September 22-23, 2021
Virtual Event

John Cryan, Ph.D.

Title

Gut Feelings: Microbiome as a Key Regulator of Brain and Behavior Across the Lifespan

Abstract

The microbiota-gut-brain axis is emerging as a research area of increasing interest for those investigating the biological and physiological basis of neurodevelopmental, age-related and neurodegenerative disorders. The routes of communication between the gut and brain include the vagus nerve, the immune system, tryptophan metabolism, via the enteric nervous system or via microbial metabolites such as short chain fatty acids. These mechanisms also impinge on neuroendocrine function at multiple levels. Studies in animal models have been key in delineating that neurodevelopment and the programming of an appropriate stress response is dependent on the microbiota. Developmentally, a variety of factors can impact the microbiota in early life including mode of birth delivery, antibiotic exposure, mode of nutritional provision, infection, stress as well as host genetics. Stress can significantly impact the microbiota-gut-brain axis at all stages across the lifespan. Recently, the gut microbiota has been implicated in a variety of conditions including obesity, autism, schizophrenia and Parkinson's disease. Moreover, animal models have been key in linking the regulation of fundamental brain processes ranging from adult hippocampal neurogenesis to myelination to microglia activation by the microbiome. Finally, studies examining the translation of these effects from animals to humans are currently ongoing. Further studies will focus on understanding the mechanisms underlying such brain effects and developing nutritional and microbial-based intervention strategies.

Brief Biography

John F. Cryan is Professor and Chair, Dept. of Anatomy and Neuroscience, University College Cork, Ireland and is also a Principal Investigator at APC Microbiome Ireland Cryan's current research is focused on understanding the interaction between brain, gut and microbiome and how it applies to stress, psychiatric and immune-related disorders at key time-windows across the lifespan. Cryan has published over 550 articles and is co-author of the bestselling “The Psychobiotic Revolution: Mood, Food, and the New Science of the Gut-Brain Connection” from National Geographic Press. He has received numerous awards including UCC Researcher of the Year in 2012; UCC Research Communicator of the Year 2017, the University of Utrecht Award for Excellence in Pharmaceutical Research in 2013 and being named on the Thomson Reuters/Clarivate Highly Cited Researcher list in 2014, 2017 and 2018. He was elected a Member of the Royal Irish Academy in 2017. He also received a Research Mentor Award from the American Gastroenterology Association and the Tom Connor Distinguished Scientist Award from Neuroscience Ireland in 2017 and was awarded an honorary degree from the University of Antwerp, Belgium this Spring. He was a TEDMED speaker in 2014 and is a Past-President of the European Behavioral Pharmacology Society.

Rima Kaddurah-Daouk, Ph.D.

Title

The Gut Brain Chemical Axis: Gut Microbiome, Genome, and Metabolome Influences

Abstract

The gut microbiome plays many critical roles in human health and disease. The trillions of microbes that inhabit everyone's bodies contribute to metabolic and immunological states. Humans and bacteria cooperate to process a wide range of chemicals from food, xenobiotics, environmental exposures, and metabolites produced by cells. Bidirectional biochemical communication between the gut and brain has been demonstrated mechanistically in animal models and suggested by association studies in humans, contributing to neurodegenerative and psychiatric diseases such as depression, schizophrenia, autism, multiple sclerosis, Parkinson's, and recently Alzheimer's disease (AD). Yet the details, and, especially, causation in humans, remain poorly defined. The Alzheimer Gut Microbiome Project (AGMP) funded by NIA and in partnership with the American Gut Project, The AD Metabolomics Consortium, Eight Alzheimer Research Centers (ADRCs), the National Centralized Repository for AD and Related Dementias (NCRAD), The National Alzheimer's Coordinating Center (NACC), Large diet and lifestyle studies (MIND, U.S. Pointer and BEAT-AD), Centers of excellence in informatics and systems biology and Preclinical model systems, are jointly defining the biochemical axis of communication between the gut microbiome and the brain. Kaddurah-Daouk's team is defining links between gut metabolites and AD phenotypes and brain imaging changes. Kaddurah-Daouk will highlight key findings that illustrate the connections between genome gut microbiome metabolome and pathological changes in AD and in related neuropsychiatric disorders. Kaddurah-Daouk will share findings related to anxiety, depression and sleep disruption.

Brief Biography

Kaddurah-Daouk, Ph.D., is a professor in the departments of Psychiatry and Medicine at Duke University Medical Center. She is a graduate of the American University of Beirut Department of Biochemistry with subsequent training at Johns Hopkins (worked with Nobel Laureate Hamilton Smith), Massachusetts General Hospital and the Massachusetts Institute of Technology. She has been a seminal force in the development of applications for metabolomics in the medical field.

She co-founded the Metabolomics Society and served more than four years as its founding president, helping create a presence and voice for an interactive metabolomics community (currently close to 1000 members). She co-founded Metabolon, a leading biotechnology company for applications in metabolomics, and two other biotechnology companies. With significant NIH funding (over 40 grants funded), she established and leads large consortia (more than 120 scientists from over 30 academic institutions). The Alzheimer's Disease Metabolomics Consortium (ADMC), funded by the National Institute on Aging (NIA) and in partnership with the Alzheimer's Disease Neuroimaging Initiative, is one of six consortia under the Accelerating Medicine Partnership for Treatment of Alzheimer's Disease (AMPAD) and Molecular Mechanisms of the Vascular Etiology of Alzheimer's Disease (M²OVE-AD) initiatives set to respond to President Obama's challenge: “National Plan to Address Alzheimer's Disease” to treat or prevent Alzheimer's disease (AD) by 2025.

