Impact of Environmental Exposures on the Microbiome and Human Health

Jack Gilbert, Ph.D.

Title

Human Health and Environmental Exposures During a Pandemic

Abstract

The microbiology, including bacteria and fungi, of our built environment can have significant influences on our health in myriad ways, from disease burden to health promotion. However, we are only just starting to characterize many of these mechanisms. Through detailed investigation of the bacteria and fungi that inhabit our homes, hospitals, offices and the environment around us, we have built up a global map that can be used to discover novel ways of manipulating these microbial communities to promote human health and reduce disease. We have quantified the degree of impact and speed of contamination of the human microbiome in our indoor environments, the influence of pet microbes on our homes and health, and the point sources of the microbiota found in our air and water that can exacerbate diseases such as asthma and cancer. These analyses are manifold, and comprehensively integrated with building and urban science to appropriately capture the physical, chemical and biological variables that influence the colonization, succession and function of the urban microbiome. Through new sensors and sophisticated molecular detection tools we have designed novel interventions to reduce antibiotic resistance and virulence of bacteria that survive in our buildings. We have also recently demonstrated that SARS-CoV-2 can bind to built environment associated bacteria, which potentially influences transmission. These interventions could revolutionize how buildings are designed, built and maintained.

Brief Biography

Jack A. Gilbert, Ph.D., earned his degree from Unilever and Nottingham University, United Kingdom in 2002, and received his postdoctoral training at Queens University, Canada. From 2005-2010 he was a senior scientist at Plymouth Marine Laboratory, United Kingdom; and from 2010-2018 he was Group Leader for Microbial Ecology at Argonne National Laboratory, a Professor of Surgery, and Director of the Microbiome Center at University of Chicago. In 2019 he moved to University of California San Diego, where he is a Professor in Pediatrics and the Scripps Institution of Oceanography. He uses molecular analysis to test fundamental hypotheses in microbial ecology. He cofounded the Earth Microbiome Project and American Gut Project. He has authored more than 300 peer reviewed publications and book chapters on microbial ecology. He is the founding Editor in Chief of mSystems journal. In 2014 he was recognized on Crain's Business Chicago's 40 Under 40 List, and in 2015 he was listed as one of the 50 most influential scientists by Business Insider, and in the Brilliant Ten by Popular Scientist. In 2016 he won the Altemeier Prize from the Surgical Infection Society, and the WH Pierce Prize from the Society for Applied Microbiology for research excellence. In 2019 he was elected to the Philosophical Society of Washington. He also co-authored "Dirt is Good" published in 2017, a popular science guide to the microbiome and children's health. He founded BiomeSense Inc in 2018 to produce automated microbiome sensors.

Tanya Alderete, Ph.D., Assistant Professor, University of Colorado Boulder

Title

Environmental Exposures and the Human Gut Microbiome: Implications for Obesity and Type 2 Diabetes

Abstract

Environmentally driven perturbations to the gut microbiome are involved in the development and progression of human disease, suggesting that the microbiome plays an intimate role at the interface between human health and the environment. Previous studies, including our own, have shown that exposure to air pollutants and perfluoroalkyl substances (PFAS) are associated with increased risk for obesity and type 2 diabetes. While the exact mechanisms underlying these relationships remain uncertain, animal studies suggest that these environmental toxicants adversely impact the gut microbiome. Our early findings indicate that exposure to air pollutants and perfluorooctanoic acid (PFOA) is associated with the newborn gut microbiota, which predicts rapid infant growth. Among young adults, our work has also shown that exposure to air pollutants is associated with glucose dysregulation, lower gut bacterial diversity, and enrichment of multiple gene pathways. These findings suggest that environmental exposures may impact the compositional and functional profile of the human gut microbiome across the life course, which has the potential to contribute to obesity and type 2 diabetes risk.

Brief Biography

Tanya L. Alderete, Ph.D., is an Assistant Professor at the University of Colorado Boulder in the Department of Integrative Physiology. She fuses clinical research with epidemiological approaches to evaluate the contribution of environmental exposures to the development of disease. Her research includes some of the first investigations to show that exposure to near-roadway and ambient air pollution contributes to the pathophysiology of type 2 diabetes in youth. Her laboratory is currently investigating the influence of exposure to air pollution on the composition and function of the human gut microbiome.

Stavros Garantziotis, M.D., Medical Director, National Institute of Environmental Health Sciences Clinical Research Unit

Title

Innate Immune Receptor TLR5 Protects Against Pulmonary Fibrosis Via Effects on the Microbiome

Abstract

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease resulting from maladaptive responses to lung epithelial injury. Epithelial homeostasis is promoted by activation of innate immunity by the microbiome. Here, we show that deficiency in the innate immune receptor TLR5 is associated with IPF in humans, and increased susceptibility to epithelial injury and experimental fibrosis in mice, while activation of lung epithelial TLR5 through a synthetic flagellin analogue induces antimicrobial gene expression and protects from experimental fibrosis. TLR5 deficiency in mice and IPF patients is associated with dysbiosis while TLR5 activation ameliorates dysbiosis similar to antibiotic treatment. Elimination of the microbiome through antibiotics abolishes the protective effect of TLR5 and reconstitution of the microbiome rescues the observed phenotype. In aggregate, our data suggest that TLR5 protects from epithelial injury and pulmonary fibrosis in humans and mice, and this protection is mediated by TLR5 effects on the microbiome.

Brief Biography

Stavros Garantziotis, M.D., is Medical Director of the National Institute of Environmental Health Sciences Clinical Research Unit (CRU), and Principal Investigator in the Immunity, Inflammation and Disease laboratory at the National Institute of Environmental Health Sciences. His research has focused on the role of innate immunity in the response to lung injury. Recently, his lab discovered a role in environmental lung injury for immune receptor TLR5, which recognizes the bacterial protein flagellin. Through this insight his lab was able to uncover an important role for the microbiome in lung injury and specifically pulmonary fibrosis and emphysema. Our research suggests that a healthy microbiome promotes lung health and protects against the development of emphysema and pulmonary fibrosis. Excitingly, we may be able to distill the microbiome effect down to single proteins, that can be then given to patients as treatment. We have partnered with a company to pursue this goal and are looking forward to translating our basic insights into the clinic.

Curtis Huttenhower, Ph.D., Professor, Harvard School of Public Health

Title

Microbial Toxicology in and Around the Human Body

Abstract

The degree to which the human microbiome modulates environmental toxicants is not yet clear, but two of the mechanisms by which it can do so include 1) direct metabolism of chemical compounds by microbes in and on the body, and 2) transfer of microbes via environmental intermediates that, while not themselves pathogens, can subsequently influence health outcomes. For the former, I will describe the Human Microbiome Bioactives Resource (HMBR), a platform for discovery and characterization of many types of microbiome bioactive products, including small molecule metabolites and microbial proteins. For the latter, we have investigated several mechanisms by which viable microbes and microbial genetic material can be transferred between human hosts and the environment, and I will describe assays for characterizing these with different degrees of accuracy (propidium monoazide or PMA staining, rRNA - not rRNA gene - amplicons, and protein-coding mRNA amplicons).

Brief Biography

Curtis Huttenhower, Ph.D., is a Professor of Computational Biology and Bioinformatics in the Departments of Biostatistics and Immunology and Infectious Diseases at the Harvard T.H. Chan School of Public Health, where he co-directs the Harvard Chan Microbiome in Public Health Center. He is an Associate Member at the Broad Institute's Microbiome Program. His lab focuses on computational methods for functional analysis of microbial communities and molecular epidemiology of the human microbiome. This includes systems biology reconstructions integrating metagenomic, metatranscriptomic, and other microbial community 'omics, the microbiome in diseases such as colorectal cancer, and its potential as a diagnostic tool and point of therapeutic intervention.

Yu Chen, Ph.D., Professor, New York University Grossman School of Medicine

Title

Arsenic Exposure, Gut Microbiome, and Carotid Intima-media Thickness in a Bangladesh Population

Abstract

Emerging data suggest that inorganic arsenic exposure and gut microbiome are associated with the risk of cardiovascular disease. To examine the inter-relationships between arsenic exposure, the gut microbiome, and carotid intima-media thickness (IMT)-a surrogate marker for atherosclerosis, we recruited 250 participants from the Health Effects of Arsenic Longitudinal Study in Bangladesh, measured IMT and collected fecal samples in year 2015-2016, and conducted 16S rRNA gene sequencing of microbial DNA extracted from the fecal samples. We also assessed association of anthropometric measures and cigarette smoking with gut microbiome profile. We found that higher BMI, mid-upper arm circumference, waist circumference, and waist-to-hip ratio were associated with a lower alpha diversity of fecal bacteria. Relative abundance of the genus Oscillospira and the family S24-7 were inversely related to all measurements after correction for multiple testing. The relative abundance of bacterial taxa along the Erysipelotrichi-to-Catenibacterium lineage was significantly higher in current smokers compared to never-smokers. We identified nominally significant associations between arsenic exposure, measured using either time-weighted water arsenic or urinary arsenic, and the relative abundances of several bacterial taxa from the phylum Tenericutes, Proteobacteria, and Firmicutes. Every 1% increase in the relative abundance of Aeromonadaceae and Citrobacter was related to an 18.2-?m (95% CI: 7.8, 28.5) and 97.3-?m (95% CI: 42.3, 152.3) difference in IMT, respectively. There was a significant interaction between Citrobacter and time-weighted water arsenic in IMT (P for interaction = 0.04).

