Doctor of Philosophy, The Ohio State University, 2024, Oral Biology

Maternal health is emerging as a critical long-term determinant of a child's health. For example, stressful life events or anxiety during pregnancy are associated with increased risk of emotional, behavioral, and cognitive issues in the child. Children born to mothers experiencing famine during late gestation have an increased risk of developing metabolic disorders, while maternal type II diabetes mellitus causes impaired glucose tolerance and obesity in the offspring. While most human microbiome studies are correlational, mouse studies suggest that the maternal gut microbiome influences the offspring's metabolic system. Therefore, promoting the health of women, especially pregnant women, promotes the well-being of children. As pregnancy is associated with a pathogen enriched oral microbiome and the infant oral microbiome may be influenced by the mother, we are interested in first investigating the effect pregnancy has on the maternal oral microbiome and second, in investigating patterns and processes in the vertical transmission of the maternal oral microbiome, and the impact of perturbations on the biome of the offspring. Longitudinal studies using metagenomic sequencing methodology were combined with a comprehensive systems biology approach to characterize the taxonomic composition, functional characteristics, and vertical inheritance patterns. These investigations revealed that the infant microbiome is seeded by the maternal microbiome and affected by various maternal exposures like smoking, antibiotic usage, and gestational diabetes. Furthermore, we found evidence that maternal oral bacteria translocate to the placenta via the serum and may play a role in training the infant immune system to accept certain bacteria after birth.

Committee: Binnaz Leblebicioglu (Advisor); Shareef Dabdoub (Committee Member); Haikady Nagaraja (Committee Member); Sarah Peters (Committee Member) Subjects: Biology; Dentistry; Health Sciences; Medicine

Master of Science, The Ohio State University, 2024, Microbiology

The human gut microbiome is the collection of the microbiota that reside in the human intestinal tract. Imbalances in the gut microbiome are associated with multiple diseases, so studying this is important for preventing and treating these conditions. These imbalances can have multiple causes, such as changes in core temperature. Previous work has indicated that the gut microbiome could play a role in mitigating negative effects of temperature on epithelial tissues, which could have profound effects on human health. Research into the human gut is normally performed by way of animal models, or by using a synthetic model involving the use of human cells on transwells. The goal of this study was to collect preliminary data to determine if gene expression in gut epithelial cells is influenced by the presence of a fecal sample at hypoxic, hyperthermic conditions. An experiment was performed on 36 gut-on-a-chips over the course of 48 hours at three different temperature levels: 30°C, 37°C, and 42°C. Next-Generation Sequencing (NGS) was performed to determine gene expression in the human epithelial cells when comparing the introduction of a fecal sample to the chip in low-oxygen conditions at 42°C. Most genes in the host cells were upregulated when exposed to the fecal sample, with the majority being involved in immune system responses, as well as cell growth and differentiation, host metabolism, and enzymatic activity, which is consistent with what would be expected when the gut bacteria are present. The gut-on-a-chip can be used to study temperature effects on the human epithelial cells, as well as test ways to counteract any negative effects that come with this shift. Future studies can elucidate the role that the gut microbiome may play in the response of the human body to changes in core temperature.

Committee: Karen Dannemiller (Committee Chair); Joshua Hagen (Committee Member); Justin North (Committee Member) Subjects: Biology

Master of Science (MS), Bowling Green State University, 2023, Biological Sciences

Fraxinus ash trees in North America a threatended by the invasive Agrilus planipennis, emerald ash borer (EAB). EAB infestation has wide ranging economic, cultural and ecological impacts upon the North American environment. This study aims to look at the biological impact that infestation of ash trees can have on the soil microbiome around the tree's roots. A previous study has already examined the possible geochemical effects of the trees sampled, and by looking at the effects on the microbiome through 16S ribosomal sequencing, we hoped to gain some estimation of the effect imposed on microbiota surrounding the tree. With a combination of alpha, beta, and network analysis, we can see some possible changes within the rhizosphere associated to the health of trees. Alpha diversity was inconclusive as there was inconsistent data amongst our sampled set of trees. There is confounding points in the data pertaining to geographic differences in sample locations. However, when stratifying to sample locations, beta and network analyses show shifts in the microbiome are significant, with site 2 and 4 beta diversity showing a progression of microbiome makeup to change as health state changed. Differential networks between health states indicate a change in taxa between healthy and unhealthy tree rhizopheres exist. The network topography as well as the strength of edges between networks showed a difference in taxonomic makeup comparing health states with some phyla of note being Verrucomicrobia, Nitrospirae, and Acidobacteria. Because our sample size within each location was small, we recommend further studies be done to explore those differences.