The consortium is mapping metabolic failures across the trajectory of AD connecting peripheral and central changes, defining genetic basis for metabolic alterations and molecular basis for resilience during aging. The NIMH-funded Mood Disorder Precision Medicine Consortium (MDPMC) seeks to optimize treatment outcomes in depression (in partnership with the Mayo Clinic, Emory, and several other institutions). Recently she established the Alzheimer Gut Microbiome Project (AGMP), an initiative that includes leadership from the gut microbiome, AD, depression and metabolomics fields with a mission to define a possible role for gut microbiome in AD and other neuropsychiatric diseases and for defining gut brain chemical axis of communication and alterations during aging. The NIA committed over $27 million to fund this project, which includes Duke, UCSD, Rush, Caltech, and many other academic institutions (Alzheimer's Gut Microbiome Project - Rima Kaddurah-Daouk).

Earlier work funded by the National Institute of General Medical Sciences (NIGMS) through the Pharmacometabolomics Research Network established foundations for a new field “Pharmacometabolomics”, which parallels and informs pharmacogenomics and in which metabolic profiles of individuals are used to inform about treatment outcomes. This consortium established foundations for use of metabolomics data as a compliment for genomics data in precision medicine approaches. Kaddurah-Daouk leads several initiatives and task groups in Precision Medicine where the metabolome captures net influences of genome, gut microbiome, exposome and diet influences and where big data can inform about health of each individual in real time. She has partnerships that spans USA Europe Canada and Australia and that includes a partnership with Oxford Nightingale and UK Biobank for evaluating metabolic profiles of 125,000 subjects enrolled in UK Biobank. She has over 150 peer reviewed scientific publications, leads in a large number of active NIH grants (including 3 RO1s, U19, U01, 6 others) and has more than 60 patents or patent applications.

Juliette Madan, M.D., M.Sc.

Title

The Developing Microbiome in the Critical Window of Neurodevelopment: The Gut Brain Axis and Relationship with Social and Emotional Development

Abstract

The human intestinal microbiome begins its development in earnest at the time of birth, as microbes are rapidly acquired during delivery and through feeding and the environment. As the microbiome is established, the innate and adaptive immune system are developing in parallel, requiring interaction with the gut microbes in order to mature. The gut microbiome and its interrelationship with the brain begins in utero, impacted by intrauterine and extrauterine factors including maternal antibiotics, stress, toxicant exposures, diet, delivery mode, and feeding during infancy. The factors that influence the gut microbiome development are thought to impact signaling along the microbiome-gut-brain axis, which has been implicated in a variety of neuropsychiatric and neurodevelopmental outcomes including autism, inattention, anxiety and cognition.

Work from the Children's Environmental Health and Disease Prevention Research Center at Dartmouth and the NIH ECHO program encompasses the New Hampshire Birth Cohort Study, and is focused on environmental epidemiology during pregnancy and neonatal life through childhood. This research includes neurodevelopmental outcomes in the context of environmental exposures and microbiome development. Many studies of the microbiome in ASD are complicated by cross sectional designs with measures taken at the time of diagnosis. The cohort is designed to capture prospective longitudinal molecular markers in the critical window of pregnancy and early life during which time the microbiome is developing and interacting with the immune system and the brain, providing opportunities for intervention. Madan and her team have studied microbiome samples longitudinally and measuring the SRS-2 (measures of social development associated with ASD) at 3 years of life, identifying patterns that precede ASD diagnosis at preschool age.

In addition, the lab examined the relationships between the infant microbiome at multiple early-life timepoints and continuous measures of internalizing and externalizing behaviors as measured using the BASC-2 (the behavioral assessment scale for children which captures adaptive and maladaptive behaviors at ages 2-5 years) stratified by sex, finding associations with inattention, anxiety and depression in early life. Evaluation of exposures, the microbiome, and neurodevelopmental health provides important opportunities to intervene to optimize health outcomes for a lifetime.

Brief Biography

Juliette Madan, M.D, M.Sc., is board certified in neonatology-perinatology and an Associate Professor of Pediatrics, Epidemiology and Biomedical Data Sciences at Geisel School of Medicine at Dartmouth. Madan is the Clinical Director of the Dartmouth Children's Environmental Health and Disease Prevention Research Center and the New Hampshire Birth Cohort Study, and the focus of her research is on the developing microbiome in infants and children and the relationship to immune training and health outcomes that are alterable. She is the founding director of the Psychiatry Immunology and Neurology Group at Dartmouth, which aims to provide clinical care and translational research initiatives in infection and inflammation mediated neuropsychiatric illnesses in children and young adults. Madan's lab is focused on the relationship between the gut microbiome and neurodevelopmental outcomes such as autism, anxiety and cognition, as well as immune mediated neuropsychiatric outcomes and translation to interventions such as nutritional, probiotic regimens and fecal transplant.

Anita Kozyrskyj, Ph.D.