Brief Biography

Yu Chen, Ph.D., is a chronic disease epidemiologist involved in multidisciplinary research that focuses on how host and environmental factors are related to chronic diseases, including cardiovascular disease and cancer. For the past 20 years, she has worked with colleagues from Columbia University and the University of Chicago to study health effects of arsenic exposure in the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh. She has conducted a series of studies on associations of arsenic exposure with cardiovascular disease-related outcomes. She has also investigated the interaction of arsenic exposure with other risk factors including gut microbiome. She is currently leading a project with colleagues at Vanderbilt University to investigate the role of the gastric and oral microbiome in gastric premalignant and malignant lesions. She is also a multiple PI for the New York University Women's Health Study, an NCI-funded prospective cohort study of more than 14,000 recruited since 1985. She is a recipient of the Outstanding New Environmental Scientist Award from the National Institute of Environmental Health Sciences. She is the Graduate Advisor for the Epidemiology PhD Program at New York University Vilcek Institute of Graduate Biomedical Science. She directs a course on epidemiology methods for PhD students. She received PhD with distinction in epidemiology from Columbia University in 2005. As of 2020, she has authored 199 journal articles.

Kun Lu, Ph.D., Associate Professor, University of North Carolina Gillings School of Global Public Health

Title

Decipher Signaling Molecules of Gut Microbiome Toxicity: Mechanism, Biomarker, and Intervention

Abstract

Accumulating evidence demonstrates that environmental chemicals can perturbs the gut microbiota by altering community structures, which becomes a new angle to evaluate the toxic effects of environmental toxicants. Modulation of the gut microbiome is also regarded as a promising approach to mediate exposure-associated human diseases. However, how exposure, microbiome and host interact at the molecular level, especially chemical signaling involved, remains a significant gap. This not only impedes mechanistic understanding how altered gut microbiome causes or contributes to disease, but also prevents mechanistic-based microbiome modulation to reduce adverse outcomes from exposure. With multi-omics, we have demonstrated significant changes in signaling molecules between conventionally raised animals and germ free mice, and environmental chemicals induced different toxicological responses in mice with different gut microbiome. We also demonstrated that exposure-altered gut microbiome causatively leads to disease in animals, such as diabetes. Likewise, using arsenic and perfluorooctanoic acid (PFOA) as examples, we have shown how the gut microbiome cross-talks with the host through microbiome-regulated signaling molecules, including bile acids and neuroactive metabolites. Deciphering microbiome-mediated chemical signaling and involved host signaling pathways provides important research avenues to understand molecular mechanisms underlying exposure-gut microbiome-host interactions, develop suitable biomarkers of gut microbiome toxicity and design microbiome-based intervention to reduce exposure induced diseases.

Brief Biography

Kun Lu, Ph.D., is an associate professor in the Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill. He is the Director of University of North Carolina Biomarker Mass Spectrometry Facility. The overarching goal of his research is to better understand health effects of environmental exposure and individual response. He has strong technical background and expertise in analytical chemistry, microbiome, exposome, and biomarker development. His lab works on numerous important environmental chemicals ranging from formaldehyde, heavy metals to pesticides, as well as others with significant public health concerns. One of his research thrusts is to develop DNA/protein adduct biomarkers and sensitive mass spectrometry assays to understand the carcinogenicity of chemicals and their risk assessment. He also studies how gut microbiome interacts with environmental exposure, how microbiome affects disease susceptibility, and how host factors crosstalk with microbiome to influence its response. Another focus of his research is to map exposome for human disease to characterize exposures via high-resolution mass spectrometry, understand the health impact of the exposome, and to design strategies to reduce exposure-associated adverse effects.

Julia Yue Cui, Ph.D., Associate Professor, University of Washington

Title

Interactions Between Gut Microbiome and Host PXR During Pathophysiological and Toxicological Conditions

Abstract

PXR is a liver-enriched receptor that contributes to xenobiotic biotransformation and nutrient homeostasis. Gut microbiome modifies the host hepatic signaling through remote-sensing mechanisms. We unveiled novel interactions between gut microbiome and host PXR signaling under pathophysiological and toxicological conditions. Under basal conditions, the absence of PXR increased the microbial richness and the pro-inflammatory Helicobacteraceae and Helicobacter. PXR enhanced high fat diet-induced body weight gain, hepatic steatosis, and inflammation especially in males. PXR is necessary in up-regulating pro-inflammatory cytokines and microbial response-related genes in livers of males. PXR is also necessary in promoting the increase in Firmicutes/Bacteroides ratio (a hallmark of obesity), the decrease in the anti-obesity Allobaculum and the anti-inflammatory Bifidobacterum, as well as the increase in the pro-inflammatory Lactobacillus, all in a male-specific manner. The dependency of gut microbiome on hepatic PXR-signaling was demonstrated using ChIP-Seq of PXR and H3K4me2 (a permissive epigenetic mark) in germ-free mice. Persistent environmental pollutants such as the formerly used flame-retardants PBDEs have caused safety concerns due to their bio-accumulative nature. Under toxicological conditions, we demonstrated that early life exposure to the known PXR-activator BDE-99 produced persistent gut dysbiosis and hepatic transcriptome towards a more cancer-prone signature in adult male pups. BDE-99 up-regulated the short chain fatty acid-producing Akkermansia muciniphila, corresponding to a persistent up-regulation of several SCFAs and reprogrammed epigenetic landscape in adult livers. In conclusion, the gut microbiome is critical in modulating the host PXR signaling both acutely and persistently, and participates in both the acute chemical toxicity and developmental reprogramming.

Brief Biography

Julia Yue Cui, Ph.D., is a Sheldon Murphy-endowed Associate Professor at Department of Environmental and Occupational Health Sciences at University of Washington. Julia's research is in areas of early life exposure to environmental chemicals, gut microbiome, and epigenetic reprogramming of the developmental trajectory in liver. Her research is currently supported by 2 National Institute of Environmental Health Sciences R01 grants and the Sheldon Murphy Endowment. Julia received her PhD degree in Toxicology from University of Kansas Medical Center under the mentorship of Dr. Curtis D. Klaassen in 2010. She has published 67 peer-reviewed manuscripts and 3 book chapters. She received 19 research awards from Society of Toxicology (SOT) and other scientific societies, and she serves as the President of the Pacific Northwest SOT Regional Chapter.

Andrew Patterson, Ph.D., Professor, Pennsylvania State University

Title

A Microbiome Perspective of Environmental Chemical Toxicity

Abstract

The fields of drug metabolism, pharmacology, and toxicology have long suggested that host microbiota could influence the disposition and toxicity of xenobiotics. Pioneering work with azo dyes pointed towards the necessity to not only understand the metabolic capabilities of the microbiota, but to identify the specific microbes contributing to xenobiotic metabolism. Early correlative studies of heavy metal exposure identified the microbiota as contributing to the host toxicity. However, technological limitations necessary for cataloging the microbiota community structure and for characterizing their metabolic capabilities have hitherto hindered progress in this area. Recent technological advances including sequence-based identification and functional characterization via mass spectrometry-based metabolite profiling have begun to shed light on how microbes influence and/or impact xenobiotic metabolism and toxicity. The ability to reconstitute specific bacteria in the gut and study their effects on drug metabolism and toxicity has become feasible. Data will be presented to highlight key aspects of gut microbiota-drug interaction, including microbiota identification, metabolic function and prediction, metabolite identification and profiling, which have expanded our understanding of the interaction of xenobiotics with the microbiome. Lastly, a perspective of the future of this field will be presented taking into account what important knowledge is lacking and how to tackle these problems with respect to informing exposure, human health, and disease risk.

Brief Biography

Andrew Patterson, Ph.D., is the Tombros Early Career Professor and Professor of Molecular Toxicology at the Pennsylvania State University, University Park, PA and is the Scientific Director of Metabolomics. He holds joint appointments in the Department of Veterinary and Biomedical Sciences and the Department of Biochemistry and Molecular Biology. He and his students, postdocs, and collaborators focus on understanding the host-metabolite-microbiota communication network-specifically how the manipulation of gut microbiota by diet and/or xenobiotics impacts host metabolites (e.g., bile acids, short chain fatty acids), their metabolism, and how these co-metabolites interact with host ligand-activated transcription factors. The lab employs a variety of tools, including NMR- and mass spectrometry-based metabolomics, genomics, and conventional and gnotobiotic transgenic mice, to facilitate its study of these pathways and understand their impact on human health and disease.

Andrew Goodman, Ph.D., Professor, Yale University

Title

Microbiome Contributions to Drug Metabolism

Abstract

Oral medicinal drugs can exhibit incomplete absorption in the upper gastrointestinal tract or reach the gut after enterohepatic circulation. In these circumstances, drugs encounter enormous densities of commensal microbes. These microbes collectively encode 150-fold more genes than the human genome, including a rich repository of enzymes with the potential to metabolize drugs. However, the contribution of the microbiome to drug and drug metabolite exposure in the GI tract and in circulation is largely unexplored.

I will describe examples that suggest that gut microbial activity can be responsible for a significant portion of systemic exposure to a toxic drug metabolite, even if the drug exhibits high bioavailability, if the same metabolite is readily produced by hepatic extracts in vitro, and if drug metabolite levels are low in feces. I will also introduce our efforts to explore the spectrum of microbiome-encoded drug metabolizing activities and to identify microbial genes that predict the capacity of an individual's gut microbiome to metabolize a drug.