Committee: Zhaohui Xu Ph.D. (Committee Chair); Jungfeng Shang Ph.D. (Committee Member); Angelica Vazquez Ortega Ph.D. (Committee Member) Subjects: Bioinformatics; Biology; Microbiology

Doctor of Philosophy, Case Western Reserve University, 2021, Pathology

Multifactorial diseases such as diabetes, allergy and asthma, inflammatory bowel disease and neurodegenerative disorders have increased in recent years. Genetic predisposition is unable to fully account for this sudden increase, yet our environment is a factor that has seem similar dramatic changes even in the last 100 years. It has since become apparent that the gene pool of endogenous microbes that populate our bodies might be more susceptible to these changes due to their shorter life span and generation turnover. Thus, examination of the microbiome has become a major focus in the hopes of identifying underlying changes in the microbiome which may give rise to or be compounded due to disease. Study of these interactions have revealed the involvement of the microbiome in many functions ranging from processing of nutrients, neuronal and immune system development. The host immune interactions with gut commensal microbes have demonstrated their importance in establishing tolerance and maintenance of homeostasis. Here, we utilized the capsular polysaccharide PSA produced by the gut commensal Bacteroides fragilis to better understand the impact on the host immune system locally and systemically. Prior work established that PSA is endocytosed, processed and presented by APCs to CD4+ T cells via MHCII molecules. This exposure lead to the expansion of a population of C45Rblow effector memory (Tem) cells capable of protecting from induction of inflammation. This protection was shown to be IL-10 dependent, the source of which was endogenous Tregs and not the PSA expanded cells. Through in vitro co-culture experiments with regulatory T cells, we demonstrated a novel T cell communication axis by which Tem cells secrete IL-2 and IL-4 to synergistically stimulate IL-10 production by Tregs. Furthermore, we demonstrated that PSA exposure results in potent interferon response, which results in the upregulation of immune-regulatory markers. These markers were primarily found (open full item for complete abstract)

Committee: Brian Cobb PhD (Advisor); Booki Min DVM, PhD (Committee Chair); Kristie Ross MD (Committee Member); Pushpa Pandiyan PhD (Committee Member); Clive Hamlin PhD (Committee Member) Subjects: Immunology

Master of Science, The Ohio State University, 2020, Plant Pathology

It has been documented that beneficial plant-associated bacteria have contributed to disease suppression, growth promotion, and tolerance to abiotic stresses. Advances in high-throughput sequencing have allowed an increase in research regarding bacterial endophytes, which are microbes that colonize the interior of plants without causing disease. Practices associated with minimizing the use of off-farm resources, such as reduced tillage regimes and crop rotations, can cause shifts in plant-associated bacteria and its surrounding agroecosystem. Integrated crop–livestock systems are an option that can provide environmental benefits by implementing diverse cropping systems, incorporating perennial and legume forages and adding animal manure through grazing livestock. It has been found that crop-livestock systems can increase soil quality and fertility, reduce cost of herbicide use and improve sustainability, especially for farmers in poorer areas of the world. This work explores how crop-livestock systems that integrate chicken rotations can impact tomato plant growth, as well as soil and endophytic bacterial communities. Tomato plants were subjected to greenhouse and field studies where biomass was assessed, and bacterial communities were characterized through culture-dependent and -independent approaches. In greenhouse experiments, the greater percent of chicken grazed soil incorporated in the planting substrate, the greater the stunting of tomato seedlings. In the field study, bacterial communities differed significantly by sample origin and plant development stage, regardless of chicken grazing history. Our findings suggest stronger contribution of agricultural management practices during early plant stages on endophytic microbiome, as opposed to later on in the host lifecycle. Taxonomic composition of dominant groups of recovered endophytic bacterial isolates were consistent with those found by amplicon sequencing. Plots with history of chicken grazing had a sig (open full item for complete abstract)

Committee: Maria Soledad Benitez-Ponce Ph.D. (Advisor); Christine Sprunger Ph.D. (Committee Member); Jonathan Jacobs Ph.D. (Committee Member) Subjects: Agriculture; Biology; Ecology; Microbiology; Plant Pathology; Soil Sciences