Title

Critical Periods in the Establishment of Gut Microbiota During Infancy for Neurodevelopment

Abstract

Hein M. Tun, Sukhpreet Tamana, Carmen Tessier, Piushkumar J. Mandhane, Jacqueline Pei, James A. Scott, Anita L. Kozyrskyj.

Dysbiosis of gut microbiota has been linked to neurodevelopmental phenotypes such as autism spectrum and attention-deficit disorders. Gut microbiota pathways to neurodevelopment in healthy infants are largely unknown. Commencing with an overview of infant gut microbial development, in this presentation Kozyrskyj will provide evidence for critical periods for gut microbiota and metabolite-specific pathways to neurodevelopment. The evidence will be derived from the gut microbiome at 2 critical periods during infancy and neurodevelopment in a general population of 400 infants from the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study. Neurodevelopmental outcomes will be represented by the Bayley Scale of Infant Development (BSID-III) at one and two years of age. Microbiota and metabolite profiling will be based on 16S rRNA gene sequencing, qPCR and NMR analysis of infant fecal samples at a mean age of four and twelve months.

Late infancy study (Gut Microbes 2021): Among 3 gut microbiota enterotypes identified in term infants at 12 months, higher scores for cognitive, language and motor development were seen 12 months later at age two with the Bacteroidetes-dominant cluster (32% of infants) relative to the Proteobacteria-dominant cluster (22% of infants) in covariate-adjusted GLM models. When stratified by sex, only male infants with a Bacteroidetes-dominant microbiota exhibited more favourable cognitive (5.9 points) and language (7.9 points) development. Similar associations were evident for change in BSID-III scores between ages one and two. The relative abundance of genus Bacteroides in gut microbiota was positively correlated with cognitive and language scores at age two. Enhanced sphingolipid synthesis and metabolism, and antagonism between Bacteroides and Streptococcus were characteristic of the Bacteroidetes-dominant enterotype.

Early infancy study (unpublished): No associations were evident between four-month microbiota clusters and BSID-II scores at age two. However, cognitive and language scores were lower in infants colonized by C. difficile (detected by qPCR) at four months of age. This microbiota symbiont in infants influences fecal levels of many microbial metabolites. Further, C. difficile relative abundance (gene copies per total bacterial gene copies) or gut microbiota metabolite concentrations, in conjunction with exclusive breastfeeding duration, were found to mediate inverse associations between maternal prenatal depression, and cognitive or language scores in a sex-dependent manner.

This research found strong temporal and ‘dose-response' evidence of a positive association between Bacteroides gut microbiota of late infancy and neurodevelopment in male infants. The late infancy Bacteroides findings have been reproduced in human infants by the RC Knickmeyer lab. Results on early infancy will soon be published and remain to be reproduced.

Brief Biography

Anita Kozyrskyj, Ph.D., is Professor of Pediatrics at the University of Alberta, Canada. She leads the SyMBIOTA (Synergy in Microbiota) research program on early-life environmental shaping of the infant gut microbiome, and child immune-related and neurodevelopmental outcomes in the CHILD Cohort Study. SyMBIOTA was funded by the 2010 CIHR Microbiome Initiative and is now part of CIHR's IMPACTT microbiome research network, where Kozyrskyj is co-PI of the Human Cohort Design and Analyses Platform. Kozyrskyj's SyMBIOTA program has generated 40 papers, 2 book chapters and trained many next generation microbiome researchers. Her microbiome papers have received awards for being the most influential, and have been cited by position statements on food allergy and neonatal early-onset bacterial sepsis. She is associate editor of J Dev Orig Health Dis, a DOHaD Canada Council member and one of the directors of the inVIVO Planetary Health Network.

Nafissa Ismail, Ph.D.

Title

Puberty, a Vulnerable Period for Stress-induced Changes in the Gut Microbiome: A Possible Opportunity for Probiotics

Abstract

Puberty is a critical period of development characterized by rapid physiological changes and significant brain reorganizing and remodeling. These rapid changes render the developing brain particularly vulnerable to stress and immune challenge. Epidemiological studies show that stress-related mental illnesses often onset during puberty with a higher prevalence rate in females than in males at about a 2:1 ratio (Angold and Costello, 2006). In mice, exposure to an immune challenge (lipopolysaccharide; LPS) during puberty causes enduring effects on stress reactivity, and depression-like behavior in females and anxiety-like behavior in males later in life. The gut microbiome regulates stress and inflammatory responses and can alter brain chemistry and behavior through the gut-brain axis. Thus, the gut microbiome appears to mediate stress-induced sex-specific changes in behavior.

Recent work from Ismail’s laboratory shows that pubertal stress exposure changes the gut microbiota in a sex-dependent manner. However, Ismail’s work also shows that pubertal probiotic treatment changes the acute immune response in a sex-specific manner and mitigates the effect of pubertal immune challenge on the neural mechanisms involved in stress and immune responses, such as glucocorticoid and serotonin receptor expressions. Pubertal probiotic treatment also blocks stress-induced depression-like in females and anxiety-like behaviors in males. These findings show that the gut-brain axis plays an important role in the development of mental illness during puberty and that manipulation of the gut-brain axis with probiotics can lead to a resilience to stress-induced mental illnesses in males and females.