Brief Biography

Andrew L. Goodman, Ph.D., is the C. N. H. Long Professor of Microbial Pathogenesis at Yale University School of Medicine and Director of the Yale University Microbial Sciences Institute. Goodman received his undergraduate degree in Ecology and Evolutionary Biology from Princeton University, his PhD in Microbiology and Molecular Genetics from Harvard University, and completed postdoctoral training at Washington University. His lab uses microbial genetics, gnotobiotics, and mass spectrometry to understand how the gut microbiome contributes to drug metabolism. The Goodman lab works to identify and characterize microbiome-encoded drug metabolizing enzymes, and to define how these microbial activities contribute to drug and drug metabolite exposure in the gut and in circulation. The lab's contributions have been recognized by the National Institutes of Health Director New Innovator Award, the Pew Foundation, the Dupont Young Professors Award, the Burroughs Wellcome Foundation, the Howard Hughes Medical Institute Faculty Scholars Program, the ASPET John J. Abel Award, and the Presidential Early Career Award in Science and Engineering.

Mohamed Abou Donia, Ph.D., Associate Professor, Princeton University

Title

Personalized Mapping of Drug Metabolism by the Human Gut Microbiome

Abstract

The human microbiome affects several aspects of human health, disease, and response to therapy, but the molecular mechanisms by which it exerts these effects are largely unknown. In this talk, we will describe our efforts to systematically map the capacity of the human gut microbiome to metabolize hundreds of orally administered medications in a personalized manner, and to characterize the genes responsible for the observed metabolism and the metabolites resulting from it.

Brief Biography

Mohamed Abou Donia, Ph.D., received his BSc in Pharmacy from the Faculty of Pharmacy, Suez Canal University, Egypt in 2004. He moved to the US in 2005 to study for his PhD at the Medicinal Chemistry Department, School of Pharmacy, University of Utah. He worked in the laboratory of Eric Schmidt, Ph.D., where he studied the chemistry and biology of small molecules produced by bacterial symbionts of marine animals. He used chemical, microbiological, and metagenomic techniques to study the role of small molecules in mediating microbe-host and microbe-microbe interactions in marine invertebrates. In 2010, he joined the laboratory of Michael Fischbach, Ph.D., at the Department of Bioengineering and Therapeutic Sciences at the University of California, San Francisco. There, he studied small molecules produced by members of the human microbiome and their role in mediating microbe-host and microbe-microbe interactions in humans. In particular, he focused on antibiotics produced by human pathogens and commensals, and their role in shaping the composition and dynamics of the human vaginal and oral microbiota. Mohamed Abou Donia, Ph.D., is a recipient of the NIH Director's New Innovator Award, the Kenneth Rainin Foundation Innovation and Breakthrough Awards, and is named a Pew Biomedical Scholar.

Aaron Wright, Ph.D., Senior Biomedical Scientist, Pacific Northwest National Laboratory

Title

Phenotype-driven Profiling of the Gut Microbiome

Abstract

The current understanding of the functional activity of host-associated microbial communities is primarily based on comparative metagenomic and metatranscriptomic studies. This data is important but is a poor predictor of how communities function and how they respond to perturbations such as chemical exposures, emergent pollutants, diet, and disease. Genome and transcriptome studies can identify the potential for a specific function but cannot demonstrate that a function is present and active, nor can it demonstrate that any given microbe is responsible for a given function. We are developing new phenotype-based approaches that rely on synthetic chemical probes for profiling drug and xenobiotic metabolism and carbohydrate metabolism within the gut microbiome and host tissues. Our probes are multimodal, such that the reporting of protein binding events can be readily varied resulting in a versatile functional measurement platform that can be used for imaging, fluorescence-activated cell sorting followed by DNA sequencing, and proteomics. Using our phenotype-driven approach we are quantifying phase I and II enzyme activities in the liver, lung, and intestine. Within the gut microbiome we are characterizing and quantifying the role of microbes and their enzymes in drug, toxin, and carbohydrate metabolism. In both the host and microbiome we are also characterizing how environmental, drug, and chemical exposures impact these activities. The approach we're taking with chemical probes is enabling a much improved function understanding of the host and microbial communities.

Brief Biography

Aaron Wright, Ph.D., is a principal investigator in Chemical Biology and director of the Biological Systems Science Group in the Biological Sciences Division at Pacific Northwest National Laboratory. He also holds a joint appointment as a research professor in the Gene and Linda Voiland School of Chemical Engineering and Bioengineering at Washington State University. His research group is focused on phenotype profiling using synthetic organic chemistry to develop chemical probes that when deployed in living systems enable a much improved functional and mechanistic understanding of biochemical processes. His group is active in the following research areas: (a) spatiotemporal, functional, and interaction dynamics of microbes within microbiomes; (b) oxidative and conjugative metabolism in mammalian liver and lung, particularly with regard to environmental exposures and development; and, (c) the relationship between host metabolism and the gut microbiome. His research is providing a phenotype profiling platform for future studies that evaluate individual variability and susceptibility to diseases, to understand consequences associated with xenobiotic exposures in adults and developing children, and for the future of precision medicine.

Scott Jackson, Ph.D., Scientist at the National Institute of Standards and Technology

Title

Standards to Support Innovation and Translation of Microbiome Science

Abstract

Appreciation for the role of microbes in our lives has been growing rapidly, but the measurement science needed to understand and fully exploit microbial systems has developed at a much slower pace than the industries dependent on them demand. The National Institute of Standards and Technology is developing standards for microbiome measurements that will enable federal, academic, and industry labs to reliably reproduce and advance each other's results. Microbiome standards will support research investigations and commercial translation of microbiome science by providing measurement assurance tools including reference materials, validated measurements, interlab studies, and critically evaluated reference data.

Brief Biography

Scott Jackson, Ph.D., joined the National Institute of Standards and Technology (NIST) in May of 2014. There, he is currently the leader of the Complex Microbial Systems Group in the Biosystems and Biomaterials Division. In this current role, he is leading international efforts to improve microbiome and metagenomic measurements by organizing inter-lab studies, developing reference materials and reference methods, and developing in vitro tools that allow us to better understand microbial community resilience and evolution. Prior to joining the National Institute of Standards and Technology in 2014, he spent 11 years as a principal investigator with the Food and Drug Administration where his research focused on understanding the global genomic diversity of enteric pathogens.

Gail Rosen, Ph.D., Professor, Drexel University

Title

Benchmarking Efforts for Performance and Scalability of Metagenomic Taxonomic Classifiers

Abstract

Two important components of the microbiome are the community structure and function. The first step in many metagenomics pipelines is to identify the taxa present in each sample to decipher this structure. Errors on this first step can propagate to other downstream analyses, thus it is important to benchmark methods on this step. While there are many methods for taxonomic classification, there are very few benchmarks and comparisons between these techniques. In this presentation, we will survey benchmarking efforts, notable measures of performance, and their advantages and disadvantages. Furthermore, we will discuss how methods may scale with increasing databases and datasets and pose a challenge to the future of the field.

Brief Biography

Gail Rosen received a BS, MS, and PhD from the Georgia Institute of Technology. She is a recipient of an NSF CAREER award, a Drexel Faculty Career Development award, and a Louis and Bessie Stein Fellowship award. She serves on the editorial boards of ASM mSystems and BMC Microbiome journal and has attended two NSF-NIH BD2K Innovation Labs on Quantitative Approaches to Biomedical Data Science. She heads the Ecological and Evolutionary Signal-processing and Informatics (EESI) lab and organizes the Center for Biological Discovery from Big Data. In 2015-2016, she spent a year as a visiting scholar at Weill Cornell Medicine, developing benchmarks for taxonomic classification and analyzing the ambulance microbiome. Her interests are in machine learning and evolution.

Shyamal Peddada, Ph.D., Senior Investigator, National Institute of Child Health and Human Development, National Institutes of Health

Title

Differential Abundance Analysis of Microbiome Data With Applications

Abstract

A major challenge with high throughput count data, such as the microbiome or the RNA-seq data, is normalization. It is well-known from empirical studies published in the literature that poor normalization of such data may lead to inflated false discovery rates. As demonstrated in recent literature, in some situations the expected false discovery rates for microbiome data can be as high as 60% for poorly normalized data. Thus, 60 out 100 taxa discovered as differentially abundant are false positives. In this talk we shall describe a recently developed methodology called ANCOM-BC (Lin and Peddada, Nature Comm., 2020) and illustrate the methodology using an oral microbiome data (Yetsunenko, Nature 2012).

Brief Biography

Shyamal Peddada, Ph.D., is a Senior Investigator and the Chief of Biostatistics and Bioinformatics Branch, NICHD. Previous positions held by him include professor and Chair of Department of Biostatistics, University of Pittsburgh and Senior Investigator and Acting Chief of Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences and Professor of Statistics, Department of Statistics, University of Virginia. He is a fellow of the American Statistical Association, and the International Statistical Institute. He is an expert in Constrained Statistical Inference and methods for analysis of microbiome data. The ANCOM methodology, which was developed while he was at National Institute of Environmental Health Sciences, is available through the QIIME2 software and is widely used for analyzing microbiome data.

Sarah Rothenberg, Ph.D.

Title

Longitudinal Changes During Pregnancy in Gut Microbiota and Methylmercury Biomarkers

Abstract

Our main objective was to investigate whether associations between biomarkers for prenatal methylmercury (MeHg) exposure and maternal gut microbiota differed between early and late gestation. Methods: Maternal blood and stool samples were collected during early (8.3–17 weeks, n=28) and late (27–36 weeks, n=24) gestation. Total mercury and MeHg concentrations were quantified in biomarkers. The diversity and structure of the gut microbiota were investigated using 16S rRNA gene profiling. Biomarkers were dichotomized, and diversity patterns were compared between high/low mercury concentrations. Spearman's correlation was used to assess bivariate associations between MeHg biomarkers, and 23 gut microbial taxa (genus or family level, > 1% average relative abundance). Results: Within-person and between-person diversity patterns in gut microbiota differed between early/late gestation. The overall composition of the microbiome differed between high/low MeHg concentrations (in blood and stool) during early gestation, but not late gestation. Ten (of 23) taxa were significantly correlated with MeHg biomarkers (increasing or decreasing); however, associations differed, depending on whether the sample was collected during early or late gestation. A total of 43% of associations (69/161) reversed the direction of correlation between early/late gestation. Conclusions: The time point at which a maternal fecal sample is collected may yield different associations between gut microorganisms and MeHg biomarkers, which may be due in part to remodeling of maternal microbiota during pregnancy. Our results suggest the effectiveness of dietary interventions to reduce prenatal MeHg exposure may differ between early and late gestation.

