OGM RAG-Related Project: As part of the Oral-GI RAG and in collaboration with the Goodman and Bailey Labs, we have developed a novel Lactobacillus reuteri (Lr)-based probiotic delivery system with proven efficacy in significantly reducing the incidence of NEC in a rat pup model of NEC. In addition, survivors of NEC often have developmental delays in later life related to cognition and memory gaps. Another line of inquiry is how the probiotic supplement may ameliorate these delays. Furthermore, this therapy protects the intestines from Clostridium difficile-associated colitis, and we are investigating its protective effects in other animal models of intestinal injury.
Steven D. Goodman, PhD
Topics of study: The Goodman Lab focuses on investigating bacterial biofilms, communities of bacteria that are encased in an extracellular matrix that protects them from the environment and are the primary physiologic state in the host. We study both making good biofilms using tunable probiotic bacteria to facilitate benefits to the host and getting rid of bad biofilms that are the cause of chronic and recurrent infections.
Example of OGM RAG-Related Project: In the oral cavity, we are focused on eliminating pathogens that cause dysbiosis (disturbances in the population of good bacteria allowing bad bacteria to dominate) the root cause of both tooth decay and periodontal disease. In the GI tract and in collaboration with OGM RAG members Gail Besner and Michael Bailey, we are working on formulations of probiotic bacteria that can be tuned to either eliminate dysbiosis and or specifically treat the host against a variety of indications including necrotizing enterocolitis and Clostridioides difficile.
John S. Gunn, PhD
Topics of study: The Gunn laboratory studies the pathogenic mechanisms of acute and chronic infections caused by the facultative intracellular pathogens Salmonella Typhi/Typhimurium and Francisella tularensis. They focus on virulence gene regulation, resistance to innate immune killing, chronic infection, biofilm formation and the development of new therapeutics/vaccines.
Example of OGM RAG-Related Project: Dr. Gunn’s research is particularly focused on bacterial biofilms and regulatory systems that control virulence and modifications of the bacterial cell surface in the context of acute and chronic infections. The Gunn lab developed a mouse model for chronic Salmonella infection of the gallbladder and uses this model to study both host and microbial factors that are responsible for establishing and maintaining asymptomatic, prolonged infection of this organ. Biofilm formation on gallstone surfaces was demonstrated to be the key mechanism of gallbladder carriage. Targeting Salmonella gallbladder carriage, we have identified new small compounds that inhibit biofilm formation and are testing additional therapeutic interventions to eliminate gallbladder/gallstone colonization. We are collaborating with the Goodman and Bakaletz labs to further understand clinical isolate variations in biofilm-forming ability and the contribution of DNABII binding proteins in biofilm development and dispersion.
Vanessa L. Hale, MAT, DVM, PhD
Topics of study: The Hale lab examines host-microbiome-disease interactions with the goal of understanding how host-associated microbial communities can shape disease susceptibility and pathogenesis. We study diseases that affect both humans and animals and use an ecological framework to evaluate microbe-microbe and microbe-host dynamics.
Example of OGM RAG-Related Project: One of our current projects focuses on characterizing the gut and urine microbiota associated with bladder cancer in dogs. Dogs, like humans, can get bladder cancer, or urothelial carcinoma, and studying cancer in dogs can help us improve both animal and human health. In humans, a major risk factor for the development of urothelial carcinoma is smoking. In dogs, a major risk factor is herbicide exposure. Polycyclic aromatic hydrocarbons (PAHs) are chemicals common to both cigarette smoke and herbicides. Our work examines if and how microbes in the gut and bladder may be metabolizing PAHs in relation to bladder cancer. Ultimately, we want to determine if the gut or urine microbiota can help us predict, prevent, or treat diseases like bladder cancer.
Topics of study: The King laboratory focuses on defining interactions between streptococcal species and their hosts in the context of both health and disease. Specifically, our work is focused on defining the mechanisms by which these species bind relevant host surfaces with the long-term goals of improving health and reducing the burden of disease.
Example of OGM RAG-Related Project: We recently identified highly unusual monolateral fibrils on the surface of the oral bacterium Streptococcus oralis subsp. dentisani. This bacterium is associated with oral health but can enter the bloodstream and cause infective endocarditis. We have determined that the fibrils are serine rich repeat proteins that bind both bacterial and host surfaces. Our current studies aim to define not only the mechanisms by which these fibrils mediate binding, but also those which result in the monolateral distribution. These studies will define the first binding mechanisms for this subspecies and increase our understanding of bacterial protein secretion and distribution.