Master of Science, The Ohio State University, 2020, Food Science and Technology

Tomato consumption has been associated with a number of health benefits, many of which are reduced risks for chronic diseases prominent in the US. Considerable attention has been paid to the health benefits to lycopene, the red-colored carotenoid in tomatoes. However, whole tomato has been shown to provide more benefit than lycopene alone. The tomato fruit is a complex system containing thousands of small molecules, many of which have not been studied for their action in the human body. This research aims to investigate two ways in which tomato phytochemicals may influence human health. The first of these is elucidation of tomato steroidal glycoalkaloid absorption and metabolism after tomato consumption. Steroidal glycoalkaloids are an understudied class of secondary plant compounds that have recently been shown to be absorbed from the diet and deposited in tissue, and have bioactive properties in vitro and in vivo. There is little information regarding what happens to these compounds once they are consumed from tomatoes. In order to understand potential bioactivity of tomato steroidal glycoalkaloids, it is important to know how these compounds are metabolized and distributed. To investigate tomato steroidal glycoalkaloids in vivo, we conducted a parallel study in weaned piglets (aged three weeks), a physiologically relevant model for humans, fed a control diet (n=10) or a diet containing 10% tomato powder (n=10) for two weeks. Blood plasma samples were analyzed for tomato steroidal glycoalkaloids via UHPLC-QTOF-MS. Nine masses were putatively identified as steroidal alkaloids or their metabolites. It was found that most sugar moieties are cleaved, and the remaining aglycones undergo phase I and II metabolism, namely hydroxylation and sulfonation. This information provides a basis for further research on understanding the bioactivity of tomato steroidal glycoalkaloids in humans and their potential for health benefit. The second study was an exploration of effects of (open full item for complete abstract)

Committee: Jessica Cooperstone Ph.D. (Advisor); Rachel Kopec Ph.D. (Committee Member); Devin Peterson Ph.D. (Committee Member) Subjects: Food Science

PhD, University of Cincinnati, 2020, Medicine: Industrial Hygiene (Environmental Health)

Exposures to both biological aerosols and traffic-related air pollution have well-documented adverse health effects. These exposures are relevant to public, environmental, and occupational health. The goal of this study was to further our understanding of biological aerosol and traffic pollution exposure by providing new insight into the impacts of traffic pollution on the body, and by examining ways in which to measure biological aerosol exposure. This dissertation consists of three related aims. The objectives of the first two aims were to examine the effect of traffic pollution exposure on the respiratory microbiome and to characterize and compare the microbial communities of the respiratory tract and home dust, which is representative of the bioaerosol exposure in the home. The objective of the third aim was to compare two bioaerosol measurement methods and examine the effect of traffic pollution on those methods. In Aim 1, we collected induced sputum samples from a longitudinal cohort of adolescents with a well-characterized traffic pollution exposure history. Metagenomics sequencing, specifically 16s rDNA for bacteria and ITS rDNA for fungi, was used to compare the microbial communities in the sputum of the adolescents in the high and low traffic pollution exposure groups. A linear regression model was used to examine the association of traffic pollution exposure and microbial diversity in the lower respiratory tract. In Aim 2, the sputum and saliva samples collected for Aim 1 were characterized along with home dust samples taken from the same participants. The bacterial and fungal diversity and community compositions of each sample type were compared. Quantitative polymerase chain reaction was used to quantify the total bacterial and fungal load in each sample type. We also examined the differences in the microbial communities of home dust between traffic pollution exposure groups, genders, and asthma status. In Aim 3, two culture-independent bio (open full item for complete abstract)

Committee: Tiina Reponen Ph.D. (Committee Chair); Jaroslaw Meller Ph.D. (Committee Member); Nicholas Ollberding (Committee Member); Patrick Ryan Ph.D. (Committee Member); Jurate Virkutyte Ph.D. (Committee Member) Subjects: Environmental Health

Master of Science (M.S.), University of Dayton, 2020, Biology

There are many ways in which microbiomes can influence the health and fitness of their insect hosts. While much research has been done on the microbiomes of economically important species like honeybees, and charismatic groups like butterflies, little work has been done to understand the microbiome of grasshoppers and katydids. Grasshoppers are an important herbivore in grassland ecosystems and provide important ecosystem services like nutrient cycling. Alternatively, grasshoppers can be a pest organism requiring management and control. In relationship to the total ecosystem, the limitation of abiotic factors like essential nutrients can influence the abundance and fitness of insect herbivores such as grasshoppers. However, the effect of these abiotic factors on grasshopper microbiomes is largely unknown. Using culture-independent, high-throughput 16s and ITS sequencing and statistical analysis, we examined the gut microbiome of six species of grasshoppers (n=60) from the site of a fully-factorial fertilization experiment in a coastal tallgrass prairie ecosystem in order to gain a better understanding of the microbial communities present across the orthopteran order in this ecosystem. We also examined the relationship between environmental nutrients and gut microbes of one orthopteran species, Orchelimum vulgare. Our observations support the hypothesis that there is a “core” group of bacterial families in these grasshopper species and factors such as trophic behaviors and the evolution of the host may contribute to the shifts in prevalence among these core microbial groups. We also found significantly higher Shannon diversity in the gut bacterial communities of those grasshoppers from plots fertilized with added sodium in contrast to plots without sodium. There is significantly lower diversity in gut fungal communities from plots amended with nitrogen and phosphorus, as well as sodium, suggesting that both nitrogen and phosphorus and sodium are limiting nutrients fo (open full item for complete abstract)