Caroline Smith, Ph.D.

Title

Impact of Exposure to Air Pollution and Maternal Stress on the Gut Microbiome and Social Brain

Abstract

Autism spectrum disorder (ASD) currently affects 1 in 59 children in the United States, 80% of whom are male, and is characterized primarily by impaired social interaction/communication. Prenatal exposure to air pollution has been implicated in the etiology of ASD, as well as many other neuropsychiatric disorders. Importantly, there are large social disparities in environmental toxin exposure whereby marginalized communities bear the greatest burden of exposure. Using a novel mouse model that combines an environmental toxin (diesel exhaust particles; DEP) with an ethologically relevant maternal stressor (resource deprivation; MS) during pregnancy, we find that these exposures in combination, but neither alone, induce robust deficits in social interaction in male, but not female offspring. ASD is increasingly recognized as a whole-body disorder and changes in the gut microbiome have been observed in multiple human studies of ASD, as well as in animal models. We find that combined DEP/MS exposure induces robust changes in the composition of the gut microbiome in males only. Furthermore, we observe changes in the structure and gene expression of the intestinal epithelium. Finally, manipulations that restore the composition of the gut microbiome, including cross-fostering to a naive dam at birth and co-housing with naive cage mates at weaning, restore social behavior in our model. Together, these findings suggest a causal contribution of the gut microbiome to social behavior deficits following DEP/MS exposure.

Ian Myles, M.D.,MPH

Title

Assessing the Effects of Common Topical Exposures on Skin Bacteria Associated with Atopic Dermatitis

Abstract

To date, nearly all the studies into the skin microbiome have been informed by protocols which have asked participants to avoid topical products (such as soaps or select medications) for the preceding days to weeks prior to sample collection. We have recently reported the therapeutic potential of the healthy skin commensal Roseomonas mucosa for patients with atopic dermatitis involves lipid-mediated TNF-associated repair pathways. Herein we assess environmental exposures which may bolster or hinder the microorganisms that influence these pathways. We expanded our previous evaluations to test the toxicological effects of a broader range of common chemicals, AD treatments, and lotions using both health- and disease-associated strains of R. mucosa and Staphylococcus spp. Numerous topical exposures possessed anti-microbial properties, including many that are not marketed as antibiotics. Through targeted combination of potentially beneficial chemicals, we were able to identify a combination which promoted the growth of health associated isolates over disease associated strains both in vitro and using the dermatologic patch exposure on a small number of healthy volunteers. The results of this investigation may better inform the AD patient population on which products to use and guide formulation of new topicals that may offer benefit patients with AD.

Elise Hickman

Title

Effects of Sex, E-cigarette, & Cigarette Use on the Nasal Microbiome & Host-microbiota Interactions

Abstract

The effects of e-cigarettes on the respiratory system have not been fully characterized, including the effects on the respiratory microbiome. The respiratory microbiome plays a key role in respiratory host defense, and respiratory microbiome dysbiosis has been associated with diseases such as asthma, chronic obstructive pulmonary disease, chronic rhinosinusitis, and cystic fibrosis, as well as with smoking cigarettes. To determine whether e-cigarette use causes respiratory microbiome dysbiosis, we performed 16S rRNA gene sequencing on nasal epithelial lining fluid collected from e-cigarette users, smokers, and non-smokers using non-invasive absorptive strips. We also analyzed matched cell-free nasal lavage fluid samples for mediators of host-microbiota interaction. Our results indicate that e-cigarette use can alter the nasal microbiome and mediators of host-microbiota interaction and that this alteration is different from the dysbiosis observed in association with cigarette use. This disruption of respiratory mucosal immune responses in e-cigarette users may mean that they have increased susceptibility to infection by specific bacterial taxa. We also observed a significant effect of sex on the nasal microbiome, highlighting the importance of including sex as a biological variable in nasal microbiome studies.

Martin Strazar

Title

Urbanization-driven Changes in the Gut Microbiota Reveal Immunomodulatory Metabolites and Pathways

Abstract

The human immune system maintains constant intestinal homeostasis through sensing microbial ligands and metabolites. The discovery of novel immunomodulatory factors in healthy human cohorts is challenging due to the vast number of circulating metabolites, underexplored microbial variation and limited opportunities for controlled interventions. We present a large cohort from urban and rural Tanzania, which reflects rapid urbanization, migration and related lifestyle changes. This urbanization gradient is reflected in stool metagenomes and reveals a loss of Bacteroidetes, notably Prevotella copri, and an increase in Firmicutes and Verrucomicrobia, including Bifidobacterium longum and Akkermansia muciniphila, which are more common in Western European populations. These environmental shifts persist in circulating metabolites of dietary and microbial origin. The subjects from urban areas also show elevated levels of ex vivo cytokine expression, including TNF-α and IFN-γ, in responses to multiple bacterial and fungal stimuli. The observed large cohort variation provides the necessary statistical power to detect 34 immunomodulatory microbes, while an integrative analysis allows us to separate microbial and host effects on the metabolome. Multiple lines of evidence, from pathway effects on cytokines, differential metabolome analysis, to enzyme family enrichment uncover that histidine and arginine metabolism compounds are mediated by B. longum, A. muciniphila and other immunomodulatory microbes. The discovered compounds and pathways may aid understanding and investigating intestinal homeostasis as well as present potential therapeutic routes to modulate response to pathogen infections.

Min Hyung Ryu

Title

Effect of Exposure to Traffic-related Air Pollution Is Modified by Lung Microbiome

Abstract

Rationale. Human-microbial interaction is thought to be an important determinant of health and disease. Little is known about the influence of lung microbiome on the human host response to air pollution exposure. If the effects of air pollution exposure on airflow and airway cytokines are modified by airway microbiome diversity, as we hypothesize, this would support attempts to modify that diversity to benefit those inevitably exposed. Methods. Twenty-five participants in this randomized, double-blinded, crossover, controlled human exposure study to diesel exhaust (DE, paradigmatic of traffic-related air pollution) were included in this analysis. Each participant was exposed for 2 hours to DE and filtered air (FA; control) in random order with a 4-week washout. 24 hours after each exposure, bronchoscopy was performed to collect endobronchial brush and bronchoalveolar lavage (BAL). Microbial DNA was extracted from the endobronchial brush. PCR was performed to derive the V4 hypervariable amplicons of the 16S rRNA gene. Amplicons were sequenced using Illumina Miseq, and Qiime2 pipeline was used for the microbiome analyses. BAL was analyzed for cytokines using multiplex electrochemiluminescence. Statistical analysis was performed using linear mixed-effects models. Results. There was significant exposure-by-richness interaction on FEV1 (p=0.01) and interleukin (IL)-6 (p=0.03). Participants who had lower alpha diversity (values ≤ median of Richness) experienced greater airflow obstruction and an increase in IL-6 following the DE exposure compared to those with higher diversity (>median). In the low diversity group, DE significantly increased IL-6 (p=0.05), IL-7 (p=0.03), and IL-15 (p=0.03) in BAL. In contrast, neither COPD status, ex-smoking status, nor age were effect modifiers. Conclusion. Individuals with low microbial diversity in the lower respiratory tract appear to be more susceptible to the harmful effects of air pollution.

Yan Yan, Ph.D.

Title

Identifying Strain-specific Functional Genes in Colorectal Cancer

Abstract

Changes in the gut microbiota have been associated with colorectal cancer (CRC), but neither the causal mechanisms nor corresponding microbial strains and small molecule products have been elucidated for CRC. We have developed a new strain-level meta-analysis using stool metagenomic profiles of 600 CRC patients, 143 with pre-cancerous adenomas, and 662 healthy controls from nine recently published CRC microbiome studies. We created the MMUPHin framework to jointly normalise these datasets and identify potential consistently significant links between CRC neoplasia, severity, and microbial species and strains. We identified several species as novel CRC biomarkers including several typical oral species. The clade with the greatest phylogenetic contribution to CRC was Prevotella copri, and since the species’ subclades are also highly geographically associated, this may suggest that there are regional contributions by P. copri subtypes to carcinogenesis. A group of functional genes unique to subsets of E. coli strains was associated with CRC phenotypes, comprising annotations to transporters, type II secretion systems, flagellar and sulfur metabolism. This study adds further evidence to the hypothesis that strain-level genomic variation in gut microbes may be a major driver in the initiation or development of CRC.