Brief Biography

Nafissa Ismail, Ph.D., is an Associate Professor at the School of Psychology at the University of Ottawa and the holder of a University Research Chair in Stress and Mental Health. She obtained her Ph.D. from Concordia University in 2009. She then completed a post-doctoral fellowship at the University of Massachusetts and joined the University of Ottawa in 2012. Her research expertise is in Neuroimmunology and Neuroendocrinology. She was awarded Young Researcher of Year by the University of Ottawa and Early Researcher Award by the province of Ontario. She was also awarded the prize for activity in the media and in the community in 2021 by the Faculty of Social Sciences. She is also a member of the Global Young Academy.

Ali Keshavarzian, M.D., F.R.C.P., F.A.C.P., A.G.A.F., M.A.C.G.

Title

The Microbiome as a Mediator of Environmental-induced Susceptibility to Parkinson’s Disease: Evidence and Mechanisms

Abstract

Robin M Voigt, Christopher B Forsyth, Stefan J Green, Phillip A Engen, Ankur Naqib, Deborah A Hall, Christopher Goetz, Ali Keshavarzian.

Parkinson’s disease (PD) is an unrelenting, progressive neurodegenerative disease that affects 1-2% of the population over 60 years of age, with incidence rising in recent years. While it is true that the number of people living to advanced age is higher than in previous decades, the recent increase in incidence cannot simply be explained by an aging population and strongly suggests a central role for environment factor(s) in PD pathogenesis. Environmental factors like diet, exercise, sleep/circadian rhythms, and pollution/pesticides are well established to influence risk of neurodegeneration. Interestingly, many of these factors also impact the micro-organisms that live on and inside the body called the microbiome.

There is emerging evidence that microbiome can contribute to the pathogenesis of neurological disorders such as Alzheimer’s disease, multiple sclerosis, and PD. Therefore, environmental factors may promote PD through a mechanism including changing the microbiome. PD is characterized by loss of dopaminergic neurons and alpha-synuclein (α-syn) aggregates in the brain, but the exact causes of sporadic PD remain elusive, but inflammation is thought to be critical. One cell type in the brain that is thought to be the primary source of inflammation are microglia, which are the resident immune cells in the brain. When chronically activated, microglia produce pro-inflammatory cytokines that can cause aggregation of α-syn and damage neurons. However, the trigger and underlying mechanism(s) for microglia activation remains to be elucidated. Keshavarzian’s group and others have demonstrated that patients with PD have abnormal intestine and naso-oral microbiome (community structure and function).

The microbiome is a plausible trigger/enabler for microglia activation and neuroinflammation in PD because: (1) the microbiome is profoundly impacted by environmental factors, (2) changes in the microbiome can influence systemic-and neuro-inflammation through multiple mechanisms including changing the intestinal barrier, pro-inflammatory bacterial components, and bacterial metabolites, and (3) the PD-associated stool microbiome is sufficient to promote accelerated PD-like outcomes in a genetically susceptible mouse model. Environmental factors robustly influence the microbiome and may contribute to PD development and/or progression; therefor, future studies are compelled to identify how environmental factors that influence susceptibility to PD influence the microbiome. There is an urgent unmet need to develop disease-modifying interventions and microbiota-directed interventions should be considered. In this presentation, Keshavarzian will provide an overview of environmental factors that could promote dysbiosis in PD including diet (including bacteria/toxins contaminated food), pesticides, air/light pollution, and neighborhood.

Brief Biography

Ali Keshavarzian, M.D., F.R.C.P., F.A.C.P., A.G.A.F., M.A.C.G., is the Josephine M. Dyrenforth Chair of Gastroenterology, Professor of Medicine, Physiology and the Graduate College, Associate Dean-Faculty Mentoring and Director-Rush Center for Integrated Microbiome and Chronobiology Research at Rush University Medical Center, Chicago, IL. He joined RUMC in July 1999 and was Director of the Division of Digestive Diseases until Feb. of 2021. He is a practicing gastroenterologist with a specialty in managing patients with inflammatory bowel disease for 35+ years. His research includes basic science, translational, and clinical research focused on the impact of environmental factors (diet, stress, alcohol, sleep/circadian disruption) on the gut microenvironments (microbiota and barrier function) as well as the impact of gut-derived inflammation on gastrointestinal and systemic disorders including metabolic syndrome and neurodegenerative diseases. His innovation and dedication to research has been continuously supported by the NIH since 1986 resulting in 370+ publications and a h-index of 90.

Haydeh Payami, Ph.D.

Title

In Search of Triggers and Modifiers of Parkinson’s Disease in the Gut

Abstract

The composition of gut microbiome is altered in Parkinson's disease (PD). Characterization of this dysbiosis in humans is the critical first step to generate leads to inform mechanistic studies for understanding the role of gut microbiome in disease pathogenesis. A comprehensive metagenomics profile of PD gut microbiome obtained using deep shotgun sequencing of fecal samples from 492 PD and 242 age and geographically matched neurologically healthy subjects revealed as much 12% of all detected species and 30% of the most common microbial genes have significantly altered abundance in PD, depicting a far more complex and widespread dysbiosis than previously suspected based on 16S data. Network analysis showed PD-associated species form multiple clusters of interconnected communities that are enriched together or depleted together. The labyrinth of dysbiotic networks might seem daunting but can be disentangled. Some clarity will come from identifying the changes that are caused by disease and PD drugs, and the changes that precede the diagnosis of PD by examining the metagenome in individuals who have REM sleep behavior disorder most of whom will develop PD or related synucleopathies. Further clarity will emerge as the dysbiotic microbial clusters are linked to PD-associated genes and environmental factors. With this information, mechanistic and translational research can be appropriately targeted on key organisms and microbial clusters to establish cause and effect, and to improve treatments.