Committee: Yvonne Sun Dr. (Advisor); Chelse Prather Dr. (Committee Member); Ryan McEwan Dr. (Committee Member) Subjects: Biology; Ecology

Master of Sciences, Case Western Reserve University, 2020, Biology

The “mycobiome" refers to the composition of both bacterial and fungal communities in the human gut microbiome and has been the focus of disease-state correlations investigated by researchers and pursued with commercial interests by biotech startups. A microbiome startup currently sells direct-to-consumer at-home microbiome sequencing kits and probiotics that aim to balance the gut biofilm that contributes to the dysbiosis-associated conditions. This company has expressed an interest in developing new business strategies to leverage their intellectual and technical strengths. This thesis is composed of two parts: The first section is a scientific and technical investigation of the micro- and myco-biome, sequencing techniques and strategies (16S, ITS, WGS, and Shotgun Metagenomic Sequencing) that play a role in the characterization and identification of fungal and bacterial colonies in the gut. These strategies aim to overcome challenges in characterizing and quantifying microbiota composition. Next, this sequencing data can form a robust database of patient data that plays a role in disease identification, and this thesis identifies some of the bioinformatic analyses to achieve this goal. The section concludes with how insights derived from patient data can be used in the optimization of cohort design in clinical trials for various diseases. The second section investigates three different business models that a microbiome startup has expressed interest in exploring for future development: (1) medical foods; (2) a therapeutic pipeline; and (3) a data-licensing and discovery platform for drug development. A detailed analysis of the market dynamics, competitive landscape, regulatory issues, and other nascent concerns was performed for each potential vertical as a foundation to develop future business strategy of a microbiome-related startup. The thesis is concluded on a holistic analysis of the scientific and technical assets and business opportunities and str (open full item for complete abstract)

Committee: Christopher Cullis (Committee Member); Emmitt Jolly (Committee Member); Neema Mayhugh (Committee Member) Subjects: Biology; Entrepreneurship

PhD, University of Cincinnati, 2024, Pharmacy: Pharmaceutical Sciences

There is increasing recognition of the pivotal role of the microbiome in addressing numerous questions about human health and disease. Exploring the role of the microbiome in the gastrointestinal tract and skin – the two largest reservoirs of the human microbiota – can provide valuable insights into the pathology and treatment of various diseases. Our first specific aim was to investigate the translocation of gut bacteria to the heart in a murine model of myocardial infarction (MI). In a novel discovery, we demonstrated that gut bacteria, which permeate into the systemic circulation after myocardial infarction, can colonize and proliferate within the heart, thus uncovering the existence of the heart microbiome. This observation was further validated through various techniques by using E. coli Nissle 1917 (EcN) as a tracer bacterium. Our second aim was directed towards developing a gut microbiome-based therapeutic construct to treat post-MI intestinal hyperpermeability. We engineered EcN to express F. prausnitzii-derived microbial anti-inflammatory molecule (MAM) and investigated its safety, efficacy, and mechanism of action in the MI model. Treatment with our recombinant construct, EcN-MAM, resulted in increased survival, enhanced cardiac function, and decreased cardiac fibrosis compared to the placebo group. As an exploratory aim, we also investigated the potential use of microbiome-based constructs for dermatological applications. We engineered EcN to express shinorine, a natural sunscreen, and evaluated its efficacy in an ex vivo human and porcine skin models of ultraviolet radiation (UVR)-induced DNA damage and a reconstructed human epidermis model of UVR-induced reactive oxygen species (ROS) damage. We found that our developed construct, EcN-SH, was effective in protecting against both UVR-induced DNA damage and ROS damage.