Karen Dannemiller

Title

Fungal Communities in House Dust and Associations with Neighborhood Asthma Prevalence in the Naas Co

Abstract

Asthma development is inversely associated with indoor exposures to fungal diversity. However, we need to better understand if fungal diversity is similarly associated with measures of asthma morbidity and whether individual fungal species may disproportionately drive such relationships. We hypothesized that fungal diversity is inversely associated with neighborhood asthma prevalence and aimed to identify specific fungal species strongly associated with asthma morbidity. Bedroom dust samples were collected from the homes of children aged 7-10 years (n=349), living in low (3-9%) and high (11-18%) asthma prevalence neighborhoods in New York City. Fungal communities were analyzed using DNA-based methods. Neighborhood asthma prevalence was inversely associated with both fungal species richness (P=0.005) and Shannon diversity (P=0.01). Shannon diversity was inversely associated with asthma symptom frequency among children age 7-8 (OR 0.72, P=0.017). Species richness was inversely associated with asthma persistence to age 10-11 (OR 0.99, P=0.040). We did not identify individual fungal species significantly associated with measures of asthma morbidity once adjusting for false discovery rates. Increased asthma morbidity was associated with decreased fungal diversity, but not with individual fungal species, in this urban, pediatric cohort. Continued research is needed to better understand the many factors influencing indoor fungal exposures.

Juan Maestre, Ph.D.

Title

When Dust Settles: The Microbiome in Water Damaged Homes Following Hurricane Maria

Abstract

Microbial communities in 50 naturally ventilated households impacted by Hurricane Maria in Puerto Rico were studied for two years following the event (25 flooded -FH- and 25 non-flooded homes -NFH-). Samples were collected for culturable, molecular, and pro-inflammatory potential analyses, and health surveys applied. Fungal DNA was analyzed via high-throughput sequencing, and the pro-inflammatory potential (PIP) was assessed via ELISA quantification of the induced cytokine interleukin-1β in peripheral human blood.Indoor fungal spore concentrations were higher in FH than in NFH for both years (p < 0.01). Overall fungal community structure in the FH & NFH were not significantly different, though potentially pathogenic fungal genera such as Aspergillus species were enriched in FHs relative to outdoor controls and NFH; differences were observed in moisture-associated genera (Trichoderma, Aspergillus, Fusarium and Wallemia). In FH, damage to kitchen areas was associated with 1.2 (p = 0.009) and 2.35-fold (p = 0.03) increase in dust PIP. Flooding damage requiring repair was associated with statistically significant increases in dust PIP (p = 0.02 to 0.004). Results show that individuals living in FHs whose home’s dust had higher PIP, reported higher negative respiratory symptoms than NFH, for up to two years after Hurricane Maria.

Sarah Haines

Title

Microbial Growth Can Be Modeled in Carpet Dust

Abstract

Upwards of 4.6 million asthma cases can be attributed to exposure to mold and water dampness indoors. The resuspension of floor dust is an important source of bioaerosols contributing to human microbial exposures. Microbial growth in carpet dust occurs at elevated relative humidity (RH) levels (>80%). However, we do not understand how to model this growth or how moisture influences species composition. Therefore, we need a framework for modeling microbial growth in carpet dust. Carpet and dust were collected and incubated at varying RH conditions of 50%, 85% and 100% for either 6, 12, 18 or 24 hours. Fungal growth followed the two-activation regime model and location of collection was most important to species composition (P = 0.001, R2 = 0.461). Moisture however did contribute to species composition within each site. Fungal genera Aspergillus, Penicillium, and Wallemia were commonly found among samples at elevated moisture conditions. This may inform future indoor microbiome studies of associations between dampness and mold in housing as well as influence mold detection.

Scott Burchiel, Ph.D.

Title

Metagenomic Analysis of Mouse Fecal Bacteria Following Oral 45 Day Exposures to Uranium and Arsenite

Abstract

Previous studies by our labs have shown that arsenic and uranium exert significant immunotoxicity on the gastrointestinal tract of mice. Because metals are known to influence the bacterial microbiome and potential toxicity of metals, we conducted metagenomic analyses on fresh feces collected from male and female mice after 45 days of metal exposures. Our studies show that UA and As+3 alone or in combination, altered the microbiome alpha diversity in feces. In addition, a number of metal associated genes were altered and associated with specific bacterial species. The potential role of microbiota in modulating immunotoxicity of the gut immune system of mice will be discussed. This work was supported by NIEHS 1P42 ES025589.

Janielle Vidal

Title

Copper in Drinking Water Alters the Microbiome in a Happ Knock-in Mouse Model of Alzheimer's Disease

Abstract

Although copper is an essential metal, exposure to its free cupric form may exert toxicity and has been linked to Alzheimer's Disease. Copper is a natural antimicrobial which may perturb the gut microbiome. Recent studies implicate gut dysbiosis in the onset and progression of AD in both humans and animal models. We sought to determine if chronic exposure environmentally relevant doses of copper through drinking water will induce gut dysbiosis in humanized APPNL-G-F knock-in (hAPP-KI) mice and change host inflammatory profile. 3-month-old hAPP-KI and wildtype mice were exposed to copper in drinking water ad-libitum for 3 months. Fecal matter was sampled monthly and DNA was isolated for amplicon sequencing of the 16s rRNA V4 region. At sacrifice, blood and brain tissue were harvested for immunohistochemistry and biochemistry. Copper had no significant effect on the microbiota of wildtype mice. hAPP-KI mice had significant increases in S24-7 (Bacteroidetes) and decreases in Allobaculum (Firmicutes) respectively. No differences were seen in inflammation or AD pathology. The microbiome of hAPP-KI mice is thus less resilient to effects of copper compared to WT mice. Certain bacterial populations in the gut may be sensitive to environmental agents and longer exposures with older animals may elucidate associations to AD.

Russel Fling

Title

TCDD Elicits Changes in Microbiome Consistent with Progression of Non-alcoholic Fatty Liver Disease

Abstract

Gut dysbiosis and disrupted bile acid metabolism, commonly associated with the development and progression of non-alcoholic liver disease (NAFLD), is recapitulated in male mice exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). Previous work demonstrated TCDD increased serum levels of deoxycholic acid, a secondary bile acid produced by microbial metabolism exhibiting farnesoid X receptor antagonist activity. To investigate TCDD-elicited changes in the gut microbiota, male mice (n=3) were orally gavaged with sesame oil vehicle control or 0.3, 3 or 30 µg/kg TCDD every 4 days for 28 days. Shotgun metagenomic sequencing of cecum contents identified shifts in taxa and microbial metabolomic pathways. Many species including Turcibacter sanguinis and Lactobacillus reuteri which contain genes associated with bile salt hydrolases also exhibited dose-dependent increases. In addition, metagenomic functional analysis revealed TCDD enriched for species contributing to fermentation pathways which produce metabolites impacting NAFLD progression (i.e. acetate and alcohol). Our results suggest TCDD dose-dependently increased species capable of bile acid metabolism in response to altered bile acid levels and enriched microbial metabolic pathways relevant to NAFLD. RRF is supported by the NIEHS Multidisciplinary Training in Environmental Toxicology (NIEHS EHS T32ES007255). This work was funded by the NIEHS Superfund Research Program (NIEHS SRP P42ES04911), and NIEHS R01ES029541.

John Rawls, Ph.D.

Title

Tributyltin Exposure Promotes Adipose Tissue Accumulation by Reducing Leptogenic Bacteria

Abstract

The chemical obesogen tributyltin (TBT) is known to promote fat storage in adipose tissue through direct action on vertebrate cells. However, TBT also has direct toxic effects on microorganisms, raising the possibility that TBT may also promote fat storage by altering vertebrate microbiota composition. Here we show that chronic exposure of conventionally-reared zebrafish to TBT results in increased adiposity, reduced body size, and altered intestinal microbiota composition including reduced relative abundance of Plesiomonas bacteria. To test the ability of those microbiota alterations to affect host adiposity, we exposed conventionally-reared zebrafish to selected intestinal bacterial strains representative of taxa altered by TBT exposure. We found that colonization with a Plesiomonas strain was sufficient to reduce adiposity and alter gut microbiota composition. To distinguish between direct and indirect effects of Plesiomonas on the host, we developed and used a new long-term gnotobiotic zebrafish husbandry protocol to show that colonization of germ-free zebrafish with Plesiomonas alone was sufficient to reduce host adiposity. Together these results show Plesiomonas has leptogenic effects on zebrafish hosts, indicating the ability of TBT to increase adiposity in vivo may be due in part to TBT-mediated reductions in leptogenic bacteria like Plesiomonas. These findings underscore the complex reciprocal interactions that can occur between animals and their microbial and chemical environments to influence energy balance and metabolic health.

Yun-Chung Hsiao

Title

Piecing up the Cancer Potential Contributed by the Gut Microbiome: Biomarkers and Xenobiotic Metabolism

Abstract

There have been evidence supporting the association between the characteristics of the gut microbiome and cancer event. However, there is still insufficient knowledge on the mechanism of how the gut microbiome involves in carcinogenesis. The formation of DNA adducts are key events in cancer development. This presentation introduces my research on how the existence of gut microbiome can modulate levels of endogenous DNA adducts. Multiple DNA adducts related to host endogenous processes including lipid peroxidation, aberrant DNA alkylation were monitored between conventional-raised mice and germ-free mice, and we found significant different levels of specific species of DNA adducts. Our data suggests that the gut microbiome can impact cancer potential by modulating immune-response, lipid peroxidation, and aldehyde metabolism.

Ashutosh Mangalam, Ph.D.