Brief Biography

Haydeh Payami, Ph.D., received her Ph.D. in Genetics from the University of California at Berkeley. She has served as Professor of Genetics and Neurology at Oregon Health & Science University, Senior Research Scientist and Director of Genomics Institute at New York State Department of Health Wadsworth Center, and is currently Professor and Endowed Chair in Parkinson’s research in the Departments of Neurology and Genetics at the University of Alabama at Birmingham. Payami is the founder and the lead investigator of the NeuroGenetics Research Consortium. Payami lab studies the interaction of the human genome, the gut microbiome and environmental factors in the etiology, progression and treatment of neurodegenerative disorders.

Timothy Sampson, Ph.D.

Title

Microbiome Contributions to Experimental Models of Amyloid Disease

Abstract

Indigenous microorganisms colonizing the human body are not simply spectators to host activity, but instead actively modulate critical aspects of physiology. At the physical and physiological interface between the host and environment, the community of microbes within the gut is poised to facilitate these interactions. Growing evidence demonstrates microbial influence on neurological function in both health and disease, and altered microbiome communities appear in various neurological conditions, including Parkinson's and Alzheimer's diseases. Experimental data from us and others, using gnotobiotic mouse models, suggest that these associations have meaningful impacts on amyloid pathologies and neuroinflammation. In addition, particular bacterial taxa and specific gene products have been identified that are capable of modulating neuropathologies from the gut. Outstanding questions remain, including identifying precise mechanisms of microbiome-brain communication and how pathological microbes or their products become enriched within a disease-associated microbiome (for instance, in response to environmental exposures). Gnotobiotic models, informed by the increasing power of human observations, will provide a framework to parse out these complex interactions and determine microbiome contributions to many neurological diseases.

Brief Biography

Tim Sampson, Ph.D., obtained his B.S. in Microbiology from the University of Pittsburgh and his Ph.D., in Microbiology and Molecular Genetics from Emory University prior to post-doctoral training at the California Institute of Technology. He joined the faculty in the Department of Physiology at Emory University in 2019 and the Dept. of Cell Biology in 2021. His lab is broadly interested in the potential roles of the gut microbiome in modulating neurological function, particularly neurodegenerative diseases. Given the rise of association studies indicating altered gut microbiomes during various disease states, they seek to understand the functional consequences of this dysbiosis. The lab is particularly interested in understanding how disease-associated environmental toxicants can alter the microbiome, its metabolic output, to synergize towards neurodegenerative outcomes. Utilizing gnotobiotic models, in conjunction with a reductionist host-pathogen approach, they dissect contributions of individual microbes and their metabolites in order to identify contributing or protective factors to neurological outcomes.

Rebecca Knickmeyer, Ph.D.

Title

Neuroimaging Provides New Insights Into the Infant Microbiome-gut-brain-axis

Abstract

During infancy and early childhood, rapid and profound changes in the intestinal microbiota are accompanied by dramatic changes in brain structure and functional organization. Neuroimaging techniques including structural MRI, diffusion tensor imaging (DTI), and resting state fMRI can be used in concert with studies of the gut microbiome and microbial metabolites to better understand the development of the microbiome-gut-brain axis during this critical period. In this presentation, Knickmeyer will review several major imaging modalities and what they have revealed about brain development in infancy and early childhood. She will also present several studies, conducted by her research team, which integrated neuroimaging data and 16s rRNA sequencing data to reveal (1) associations between alpha diversity and functional connectivity of the infant brain and (2) features of the infant gut microbiome are associated with amygdala and medial prefrontal cortex volumes.

Brief Biography

Rebecca Knickmeyer, Ph.D., has 20+ years' experience working at the cutting-edge of cognitive developmental neuroscience. She received her Ph.D. in Experimental Psychology from the University of Cambridge (U.K.) in 2005 and completed her postdoctoral training in the Neurodevelopmental Disorders Research Center at the University of North Carolina at Chapel Hill. She is currently an Associate Professor in the Department of Pediatrics and Human Development at Michigan State University, a member of MSU's Institute for Quantitative Health Sciences and Engineering, and co-director of MSU's Center for Research in Autism, Intellectual, and Other Neurodevelopmental Disabilities. The goal of Knickmeyer's lab is to identify genes and molecular pathways associated with altered brain development in infancy and early childhood through the integration of pediatric neuroimaging with cutting-edge techniques in genomics, metagenomics, and analytical chemistry. She has a particular interest in mechanisms underlying sexual differentiation of the brain and the microbiome-gut-brain axis. She is the author of over 80 scientific publications including manuscripts in high impact journals such as Science, Nature Communications, PLOS Biology, and Biological Psychiatry. She is director of ORIGINs (the Organization for Imaging Genomics in Infancy), a working group of the ENIGMA Consortium (Enhancing NeuroImaging Genetics through Meta-Analysis), serves on the editorial board of Molecular Autism, and belongs to numerous professional organizations including the Society for Neuroscience and the American College of Neuropsychopharmacology.

Maria Gloria Dominguez-Bello, Ph.D.