Committee: Nalinikanth Kotagiri Ph.D. (Committee Chair); Pankaj Desai Ph.D. (Committee Member); Zalfa Abdel-Malek Ph.D. (Committee Member); Kevin Li Ph.D. (Committee Member); Kavssery Ananthapadmanabhan ENG.SC.D. (Committee Member) Subjects: Pharmaceuticals

Doctor of Philosophy, Miami University, 2024, Biology

CHAPTER 1: Nutrient excretion by fish supports a variable but significant proportion of lake primary productivity over 15 years. This chapter analyzes the long-term importance of excretion from gizzard shad for primary production in a midwestern reservoir using a supply:demand (S:D) approach and considers environmental and population variables that best predict the S:D ratio. Gizzard shad excretion supported a variable proportion of phytoplankton phosphorus demand, and it supported more demand during the summer than spring. Stream discharge, temperature, and gizzard shad population biomass best predicted S:D during the spring, while the biomass of the young-of-year best predicted S:D in the summer. CHAPTER 2: Combined influence of parasites and temperature on nutrient excretion rates and body stoichiometry of a freshwater fish. The rates of excretion from fish and the ratios of the nutrients excreted are expected to change as aquatic ecosystems warm. An experiment examined the excretion rates from bluegill under three climate scenarios and a range of natural parasite intensity. Carbon and phosphorus excretion increased with temperature but declined with parasite load, and the C and N concentrations in fish bodies declined with parasite load. CHAPTER 3: Ontogenetic changes in the gut microbiomes of Gizzard Shad and Bluegill and their relationship to nutrient excretion. The microbial communities within the guts of animals contribute to their health, but little is known about how these communities change with development and contribute to ecosystem processes. We conducted an exploratory study to learn about the gut microbiome of larval, young-of-year, and adult gizzard shad and bluegill as well as the relationship between microbiomes and excretion. We found that the two fish species had similar microbial communities as larvae, but the communities were different in the adults. The guts of adult gizzard shad contained taxa that are believed to fix nitrogen as well as s (open full item for complete abstract)

Committee: Michael Vanni (Advisor); Melany Fisk (Committee Member); Matthew Saxton (Committee Member); Roxane Maranger (Committee Member); Christopher Myers (Committee Member); María González (Committee Member) Subjects: Biogeochemistry; Biology; Environmental Science; Limnology; Science Education

Master of Science, The Ohio State University, 2024, Veterinary Preventive Medicine

The urinary tract contains a distinct and diverse set of microbiota (urobiome). Important work has established links between the composition of the urobiome and various diseases of the urinary tract, including bladder cancer, urolithiasis, incontinence, and recurrent urinary tract infection. However, efforts to characterize the urobiome and assess its functional potential have been limited due to technical challenges including low microbial biomass and high host cell shedding in urine. To begin addressing these challenges, we evaluate urine sample volume (100 l – 5 mL), and host DNA depletion methods and their effects on urobiome profiles in healthy dogs, which are a robust large animal model for the human urobiome. We collected urine from seven dogs and fractionated samples into multiple aliquots. One set of samples was additionally spiked with host (canine) cells to model a biologically relevant host cell burden in urine. Samples then underwent DNA extraction followed by 16S and shotgun metagenomic sequencing. We tested six methods of DNA extraction: QIAamp BiOstic Bacteremia (no host depletion), QIAamp DNA Microbiome, Molzym MolYsis, NEBNext Microbiome DNA Enrichment, Zymo HostZERO, and Propidium Monoazide. Sequences were processed and analyzed using QIIME2 and MetaPhlAn4. Metagenome assembled genomes (MAGs) were generated using MEGAHIT and MetaWRAP pipelines. Statistical analysis were performed in R. In relation to urine sample volume,  3.0 mL resulted in the most consistent urobiome profiling. In relation to host depletion, individual (dog) but not extraction method drove overall differences in microbial composition. DNA Microbiome yielded the greatest microbial diversity in 16S (p=0.0025) and shotgun metagenomic data (p=0.01), and maximized MAG recovery while effectively depleting host DNA (p=0.0039) in host-spiked urine samples. As proof-of-principle, we then mined MAGs for core metabolic functions and environmental chemical metabolism. We identified long c (open full item for complete abstract)

Committee: Virginia Rich (Committee Member); Vanessa Hale (Advisor); Brian Husbands (Committee Member) Subjects: Biomedical Research; Microbiology; Molecular Biology