Title

Effect of Exposure to the Herbicide Glyphosate on the Host Gut Microbiome and Systemic Inflammation

Abstract

The widespread use of glyphosate, a broad-spectrum herbicide has resulted in significant human exposure to glyphosate. Although the link between the disease state and glyphosate is increasingly appreciated, the mechanistic links between the glyphosate and its toxic effects on human health are unknown. Trillions of bacteria (microbiota) living in the human gut play an important role in health and disease. Therefore, we tested the hypothesis that glyphosate mediates its toxic effects through dose-dependent perturbation of gut microbiota resulting in gut dysbiosis and leaky gut which lead to low grade systemic inflammation. Detailed fecal microbiome analyses revealed that consumption of glyphosate caused dose dependent changes in the composition of the gut microbiota with a dose-dependent decrease in the relative abundance of Akkermansia muciniphila, Turicibacter, Enterorhabdus and Clostridium. Functional metabolic pathway analysis showed that exposure to glyphosate results in suppression of pathways responsible for maintaining the oxidative stress and SCFA production, both of which are associated with maintaining an anti-inflammatory state of the host. Glyphosate also increased number of pro-inflammatory mediators such as IL-12p70, CCL5, CXCL10, and CCL11/eotxin. Thus, our preliminary study suggest that glyphosate can cause adverse health effects through modulation of gut microbiota which then can promote systemic inflammation.

Vanessa Lopez

Title

Assessing the Impact of Benzalkonium Chlorides on Gut Microbiota

Abstract

Benzalkonium Chlorides (BACs) are widely used antimicrobial disinfectants in a variety of consumer and food processing settings. The prevalence of BACs raises concerns that exposure to BACs could disrupt the gastrointestinal microbiota, thus interfering with their beneficial functions to host health. The gut microbiota has been found to regulate the expression of drug metabolizing enzymes (DMEs). Disruption of the diversity and abundance of gut microbiota and subsequently, on the metabolic phenotype and DMEs by BACs provides a novel mechanism by which BACs can negatively impact human health. Previous studies have also shown that environmental agents can induce changes in the microbiota and subsequent changes on DME expression. Thus, we hypothesize that BACs can alter the gut microbiome, which can lead to changes in intestinal metabolome, DME expression, and bile acid (BA) homeostasis. First, I aim to characterize changes in the microbiome after BAC exposure by using 16S rRNA gene sequencing, as well as targeted and untargeted metabolomics and lipidomics. Second, I will assess changes in intestinal and hepatic DMEs using RNA sequencing and validate such changes using enzyme activity assays and in vivo drug-metabolism studies. Preliminary data suggests that BAC exposure alters microbiome composition and richness in mouse intestine; and leads to differentially expressed genes and upstream pathways in mouse livers. We expect this study to reveal new insights on alterations in the homeostasis between gut microbiome and liver by BACs.

Eliseo Castillo, Ph.D.

Title

Microplastics Alter the Gut Microbiota Through Changes in Cellular Metabolism

Abstract

Plastic pollution has become a global environmental problem that has led to the ingestion of microplastics. Given microplastics are being ingested it is critical to understand what effect this has on the gastrointestinal tract. Intestinal homeostasis and inflammation is balanced by the tripartite interaction between the gut microbiota, the immune system, and intestinal epithelium. Dysfunction in one of these components can have profound effects on the other two systems. Our studies demonstrate microplastic ingestion in mice alters the gut microbiota. We believe this alteration in the microbiota is due to changes in the cellular metabolism of macrophages and intestinal epithelial cells. Thus, the potential role of microplastics in influencing cellular metabolism and how this change in both the immune compartment and intestinal epithelium are impacting the gut microbiota will be discussed. This work was supported by NIEHS 1R56ES032037-01.

Tymofii Sokolskyi

Title

The Response of Nematode Gut Microbiomes to Aflatoxin B1

Abstract

As a functionally and taxonomically diverse community, the gut microbiome is on the frontlines against external stressors, ranging from pathogens to xenobiotics. In the present study, we analyzed community changes within the gut microbiome of a detritus-dwelling nematode Caenorhabditis elegans in response to a common toxin aflatoxin B1 and whether gut microbiome composition impacts host toxicity. Since the nematode gut is easily colonized by microbes from their external environment, we extracted a bacterial community from compost (which we call compost isolate, or CI), a native environment of C. elegans, and fed lab-grown, wild-type worms over multiple generations with various concentrations of aflatoxin B1. Wild nematodes harvested from the same habitat as CI were also subjected to the same experimental design. Over the course of the experiment, we regularly sampled worms to assess worm growth, levels of mitochondrial DNA damage, and community composition of the microbiomes using miSeq technology. Additionally, we exposed initial CI cultures and those from the C. elegans gut to aflatoxin B1 to observe their growth. Our research has shown that a diverse gut microbiome decreases aflatoxin-induced DNA damage in the host, with an increase in taxa capable of converting aflatoxin into non-toxic metabolites as a possible mechanism.

Isaiah Burciaga

Title

Cigarette Smoke, Fatty Diets, and the Microbiome

Abstract

Even though smoking rates have been falling through the years, some states are still lagging behind when it comes to quitting tobacco. About 25% of adult Kentuckians smoke cigarettes and about 18% of Kentuckian mothers admit to smoking while pregnant. Our research attempts to illuminate how cigarette smoke exposure (CSE) and the microbiome tie into the developmental origin of adult disease. In our lab, we intend on studying the effects of cigarette smoke exposure on the microbiome of mice. Additionally, we have introduced the secondary factor of a high fat diet. For our experiments, we are attempting to quantify the abundance of firmicutes and bacteroidetes within the feces of our mice. We are, in tandem with this, measuring the relative abundance of certain bacterial genes that are associated with carbohydrate processing, those being but and buk.

Kimberly Zorn

Title

Using Machine Learning to Predict Drug Effects on the Human Microbiome

Abstract

Exploration of the human microbiome has yielded knowledge of the increased complexity for drug discovery. Drugs that inhibit gut microbial growth can cause side-effects in patients, and drugs metabolized by gut bacteria can result in a depletion of drug availability. With the rising availability of data as well as computational power, in silico methods such as machine learning (ML) prediction has become a means to virtually screen compounds and focus testing. We describe herein a means to assist in pharmacological development by evaluating the effects of small molecules on gut microbiome-associated bacteria using multiple ML methods (deep learning, support vector classification, decision trees). As an example, we have utilized data from a recent publication to model the metabolism of 271 FDA-approved drugs by 76 bacteria (Zimmerman et al., Nature 570: 462, 2019). These models can be applied as a part of a pipeline to anticipate in vivo pharmacokinetic effects likely not observed during in vitro experiments. Furthermore, we can expand the applicability to any structure-activity relationship; for example, inhibition of bacterial growth, with many bacteria species present in public databases like ChEMBL and PubChem.

Pan Deng, Ph.D.

Title

Untargeted Stable-isotope Probing of the Gut Microbiota Metabolome Using 13c-labeled Dietary Fibers

Abstract

The gut microbiome generates numerous metabolites that exert local effects and enter the circulation to affect the functions of many organs. Despite extensive sequencing-based characterization of the gut microbiome, there remains a lack of understanding of microbial metabolism. Here, we developed an untargeted stable isotope-resolved metabolomics (SIRM) approach for the holistic study of gut microbial metabolites. Viable microbial cells were extracted from fresh mice feces and incubated anaerobically with 13C labeled dietary fibers including inulin or cellulose. High resolution mass spectrometry was used to monitor 13C enrichment in metabolites associated with glycolysis, the Krebs cycle, the pentose phosphate pathway, nucleotide synthesis, and pyruvate catabolism in both microbial cells and the culture medium. We observed differential use of inulin and cellulose as substrates for biosynthesis of essential and non-essential amino acids, neurotransmitters, vitamin B5, and other coenzymes. Specifically, use of inulin for these biosynthetic pathways was markedly more efficient than use of cellulose, reflecting distinct metabolic pathways of dietary fibers in the gut microbiome, which could be related with host effects. This technology facilitates deeper and holistic insights into the metabolic function of the gut microbiome.

Gen Li, Ph.D.

Title

It's All Relative: New Regression Paradigm for Microbiome Compositional Data

Abstract

Microbiome data are complex in nature, involving high dimensionality, compositionality, zero inflation, and taxonomic hierarchy. Compositional data reside in a simplex that does not admit the standard Euclidean geometry. Most existing compositional regression methods rely on transformations that are inadequate or even inappropriate in modeling data with excessive zeros and taxonomic structure. We develop a novel relative-shift regression framework that directly uses compositions as predictors. The new framework provides a paradigm shift for compositional regression and offers a superior biological interpretation. New equi-sparsity and taxonomy-guided regularization methods and an efficient smoothing proximal gradient algorithm are developed to facilitate feature aggregation and dimension reduction in regression. As a result, the framework can automatically identify clinically relevant microbes even if they are important at different taxonomic levels. A unified finite-sample prediction error bound is developed for the proposed regularized estimators. We demonstrate the efficacy of the proposed methods in extensive simulation studies. The application to a preterm infant study reveals novel insights into the association between the gut microbiome and neurodevelopment.

Shoshannah Eggers, Ph.D.

Title

Human Microbiome Mixture Analysis Using Weighted Quantile Sum Regression

Abstract

Studies of the health effects of the microbiome often measure overall associations by using diversity metrics, and individual taxa associations in separate analyses, and do not consider the correlated relationships between taxa in the microbiome. In this study, we applied random subset weighted quantile sum regression (WQSRS), a mixture method successfully applied to ‘omic data to account for relationships between many predictors, to processed amplicon sequencing data from the Human Microbiome Project. We simulated a binary variable associated with 20 operational taxonomic units (OTUs), 2 strong, 8 medium and 10 weak, which were chosen based on previously identified links to health outcomes. All other OTUs were assigned no association. WQSRS was used to test for the association between the microbiome and the simulated variable, adjusted for sex, and sensitivity and specificity were calculated. WQSRS predicted the correct directionality of association between the microbiome and the simulated variable, with a sensitivity and specificity of 75% and 60%, respectively, in identifying the 20 associated OTUs. The application of WQSRS to the microbiome allows for analysis of the mixture effect of all the taxa in the microbiome, while simultaneously identifying the most important to the mixture, and allowing for covariate adjustment.