Title

Early Impacts on the Early Microbiome, and Brain: Early Findings

Abstract

The human microbiome is human-adapted, and transmitted through generations, with the primordial exposure to maternal microbes occurring during birth. In societies, many early stressors impair early microbiont's transmission and colonization, and early microbiome perturbations have been associated with increase in immune and metabolic diseases that are rocketing in industrialized countries. C-section birth deprives the nascent baby from the natural exposure to maternal microbes of the birth canal. There is some epidemiological evidence indicating an increased risk of ADS in C-section born babies, and since germ-free mice show an abnormal brain structure, Dominguez-Bello's team hypothesized that C-section birth also affects the brain. She and her team measured proteins of brain proliferation in mice born by C-section or not at P7 and P14. Preliminary results indicate increased neuroproliferation in the cerebellum and hippocampus (not in the medial prefrontal cortex) in mice born by C-section. Since C-section is compounded factors (lack of labor, early birth, surgery, lack of vaginal microbial exposure, and in mice, fostering), the microbial contribution to this effect remains to be determined.

Brief Biography

Maria Gloria Dominguez-Bello received her Ph.D. from University of Aberdeen, Scotland, and is currently the Henry Rutgers Professor of Microbiome and Health at Rutgers University, and the Director of the New Jersey Institute for Food Nutrition and Health. She is a fellow at the American Academy of microbiology, and at IDSA, and belongs to the editorial board of several scientific journals. She is leading the global initiative of the Microbiota Vault, to preserve the diversity of the microbes relevant to human health. Through global synergistic collaborations her lab uses multidisciplinary approaches to study impacts of modern practices on the microbiome and strategies for restoration.

Hannah Holscher, Ph.D.

Title

Dietary and Microbial Connections to Mood and Cognition

Abstract

The importance of diet in host-microbe interactions is increasingly recognized. The nutrient composition of meals affects the composition and functions of the gastrointestinal microbiota. Beneficial effects of diet on the microbiota include the provision of dietary fibers that intestinal microorganisms ferment to produce short-chain fatty acids. Alternatively, the Western diet, which is low in fiber and high in saturated fat and sugar, affects the intestinal microbiota composition and contributes to gut and systemic inflammation. As microbial metabolites and inflammation are involved in gut-brain communication, the interrelationship of diet, microbiota, and brain health is an area of increasing interest. Indeed, there is accumulating evidence that dietary impacts on the human intestinal microbiota are linked to brain health—consumption of high-quality diets, prebiotics (selectively metabolized substrates), and probiotics (live microorganisms) have been shown to affect mood and cognition. While promising, more research is needed to better understand the role diet plays in communication along the gut-microbiota-brain axis and how dietary approaches can be utilized to improve brain health.

Brief Biography

Hannah Holscher, Ph.D., is an Associate Professor of Nutrition in the Department of Food Science and Human Nutrition and a member of the Division of Nutritional Sciences, the Institute of Genomic Biology, and the National Center for Supercomputing Applications at the University of Illinois, where she joined thefacultyin2015. She completed postdoctoral training focused on the human microbiome, a Ph.D. in Nutritional Sciences, and a B.S. in Food Science and Human Nutrition at the University of Illinois. She is also a Registered Dietitian. Holscher’s laboratory uses clinical interventions and computational approaches to study the interactions of nutrition, the gastrointestinal microbiome, and health. Her creative use of machine learning approaches to determine microbial biomarkers of food intake and human health status resulted in her recognition as a 2017 New Innovator in Food and Agricultural Research and a 2020 National Academy of Medicine Emerging Leader. She also received the 2021 American Society for Nutrition’s Mead Johnson Young Investigator Award for her series of work on nutrition and the human microbiome. She has received grant funding from the United States Department of Agriculture (USDA), the Foundation for Food and Agriculture Research, food commodity boards, and private industry. She has published 54peer-reviewed manuscripts and given59invited presentations at locations including the National Academy of Medicine, National Institutes of Health, USDA, universities, and national society meetings of nutrition scientists, food scientists, and dietitians. She has served in local and national leadership roles, including Chair of the Nutrition Translation (2017-2020) and Nutritional Microbiological (2020-2023) Research Interest Sections of the American Society for Nutrition. Holscher currently serves on The Journal of Nutrition editorial board and as an associate editor for Nutrition Research and Gut Microbiome.

Lawrence David, Ph.D.

Title

Individual Variation in Diet Response

Abstract

Dietary carbohydrates that are metabolized by gut microbes (known as “prebiotics”) are increasingly appreciated as contributing to host health. In particular, positive functional impacts have been observed in both mice and humans following prebiotic intake. A key concern, however, is that there may be no “one-size-fits-all” prebiotic approach for stimulating gut microbiota to enhance human performance. Prebiotics vary in their metabolic effects between people, likely due in large part to inter-individual microbiome differences. Here, David will share his teams work at measuring and predicting the impact of prebiotic therapies on the gut microbiome of humans, as well as impacts on cognition and performance. The findings suggest that prebiotic responses can change with time and are shaped by background dietary choice.