Master of Science, The Ohio State University, 2024, Food Science and Technology

In the human gut, there are trillions of microorganisms shaping complex networks, so-called ‘human gut microbiota'. The members of human gut microbiota are linked to each other by metabolic interactions and the functions encoded in their genome, which is called ‘human gut microbiome'. The gut microbiome interacts with humans, the host, in various paths. For example, their metabolites modulate cellular physiology by being attached to surface receptors or involving in epigenetic modifications. In addition, cellular components of gut microorganisms work as a ligand of pattern recognition receptors, which is important in host immunological modulation. Moreover, those kinds of exposures in a proper time window of the human growth stage are crucial in early life development. Hence, gut microbiome affects human health from one's birth to death. There are multiple factors affecting the human gut microbiome, which can be classified into two, internal (e.g., genetic) and external (e.g., environmental, social, behavioral, cultural) factors. Based on the internal attributes of the host, gut microbiota colonizes and changes via interacting with external factors. Among external factors, delivery mode, breastfeeding, antibiotics treatment, lifestyle, and diet have been studied extensively. Yet, the most important factors affecting gut microbiome has been agreeable to be diet in many studies. As an energy source of gut microbiota, foods, administered into large intestine shapes gut microbial composition. Properties of macronutrients and micronutrients in food, such as digestibility and physicochemical characteristics are important in shaping gut microbiome. However, since many people still do not have such profound knowledge of nutrition, their dietary behavior is determined by social factors, including socioeconomic status, demographical, belief and philosophy, culture, or religion. Therefore, the objective of this thesis was examining how such social and environmental (open full item for complete abstract)

Committee: Jiyoung Lee (Advisor); Vanessa Hale (Committee Member); Ahmed Yousef (Committee Member) Subjects: Food Science

Master of Science, The Ohio State University, 2024, Dentistry

Introduction: Although having been introduced ten years ago, little is known of the impact of electronic nicotine delivery systems (ENDS) on human health. ENDS usage is rapidly rising among adolescents and young adults and this is partially due to a perception that ENDS are safer than cigarettes and nicotine replacement therapies. However, these products vary widely in nicotine content, propylene glycol, glycerol, additives and flavorings; all of which are poorly studied, and it is possible that may deliver toxins that interfere with a variety of bodily processes. Therefore, there is an urgent need for biological investigations that will improve our understanding of how ENDS impact human health. The initial point of contact of ENDS, and the first-affected system in humans is the oral cavity. It is known that nicotine adversely impacts oral health, acting as a cytotoxic agent and pro-inflammatory mediator, as well as negatively impacting the oral microbiome. Oral health is dependent upon an intricate balance between the microbial ecosystem and host immunity. Objective: Based on our preliminary studies that ENDS alter the compositional structure and the functional potential of the oral ecosystem, we hypothesized that ENDS impacts this microbial-mucosal homeostasis. We tested this hypothesis by comparing host-microbial dynamics during de-novo colonization of the subgingival microbiome among systemically and periodontally healthy e-cigarette users and non-smoker healthy controls. Methods: A 12-week prospective, case-control study was performed on 30 periodontally and systemically healthy subjects, with 10 e-cigarette users and 20 non-user controls. Plaque, gingival crevicular fluid, and saliva samples were obtained from both the groups at screening visit, after which oral prophylaxis was performed. Samples were collected 1, 2, 4, 7, 14, 21, 30, 60, 90 days after prophylaxis. The samples were subjected to whole genome shot gun sequencing and semi-quantitative targete (open full item for complete abstract)

Committee: Binnaz Leblebicioglu (Advisor); Yi-Chu Wu (Committee Member); Purnima Kumar (Committee Member) Subjects: Dentistry

Doctor of Philosophy, The Ohio State University, 2024, Microbiology

Signal transduction is an essential part of how bacteria sense and respond to their internal and external environments. Signal transduction is mediated by three different types of systems: one-component systems, two-component systems, and chemosensory systems. Each system receives an input through a sensory domain resulting in the creation of a signal that leads to a cellular response. Extracytoplasmic sensory domains are important for how bacteria sense their external environment. Two major families of extracytoplasmic domains are the Cache Superfamily and the Four Helical Bundle Superfamily. We are interested in studying signal transduction is the human gut microbiome. The human gut is extremely diverse and varies between individuals making it difficult to study. Human gut commensals are widely unexplored because many of the organisms in the microbiota cannot be cultured. Here, we begin to explore signal transduction pathways that are found in common bacterial commensals found in the human gut microbiota. We identify thousands of extracellular sensory domains, and we characterize binding motifs for several dCache_1, sCache_2, and Cache _ 3-Cache _ 2 domains. By better understanding extracellular sensory domains in these organisms, we can learn more about what molecules in the gut contribute to commensal proliferation. Interestingly, in the gut commensal Akkermansia muciniphila, the only Verrucomicrobiota member commonly found in the gut, we have found only one histidine kinase that potentially contains a putative extracytoplasmic sensory domain. Structural modeling suggests that this hypothetical domain resembles a dCache domain. This domain should be further investigated to determine its functionality.