Sridhar Mani, Ph.D.

Title

New Thoughts on the Evaluation of the Microbiome and Human Health: Impact of Microbial Movement

Abstract

We have recently uncovered a new phenomenon in the intestines of rodents and humans - bacteria are able to move en masse over rough intestinal surfaces (bacterial swarming) and only emerge when intestines are stressed (e.g., inflammation, polyps). Indeed, our assay picks up such movement from a fecal mixture and predicts a >85% specificity in detecting inflammation in humans. We have discovered a method to isolate these dominant swarming bacteria from feces and to our surprise when we administered these strains back to mice that already have intestinal inflammation, we see that swarming bacteria protect from inflammation. We made specific swarming deficient mutants of bacteria that lose protective effects in mice. We propose that bacterial swarm movement predicts for intestinal stress but in turn, is a host response to prevent pathological stress response. We conjecture that environmental toxicants, as well as dietary habits that affect health (gut health), could be assayed prior to ensuing pathologies. We conjecture that such technologies might have a role in monitoring the general health of a population as a point-of-care application. Our data is currently in peer review and preprints uploaded (bioRxiv 759886; doi: https://doi.org/10.1101/759886).

David Walsh, Ph.D.

Title

Tools and Methods for High-throughput Screening of Drugs Targeting Human Gut Microbiota

Abstract

The human gut microbiome offers a rich environment of disease biomarkers and therapeutic targets that could be leveraged to evaluate both environmental impact (e.g. insult) as well as potential countermeasures to mitigate downstream decrements to human health and performance. A significant challenge in evaluating changes of the gut in response to external stimuli is the lack of low-cost, high-throughput in vitro models available. Current in vitro methods are limited: 1) animal models are expensive and not always representative of human gut biology; 2) organ-on-a-chip systems and larger in vitro systems (i.e. SHIME) are more representative of human physiology; however, typically lack the high-throughput needed to generate large datasets; and, 4) standard anaerobic culture does not capture the complex microenvironment of the human gut lumen. MIT-Lincoln Laboratory's Artificial Gut ("ArtGut") system works to resolve these challenges by using a 3D-printed well plate design contained in a clamshell-like cover to allow for different culturing conditions on the top and bottom of fecal culture wells. Preliminary data for the ArtGut system shows donor stool samples were able to maintain their Shannon diversity over a 24-hour culture; while anaerobic culture was shown to cause significant shifts in diversity. We are currently working on developing methods for evaluating xenobiotics and potential countermeasures which could be readily translated to advanced animal models or human clinical trials.

Kelsey Thompson, Ph.D.

Title

Prioritization and Annotation of Novel Bioactive Small Molecules from the Microbiome

Abstract

Every human is constantly exposed to numerous chemical toxicants, many of which are ubiquitous in the environment at potentially-harmful concentrations. Gut-microbial biochemistry has recently been recognized as a major contributor to toxicant detoxification. Inter-individual variation in microbial carriage can result in either decreased or increased risk from toxicant derivatives, and it is thus crucial to better understand the underlying host-microbiome-chemical interactions. Here, we introduce an approach for identifying and prioritizing potentially bioactive metabolites from microbial communities, MACARRoN (Metabolome Analysis and Combined Annotation Ranks for pRediction of Novel bioactives). We initially applied this methodology to ~82k compounds spanning 546 metabolomes from 106 IBD patients and controls in the Integrative Human Microbiome Project (HMP2). Prioritization of potential bioactivity was done by integrating epidemiological properties (e.g. IBD pathogenesis) with ecological ones (e.g. covariation and prevalence). Top-ranked IBD associated features included novel metabolites, as well as bile acids and short-chain fatty acid precursors that have been previously implicated in IBD. These results indicate novel potentially immunomodulatory microbially-derived and -associated compounds in inflammatory conditions. We are currently expanding the classes of compounds assessed by the system to include parent and derivative toxicants excreted in stool samples, one of the primary routes for detoxification, to assess the levels and impact of daily exposures to environmental contaminants.

Sneha Couvillion, Ph.D.

Title

Discovering Novel Biomolecules in the Microbiome and the Organisms Who Make Them

Abstract

Humans are continually exposed to a large number of environmental agents that are foreign to the body, some of which are biotransformed by the gut microbiota and may have a beneficial or detrimental effect on health. Explaining the phenotypic influences on the host by microbial taxa—both known and unknown—and their specific functions still remain major challenges. In this talk we will present a novel approach of combining standards-free metabolomics and activity-based protein profiling strategies to address this gap in functional knowledge in microbiome research via the identification of novel biomolecules and the attribution of their production to specific microbial taxa. Comprehensive, untargeted characterization of the metabolome can help identify bioactive metabolites that modulate host phenotype. Activity-based probes can be tailor made for metabolite targets (or dietary compounds or drugs) that have been detected and identified using standards-free metabolomics and implicated to have an impact on the health of the host and the microbiome.

Michael McLaren, Ph.D.

Title

New Methods to Control for Experimental Bias in Microbiome Differential Abundance Analysis

Abstract

One of the most fundamental uses of sequencing-based microbiome measurement is to assay differential abundance (DA)—how particular microbes vary in their relative or absolute abundance with a host or environmental factor of interest. But such microbiome measurements are also known to be inaccurate due to protocol-specific experimental bias, and there has been little study of how bias affects the results of DA analyses. Here we argue that bias can lead to spurious DA results and describe several approaches that can be used to bound or correct these errors. We previously presented an approach using control communities; however, such communities must contain a representative taxonomic sample of the ecosystem under study and are currently unavailable for complex natural ecosystems. In this talk, we present new approaches that use cellular spike-ins or independent measurements (via qPCR or ddPCR) of one or a small number of taxa. These methods can provide calibrated DA estimates for all sequenced taxa, do not require control communities, and require only modest (or no) modifications to existing experimental designs. They therefore provide practical approaches to calibrated differential-abundance analysis in complex microbial ecosystems.

Emma Hall

Title

Relative Humidity in Air Controls VOC and MVOC Emissions off of Building Materials

Abstract

Humans on average spend 90% of their lifetimes indoors and are exposed daily to volatile organic compound (VOC) concentrations that are 1-2 orders of magnitude greater than ambient levels. A large portion of chemical emissions indoors are related back to building materials like carpet, drywalls and paints. House dust, a complex matrix of organic and inorganic materials, accumulate on these building materials and at elevated relative humidity (RH) can support microbial growth. Microbial VOCs are released during metabolic processes, leading to two possible sources of VOCs coming off a singular surface(s). However, the relationship between the relative humidity in air and VOCs and mVOCs emissions is not well understood. Emissions from carpet only and house dust embedded in carpet were determined by using a proton-transfer-reaction time of flight mass spectrometer (PTR-TOF-MS) which measured the emissions profile across an RH range of 50-95%. Unique profiles were observed at each RH, demonstrating the considerable effect of RH on material emissions themselves. At elevated RH the microbial contribution was evident by the release of compounds like dimethyl sulfide and a suite of monoterpenes for the carpet embedded with dust. Future work may elucidate efforts to detect microbial growth indoors utilizing mVOCs.

Noah Siegel

Title

Early Life Microbiome Perturbation Results in Persistent Composition and Functional Changes

Abstract

Rationale: The impact of environmental perturbations on infant gut microbiome development is not well understood. We hypothesized that early life gut microbiome dysbiosis might result in persistent and functional changes. To test this hypothesis, we treated newborn rhesus macaque monkeys with antibiotics and evaluated gut microbiome populations until 6 months of age. Methods: Monkeys were treated daily with ampicillin, gentamicin, and vancomycin during the first week of life. All animals were breastfed until weaned at 5 months of age. Microbial DNA was extracted from rectal swabs collected at birth and monthly. 16S rRNA sequencing was conducted on V3-V4 amplicons. Reads were analyzed to assess differences in diversity and metagenomic pathways. Results: The infant monkey gut microbiome consisted primarily of Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. While proportions of Actinobacteria, Bacteroidetes, and Proteobacteria declined with age, the opposite trend was observed with Firmicutes. At 6 months of age, α and β diversity increased in antibiotic-treated monkeys relative to controls, with more prominent effects in males relative to females. Metagenomic analysis revealed an overall reduction in pathways contributing to peptidoglycan biosynthesis in antibiotic-treated monkeys. Conclusions: Early life antibiotics resulted in gut microbiome alterations that persisted to 6 months of age. Differences in metagenomic pathways accompanied changes in microbial abundance and diversity. Microbiome changes were more pronounced in males relative to females. Our findings suggest that early-life environmental perturbations of the gut microbiome can have sex-dependent effects that persist during infancy.

Courtney Gardner, Ph.D.

Title

Exposures to Semivolatile Organic Compounds and Associations with the Gut Microbiome

Abstract

Semivolatile organic compounds (SVOCs) are widely detected in many indoor environments due to their frequent use in building materials, textiles, furniture, electronics, and other consumer products. Biomarkers of SVOC exposures have been consistently measured in biological samples across the globe, presenting uncertainty about their potential impacts on sensitive populations. To begin unravelling the dynamics between gut microbiome maturation and chronic exposure to complex chemical mixtures, this study characterized the prokaryotic and fungal gut microbiomes of children (ages 3–6) in a North Carolina cohort and examined their relationships with SVOC exposures. SVOC biomarkers were detected ubiquitously in pooled urine samples, with 29 compounds detected in >95% of samples. In total, 61 bacterial taxon–biomarker and 24 fungal taxon–biomarker pairs displayed statistically significant relationships (i.e., minimum positive rs ≥ 0.2 or minimum negative rs ≤ −0.2; p < 0.05), with disparate trends noted for bacteria and fungi. Sm-PFOS was associated with declines in several bacterial taxa (rs ≤ −0.21; p ≤ 0.05), while phthalate metabolites like MHiBP were negatively associated with fungi (rs ≤ −0.45). Finally, 10 genera historically capable of reductive dehalogenation displayed significant positive associations with halogenated SVOCs (e.g., biomarkes of chlorobenzenes such as 2,4-DCP), suggesting these compounds may act as a selective pressure within developing gut microbiomes.