Brief Biography

Lawrence David is an Associate Professor in Duke University’s Department of Molecular Genetics and Microbiology and an Associate Director of the Duke Microbiome Center. The David Lab studies relationships between diet, the gut microbiome, and human health. The lab is also interested in engineering new tools at the interface of nutrition and microbiology. Lawrence has received innovator and young investigator awards from the Burroughs Wellcome Fund, the Beckman, Searle, Sloan, and Damon Runyon Foundations, and he has been named one of the 10 Scientists under 40 years old to watch by Science News. Prior to Duke, Lawrence was a Junior Fellow at Harvard University’s Society of Fellows. He received his Ph.D. in Computational and Systems Biology from the Massachusetts Institute of Technology and completed undergraduate studies in Biomedical Engineering from Columbia University.

Ian Myles, M.D., M.P.H.

Title

Parental Dietary Fat Intake Alters Offspring Immunity in Mice Via the Microbiome

Abstract

Mechanisms underlying modern increases in prevalence of human inflammatory diseases remain unclear. The hygiene hypothesis postulates that decreased microbial exposure has, in part, driven this immune dysregulation. However, dietary fatty acids also influence immunity, partially through modulation of responses to microbes. Prior reports have described the direct effects of high-fat diets on the gut microbiome and inflammation, and some have additionally shown metabolic consequences for offspring. This study sought to expand on these previous observations to identify the effects of parental diet on offspring immunity using mouse models to provide insights into challenging aspects of human health. To test the hypothesis that parental dietary fat consumption during gestation and lactation influences offspring immunity, the team compared pups of mice fed either a Western diet (WD) fatty acid profile or a standard low-fat diet (diets enriched in omega-6 and omega-3 were additional comparators). All pups were weaned onto the control diet to specifically test the effects of early developmental fat exposure on immune development. Pups from WD breeders were not obese or diabetic, but still had worse outcomes in models of infection, autoimmunity, and allergic sensitization. They had heightened colonic inflammatory responses, with increased circulating bacterial LPS and muted systemic LPS responsiveness. All the deleterious impacts of the WD were dependent on the offspring gut microbiome. While numerous other dietary factors play a role in gut health (such as dietary fiber and refined sugars) the data identify a potentially inheritable mechanism for dietary saturated fat consumption to impact offspring immunity.

Brief Biography

Ian Myles, M.D., M.P.H., was born and raised in Colorado. He graduated with a B.S. in biology from Colorado State University in 2001 and then obtained an M.D. from the University of Colorado in 2005. He completed an internal medicine residency at The Ohio State University prior to beginning fellowship training in allergy and clinical immunology at NIH. He worked under the mentorship of Sandip Datta, Ph.D., investigating the mechanistic details of susceptibility to S. aureus skin infections. In 2011, Myles became a commissioned officer in the United States Public Health Service Commissioned Corps. Myles has supported several USPHS missions, from the Ebola virus vaccine trial in West Africa to congressional Gold Medal Ceremonies at the U.S. Capitol, and mass vaccination sites for COVID-19. In 2013, he was awarded a position as an assistant clinical investigator in the NIAID Transition Program in Clinical Research. Myles received his M.P.H. from George Washington University in 2016. In 2018, Myles became the head of the newly formed Epithelial Therapeutics Unit to evaluate the efficacy and safety of a topical, live bacterial treatment for atopic dermatitis (eczema). In 2020, he transitioned to the Lasker Clinical Research Scholars program as well as the Distinguished Scholars Program.

Melanie Gareau, Ph.D.

Title

Developmental Neurotoxicant Exposure and Host-microbe Interactions

Abstract

Host-microbe interactions are critical for maintaining normal physiology of the human host, including the brain and behavior. Bacterial colonization of the gastrointestinal (GI) tract, formation of GI mucosal barrier function, and neurogenesis all occur during a developmental window in early life. Thus, exposure to trauma such as stress, infection, or environmental exposures during neonatal life could detrimentally impact the developing microbiota, gut, and brain (MGB) axis. Disrupted MGB axis signaling, including dysbiosis, mucosal barrier defects and/or changes in behavior, occur in multiple diseases, including inflammatory bowel disease (IBD), autism spectrum disorder, major depressive disorder, and obesity. Environmental exposures to chemicals can result in accumulation over time and can impair health in affected individuals. Early neonatal life is a particularly sensitive period for exposures, potentially impairing rapid growth and development associated with this period. Per- and polyfluoroalkyl substances (PFAS) are a group of man-made chemicals manufactured and used in a variety of industries worldwide since the 1940s. They are very persistent in the environment and in the human body, leading to accumulation over time. Increasing evidence suggests that exposure to PFAS, particularly perfluorooctanoic acid (PFOA), can lead to adverse human health effects, specifically development of IBD, in the elderly. Similarly, a ubiquitous environmental neurotoxicant of considerable interest to both gut and mental health are the class of persistent organic pollutants, known as polychlorinated biphenyls (PCBs). PCBs are one of the few environmental chemicals known to be developmental neurotoxicants in humans, with early life exposures correlated with neurological deficits in children. Despite the ban on their production, PCBs are prevalent in the environment, released as unintentional byproducts of contemporary industrial processes and from old buildings, equipment, and waste facilities. A primary route of exposure of chemicals is via the GI tract through consumption of contaminated foods; however, the impact of PFOA and PCBs on the gut microbiota and potential impacts on intestinal physiology are poorly understood.

Gareau's studies highlight the impacts of environmental exposures on the microbiota, gut, and brain, and suggest that exposures may detrimentally impact host-microbe interactions and subsequently lead to impairments in the brain and behavior.