Committee: Igor Jouline (Advisor); Jesse Kwiek (Committee Member); Patrick Bradley (Committee Member); Irina Artsimovitch (Committee Member) Subjects: Microbiology

Doctor of Philosophy, The Ohio State University, 2024, Food Science and Technology

Food safety inadequacies constitute a substantial global hazard, not only influencing human health but also bearing serious implications for animal health and environmental sustainability. The sources of food contaminants are diverse, ranging from polluted food production environments during food production to deficient practices in transportation, and inadequate storage conditions. The pollutants that contaminate our food supply can be broadly classified into physical, chemical, and biological. Among biological contaminants, pathogens and microbe-derived metabolites are largely responsible for precipitating foodborne diseases. The built environment—comprising agricultural lands, livestock, aquaculture farms, food industry and consumers settings,—is deeply impacted by microbial threats. It is crucial to provide an effective and environmentally friendly method to modulate biological threats. In the meantime, from a personal environment, it is not only essential to minimize the contact with hazards, but also important to seek an effective and convenient way to mitigate the harmful impacts of the exposure in our daily life. This method should encompass reinforcing human health defenses. This dissertation presents an innovative exploration of two effective approaches aimed at protecting health under a high-risk (cancerous) condition in a personal environment with diet intervention and controlling biological contamination at a built environment level with an environmentally friendly technique. Chapter 2 and 3 investigate the effectiveness of polyphenol-rich diet, black raspberry (BRB), on gut microbiota and their function, with a particular focus on its application for negating harmful effects from carcinogen exposure in high-risk populations. For this, we applied a carcinogenesis mouse model and simulated black raspberry ingestion to determine whether this diet can be an effective way for health risk intervention at a host level. 16s rRNA sequencing and metagenomic (open full item for complete abstract)

Committee: Jiyoung Lee (Advisor); Ahmed Yousef (Committee Member); Rafael Jimenez-Flores (Committee Member); Jessica Cooperstone (Committee Member) Subjects: Food Science

Doctor of Philosophy, The Ohio State University, 2024, Dentistry

Despite having been introduced over 10 years ago, there is little research into the effects of electronic cigarettes (e-cigs, electronic nicotine delivery systems, or ENDS) on health outcomes. These devices create an aerosol mixture by heating propylene glycol, glycerol, nicotine, additives and flavorings. Although concerns have been voiced about these devices, usage continues to increase, partially because they are marketed as a safer alternative to traditional cigarettes and as a smoking cessation aid. However, the chemicals in ENDS may deliver toxins to a variety of body systems, necessitating an urgent need for investigation into their biological effects. The oral cavity is the initial point of contact and the primary repository of nicotine deposition, which places the oral microbial environment at a high potential to be impacted by ENDS. Oral microbial homeostasis relies on an intricate balance between the host and their microbiome, but disruptions to this equilibrium can have wide-reaching effects. The purpose of this investigation was to examine the multi- faceted impacts of ENDS on the different systems within the oral cavity, ranging from the microbiome to the human host, and the signaling molecules that connect these two. A tandem approach of in vitro and in vivo techniques was utilized to recapitulate the oral microenvironment and identify the mechanistic changes while also allowing for clinical correlations to be made. Systems were analyzed with a multi omics approach consisting of host transcriptomics, metatranscriptomics and metabolomics in combination with mass spectrometry and immunohistochemistry to identify potential biomarkers and risk for disease.

Committee: Binnaz Leblebicioglu (Advisor); Purnima Kumar (Advisor); Shareef Dabdoub (Committee Member); Haikady Nagaraja (Committee Member); Emmanouil Chatzakis (Committee Member) Subjects: Dentistry

Doctor of Philosophy, The Ohio State University, 2024, Biomedical Sciences

Cancer patients experience debilitating physiological (e.g., gastrointestinal) and behavioral (e.g., cognitive decline) symptoms due to the cancer itself and subsequent cancer treatments. These symptoms are related to reduced quality of life and treatment delays and dose reductions, thereby increasing patient mortality. Inflammation and gut microbiome disruptions are both commonly hypothesized to play a role in these symptoms. Here, I investigate the extent to which breast cancer and chemotherapy independently and synergistically cause immune dysfunction, gut microbiome disruption, and physiological and behavioral symptoms. Chapter 2 characterizes a comprehensive breast cancer mouse model in terms of immune, neuroimaging, and behavioral effects. In this model, chemotherapy induced inflammation, neuroimaging alterations, and reduced locomotor activity. In chapter 3, I demonstrate that mammary tumors blunt microglial and behavioral responses to immune challenges in mice. This impairment of immune and behavioral responses is specific to a peripheral route of immune challenge administration, suggesting a non-brain-specific mechanism. Chapter 4 demonstrates that chemotherapy induces gut microbiome disruption, elevates circulating TNF-α, and induces cognitive decline in breast cancer patients. Furthermore, cognitive decline is related to decreases in microbial diversity but not elevated circulating cytokines. Finally, in chapter 5, I show that decreased gut microbial diversity prior to chemotherapy treatment predisposes breast cancer patients to chemotherapy-induced gut microbiome disruption and gastrointestinal symptoms. The findings of this work demonstrate that tumors lead to immune dysfunction and behavioral consequences in a preclinical model of breast cancer. Furthermore, this work delineates the roles of chemotherapy-induced gut microbiome disruption and inflammation in the development of cognitive decline and gastrointestinal symptoms in a population of breast can (open full item for complete abstract)