Topics of study: The Kopp laboratory focuses on host-pathogen interactions that impact chronic respiratory diseases such as cystic fibrosis (CF) and lung disease related to sickle cell. Our studies with human cell models are used to develop novel therapeutics and find new targets to allow for improved killing of bacteria and regulation of hyper-inflammatory signaling in chronic respiratory diseases.
Example of OGM RAG-Related Project: We are interested in how the microbiome is influenced by and also influences innate immune signaling. As a part of the Oral-GI RAG and in collaboration with the Bailey lab we have been investigating transcriptomic and microbiome changes that occur during Acute Chest Syndrome in children with sickle cell. Our goal is to understand shifts in bacterial populations and the corresponding gene regulatory changes that occur during Acute Chest Syndrome to help clarify and improve the current paradigm of antibiotic treatment for all Acute Chest Syndrome cases.
Topics of study: The Lauber lab focuses on how microbial community function affects health and the development of new methods to interrogate the microbiome. Our lab uses meta’omic approaches with in vitro and in vivo models to understand how microbiome function varies across individuals and diseases states.
Example of OGM RAG-Related Project: We are interested in describing the microbiome in terms of functional capability in addition to the traditional ‘who is there’ approach to better understand how microbial diversity drives host responses. Our goal is to use these data to define what constitutes a healthy microbiome and translate these observations into treatments for acute and chronic diseases.
Topics of study: The Maltz laboratory focuses on the effect stressor exposure has on intestinal inflammation via alterations in the gastrointestinal microbiome and metabolome. Our studies utilize murine models of IBD and prospective clinical studies in pediatric Inflammatory Bowel Disease patients.
Example of OGM RAG-Related Project: As a part of the Oral-GI RAG and in collaboration with Dr. Bailey and Dr. Lauber we are investigating whether biofeedback therapy which is a stress reduction therapy can impact disease activity in pediatric Crohn’s disease patients and attenuate the stress related effects in the microbiome and metabolome. Our goal is to identify a complimentary therapy that can attenuate stress related effects on inflammation in order to further improve Crohn’s disease activity. In addition, identify a biomarker/signature that can predict which patient population would most likely benefit from this stress reduction therapy.
Topics of study: Janice Townsend, DDS, MS has a variety of research interests including pain management following dental procedures, dental materials, and dental education.
Example of OGM RAG-Related Project: Dr. Townsend is currently collaborating with the Griffen-Leys Lab at The Ohio State College of Dentistry to better understand the relationship between oral health interventions and oral microbiome changes in patients undergoing hematopoetic stem cell transplant with the goal of reducing morbidity and mortality.
Jenessa A. Winston, DVM, PhD, DACVIM
Topics of study: Dr. Jenessa Winston is an Assistant Professor at The Ohio State University College of Veterinary Medicine. As a veterinarian clinician scientist, Dr. Winston’s strives to enhance animal and human health through translation scientific discoveries. Her primary research interests include microbe-host interactions during health and disease and rational manipulation of microbial ecosystems including interventions such as fecal microbiota transplantation.
Example of OGM RAG-Related Project: Obesity is a growing epidemic in humans and companion animals. Evidence is mounting that the intestinal microbiota contributes to an “obesogenic” phenotype, and rational manipulation of this ecosystem may confer a health benefit. We aim to provide a comprehensive scientific and clinical assessment of the efficacy of fecal microbiota transplantation (FMT) as an adjunctive therapy for canine obesity management. We hypothesize that FMT will amplify weight loss compared to the use of standard dietary obesity management. To test this, we will conduct a 24-week randomized, double-blinded, placebo controlled, cross-over clinical trial in client-owned obese dogs. Using an integrated multi-omics approach the intestinal microbiota will be comprehensively evaluated every 6 weeks via16S rRNA gene sequencing and global untargeted metabolomics. Project execution will provide evidence for FMT efficacy in obesity management and facilitate rational manipulation of the intestinal ecosystem into a personalized medicine approach for dogs suffering from obesity.