Allison Zhang, Ph.D.

Title

Deep Sequencing Revealed Potential Microbial Exposure in Hospital Air

Abstract

In healthcare settings, it is crucial to maintain the environment sterility and effective disinfection methods to reduce infection rate during hospitalization. Increasing evidence suggests that the heating, ventilation and air conditioning systems (HVACs) contributes to the increased infectious risk in the hospital. Traditional method of using culturable microorganisms fails to characterize the complexity and diversity of the microbial community of indoor environment. We applied deep sequencing to ordinarily used HVAC filters acquired from different locations in a hospital. Both DNA and RNA were extracted from HVAC filters and subjected to shotgun sequencing, which provides better intraspecies diversity information and the addition of functional information compared with 16S sequencing. Using metagenomics and metatranscriptomics approaches, our results indicated that viridiplantae and bacteria are the most identified kingdoms/subkingdoms in DNA and RNA samples, respectively. Moreover, we found microbial exposures differ between rooms, possibly due to the difference in the type and amount of traffic. Interestingly, we identified species commonly associated with hospital acquired infections from HVAC samples, such as Streptococcus pneumoniae and Staphylococcus epidermidis, and common pathogens, such as Propionibacterium acnes. Our study demonstrated the diverse microbial community using shotgun sequencing and the presence of infection related microbes in hospital air.

Ian Buller, Ph.D.

Title

Geographic Variation in the Oral Microbiome of NIH-AARP Diet and Health Study Participants

Abstract

Geographic location of individuals may partially explain heterogeneity in the composition of their microbiota, but studies are limited. We evaluated the spatial variation of oral microbial communities in a subset of participants in the NIH-AARP Diet and Health Study, a cohort of men and women aged 50-71 years. Geocoded addresses were available and buccal cell specimens collected 2005-2006 were analyzed using 16S rRNA gene sequencing. We compared richness of observed species within and between six states (n=2,119) and 16 cites (n=1,817) in which participants resided. We evaluated differences using intraclass correlation coefficients (ICC), a measure of spatial clustering (Moran’s I), and non-spatial linear models (covariates: age, sex, and smoking status). Richness varied more within than between states (ICC=0.016; 95% CI:0.04-0.101), but no spatial autocorrelation was observed at the state level. Richness varied more within than between cities (ICC=0.015; 95% CI:0.004-0.046) with positive spatial autocorrelation observed within Sacramento (I=0.044; p=0.042; n=93) and negative within Philadelphia (I=-0.031; p=0.022; n=238). Model residuals were spatially autocorrelated in Philadelphia (p=0.025), suggesting variation was best explained by a spatial model. We demonstrated spatial variation in the oral microbiota of NIH-AARP participants within US cities but not states, suggesting the importance of spatial scale for future analyses.

Hannah Laue, Ph.D.

Title

The Microbiome as Mediator/Modifier in the Environmental Epidemiology of Autism

Abstract

In the New Hampshire Birth Cohort Study (NHBCS) we identified associations between 1) nutrient-toxic element mixtures and the early-life microbiome and 2) the microbiome and child behavior at three years. The extent to which the microbiome mediates/modifies the association between exposures and childhood behaviors is unknown. Six-week-old toenail clippings were analyzed for eleven elements (manganese, iron, nickel, copper, zinc, arsenic, selenium, cadmium, tin, mercury, and lead). Stool samples were collected from diapers at six weeks and one year of age, metagenomic sequencing was performed, and taxa/gene functions were inferred following established pipelines. At three years, parents completed the Social Responsiveness Scale, 2nd Edition (SRS-2), which assesses autism-related social behaviors. Both nutrient and toxic elements were associated with microbial taxa in six-week-old and one-year-old stools, but none of these taxa was also associated with social behaviors. Arsenic and tin were associated with decreased vitamin B6 biosynthesis genes (PWY0-845) in one-year-old stools, increased abundance of which was associated with better SRS-2 total T-scores. Formal mediation/modification analyses based on these preliminary findings is underway. Investigation of the potential mediating/modifying role of microbiome may help to elucidate the mechanisms by which environmental exposures influence autism-related social behaviors.

Thomas Sharpton, Ph.D.

Title

Zebrafish as a High-throughput Model for Disentangling Exposure-microbiome Interactions

Abstract

The vast diversity and variation of the exposome challenges the study of environmental health. To circumvent this challenge, researchers often turn to high-throughput model systems that enable rapid screens of the effect of specific exposures. The zebrafish has proven to be one of the most powerful such models in that it affords access to large sample sizes, automated exposure and phenotyping platforms, and short generation times. In recent years, zebrafish have also emerged as a useful system for studying host-microbe interactions as well as how the microbiome mediates the effect of exposure on physiology. In this presentation, I summarize the utility and potential for the zebrafish to accelerate our understanding of how exposures interact with the microbiome to impact health. I introduce key analytical and experimental tools we innovated to this end, including gut metagenomic gene catalogs, longitudinal sampling designs, and high-throughput germ-free fish assays. Finally, I offer an overview of how we use zebrafish to study the effect of PAH exposure on gut microbiome assembly and the impact of these effects on neurodevelopment.

Selma Podbicanin

Title

Gestational CSE Alters Dam and Offspring Intestinal Bacterial Microbiomes

Abstract

Maternal smoking while pregnant results in negative offspring health outcomes including low birth weight and an increased risk of obesity. In Kentucky, ~18% of women smoke during pregnancy. In this study, we have exposed C57BL/6 dams throughout gestation to cigarette smoke generated from Marlboro ™ Red commercial cigarettes which yields a low birth weight phenotype. We examined the fecal/cecal bacterial microbiome profiles of the dams at the initiation of exposure and prior to parturition as well as in offspring throughout development (1.5, 3 and 7 weeks of age). We found clear and compelling evidence of alterations in maternal and offspring intestinal bacterial community membership at each of the time points studied. Correlation of outcomes with indices of offspring health are ongoing.

Ya Wang

Title

Characterizing Microbial Community Viability with High-throughput Sequencing in Built Environments

Abstract

Characterizing microbial viability is significant: essentially all sequence-based technologies do not differentiate living from dead microbes, whereas the phenotypes of microbiomes are defined by the viable organisms. This is particularly critical in built environments, where dead microbes are often in greater prevalence and abundance than viable ones. Our understanding of microbiome structures and their transmission between humans and our surroundings thus remains incomplete. As a potential solution, several sequencing-based technologies have been proposed to quantify the viable fraction of a microbial community, but their reliability have not been evaluated. Our work benchmarked high-throughput sequencing variants based on chemical-treatment (propidium monoazide treatment followed by 16S rRNA amplicon-sequencing, PMA-seq) and RNA(cDNA)-amplification (parallel amplicon-sequencing on 16S rRNA transcripts and genes, 16S-RNA-seq) for viability assessment in synthetic and realistic microbial communities. In synthetic communities, both techniques successfully reconstructed the mixtures of live/heat-killed E.coli and S.sanguinis. However, viability was not accurately assessed in natural microbiomes from human and indoor environments. The performance of PMA-seq was largely affected by sample source, microbial diversity and biochemical backgrounds, while 16S-RNA-seq failed to differentiate RNA(viable) vs. DNA(whole) communities compositionally. This would suggest that neither technologies reflect true viability in complex communities. Results were slightly different in samples of similar origins (from Boston subway systems). Several taxa were enriched/depleted significantly after PMA-treatment; samples were differentiated by source as well as by library type via 16S-RNA-seq. These indicated that sequencing-based viability assessments work more reliably under similar biological and biochemical backgrounds. Overall, our results show that PMA-seq and 16S-RNA-seq do not reflect microbial viability outside of very simple, synthetic communities. Our next step is to develop new assays based on protein-coding genes, as well as to improve the assessment with multi-omic integration.

Maude David, Ph.D., Oregon State University

Title

Impact of the Interplay Between Microbiota and Environment on Neurological Disorders

Abstract

Many studies have associated environmental exposure to chemicals with neurological impairments, including neurodevelopmental disorders. Autism Spectrum Disorder, for example, has been associated with prenatal exposure to air pollution or pesticides, and behavioral development can be affected postnatally by exposure to persistent compounds such as organochlorides. For ingested compounds especially, the gastro-intestinal tract is the first physical and biological barrier to foodborne chemicals and organic pollutant, and recent research suggests that the gut microbiota could play a major role in the toxicity of these compounds. The David lab studies the association of the gut microbiota with Autism Spectrum Disorder and conducted a large longitudinal crowdsourced study of young siblings (2-8 years old, +/- 2 years from each other). With this design, we minimized the environmental exposure differences within families, and pinpointed microbial taxa specific to our autism cohort. Additionally, we documented over 100 lifestyle, environmental, and diet variables, which were also closely associated with the majority of the biomarkers and microbial community. Furthermore, the microbial structure correlated with the reported severity of the autism phenotype, and changes in the microbial community over time were significantly linked to longitudinal anxiety scores. These observations suggest complex microbiome - autism-environmental interactions, which will be discussed in this presentation.