Committee: Leah Pyter (Advisor); Baldwin Way (Committee Member); Jonathan Godbout (Committee Member); Tamar Gur (Committee Member) Subjects: Biomedical Research

PhD, University of Cincinnati, 2024, Medicine: Immunology

Newborns and young children are particularly susceptible to infection compared to other age groups. Lower respiratory tract infections, such as pneumonia, comprise the majority of cases and are the leading cause of mortality for children under 5 years old. This vulnerability was largely attributed to immature immune responses in newborns. Recent studies support a newer paradigm in which neonatal immunity is uniquely situated for balancing responses to pathogens with tolerance to developmental processes and environmental exposures.

After birth, there is an immediate and immense environmental exposure to the world of microbes, some of which go on to colonize the intestinal tract and live commensally with the newborn. Prior work in the lab showed that exposure to antibiotics early in life, and the resulting disruption of the microbiota, causes impaired pulmonary immune responses. It is unknown though whether this connection between development of the commensal microbiota and pulmonary immunity is translationally relevant to human newborns and their susceptibility to lower respiratory tract infections. It is also unclear whether the commensal microbiota is important more broadly for control of both innate and adaptive pulmonary immune responses early in life, and if so, how.

Chapter 2 of this dissertation uses a Rhesus macaque model to show that exposure to a clinically relevant cocktail of antibiotics disrupts the developing microbiota early in life, which then compromises pulmonary neutrophil responses to bacterial pneumonia. Newborn macaques exposed to antibiotics have worsened outcomes to pneumonia, which associated with the emergence of an aged, hyperinflammatory subset of neutrophils. Importantly, fecal transfer from control to antibiotic-exposed newborns restored normal pulmonary neutrophil responses, showing that the commensal microbiota is sufficient to program pulmonary immunity (open full item for complete abstract)

Committee: Hitesh Deshmukh M.D. Ph.D. (Committee Chair); Matthew Alder (Committee Member); William Zacharias M.D. Ph.D. (Committee Member); Emily Miraldi Ph.D. (Committee Member); Sing Sing Way M.D. Ph.D. (Committee Member); Theresa Alenghat V.M.D. Ph.D. (Committee Member) Subjects: Immunology

Doctor of Philosophy, The Ohio State University, 2024, Environmental Science

Every occupied indoor environment, including spacecraft, has its own unique microbiome. This composition and quantity of the microbiome present in these environments is dependent on many factors including building materials, occupants cleaning habits, presence of pets, and environmental conditions inside. Indoor microbes can be found in dust, which is generated in both Earth- and space-based built environments, a unique nutrient rich substrate that can act as both a source and sink especially in Earth-based buildings with carpet. Unintended microbial growth indoors can affect the health of the occupants and cause premature failure of building materials via biodegradation. Water is the limiting factor for growth, with moisture in the indoor air sufficient to support microbial growth indoors, especially for fungi. However, we need an improved understanding of microbes and their growth in indoor spaces to ensure healthier environments. The goal of this paper is to provide these examples and show how they fit into the concepts of One Space and bioastronautics. One Space is the idea that the built environment and human health are interconnected based on the One Health principles. Bioastronautics is the study of living organisms in spaceflight conditions. These two ideas complement each other and provide ample opportunity for interdisciplinary collaborations that can lead to innovative solutions to making healthier, safer, and more comfortable built environments on Earth and in space. In these studies, we focus on the intersection between microbiology and the built environment, by looking at the indoor dust microbiome in Earth- and space-based built environments like the International Space Station (ISS). We show that bacteriophages in common Earth-based building materials such as carpet and house dust can remain viable and infectious for up to several days making it a potential source of exposure. We also found the viral genetic material (RNA) remained stable for weeks t (open full item for complete abstract)

Committee: Karen Dannemiller (Advisor); John Horack (Committee Member); Michael Bisesi (Committee Member); Natalie Hull (Committee Member) Subjects: Environmental Health; Environmental Science; Microbiology