Brief Biography

Melanie Gareau, Ph.D., is an Associate Professor at the University of California, Davis in the Department of Anatomy, Physiology and Cell Biology in the School of Veterinary Medicine. Her expertise is in intestinal physiology and host-microbe interactions. Her lab researches the development of the microbiota-gut-brain axis using models of enteric bacterial infection, inflammatory bowel diseases and environmental exposures.

Staci Bilbo, Ph.D.

Title

Combined Prenatal Environmental Exposures Impact Brain, Gut, and Microbiome Development in Mice: Implications for Neurodevelopmental Disorders

Abstract

Caroline J. Smith, Danielle N. Rendina, Marcy A. Kingsbury, Staci D. Bilbo.

Gastrointestinal issues are extremely common in neurodevelopmental disorders like autism spectrum disorder (ASD), and alterations of the gut microbiome and intestinal epithelial barrier have been reported in recent studies. Environmental toxicant exposures early in life are increasingly implicated in neurodevelopmental disorders such as ASD, including air pollution. There is strong evidence that particulate matter (PM) in air pollution significantly impacts the gut microbiome and gut function of directly-exposed humans and rodents. Less characterized is if PM exposure to pregnant females alters the gut microbiome of offspring.

To study the impact of environmental pollutants on autism-like behaviors in mice, Bilbo and her team developed a novel model combining prenatal diesel exhaust particle (DEP) exposure throughout pregnancy with maternal stress (MS) during the last trimester of gestation. Maternal stress is linked to autism in several recent studies, which may be most harmful for populations made vulnerable by other factors. The team has demonstrated that combined prenatal DEP + MS produce striking communication and social deficits early in life, and persistent neuroimmune changes, in male but not female offspring. The data also show significant changes in the composition of gut bacteria and gut structural changes in male offspring exposed prenatally to DEP/MS compared to unexposed controls. Moreover, colonization at birth with a healthy microbiome rescues normal social behavior in male offspring.

The goal of this project going forward is to test the hypothesis that gut microbiome changes in pregnant dams following combined environmental exposures are transmitted to newborn offspring and underlie the persistent brain and behavioral abnormalities in males. Surprisingly, no changes in the gut, vaginal, or milk microbiomes of exposed dams were found. Thus, the team is currently testing the hypothesis that gut epithelial changes that begin prenatally, e.g., in response to maternal immune activation/inflammation, underlie differential microbial colonization postnatally, and thereby present a novel opportunity for intervention and therapeutics.

Brief Biography

Staci Bilbo, Ph.D., is a Professor of Psychology and Neuroscience, Neurobiology, and Cell Biology at Duke University whose research is broadly focused on the mechanisms by which the immune and endocrine systems interact with the brain to impact health and behavior, particularly during critical developmental windows. Her research program is primarily aimed at exploring the mechanisms by which innate central nervous system immune cells-microglia-and signaling molecules such as cytokines and chemokines, influence both normal and abnormal brain development, and the implications for (mal)adaptive behavioral outcomes later in life, including a focus on neurodevelopmental disorders such as autism spectrum disorder. Bilbo received her B.A. in Psychology and Biology from the University of Texas at Austin and her Ph.D. in Neuroendocrinology at Johns Hopkins University. She was on the faculty at Duke University from 2007-2015before she joined the faculty at Harvard where she served as the Lurie Family Associate Professor of Pediatrics and Neuroscience at Harvard Medical School and as the Director of Research for the Lurie Center for Autism at Massachusetts General Hospital for Children. She returned to Duke in 2019 as the Haley Family Professor of Psychology and Neuroscience and maintains an appointment at Harvard to continue her research collaborations in Boston and beyond.

Beate Ritz, M.D., Ph.D.

Title

Pesticides, Parkinson’s disease, and the Microbiome in the California Central Valley

Abstract

The neurodegenerative disorder Parkinson's disease (PD) may not start in the brain but - at least in some cases - in the gut. It has been suggested that microbial metabolites affect the gut-brain axis or that gut microbes contribute to neurodegeneration through inflammatory processes. Among environmental agents, pesticides have been most consistently shown to increase the risk of PD. Pesticides are toxins that are intentionally introduced into the environment to harm organisms and many are designed to be neurotoxic. In addition to being toxic to brain cells, however, pesticide may also affect the composition or function of gut microbiota as they may be either toxic or advantageous to certain microbes. As pesticides are an important component of agriculture worldwide and their use is growing, it is paramount to assess how exposures may affect those living and working in close proximity to treated fields. Here, Ritz will present the study's rational and briefly give an overview of what is known about PD and pesticides with examples of exposure assessment methods, gene-environment and omics approaches that were used in an ongoing two-decades long study in California. Then, Ritz will present the teams latest approach and preliminary results comparing gut microbiome profiles and function due to PD or pesticide exposures in study participants from central California, a heavily agricultural region with high pesticide use. Finally, Ritz will discuss next steps such as further exploring the metabolic function of gut microbiota related to pesticide exposures.

Brief Biography

Beate Ritz, M.D., Ph.D., is a Professor of Epidemiology at the UCLA Fielding School of Public Health with co-appointments in Environmental Health Sciences and Neurology at the UCLA, SOM; and a member of the Center for Occupational and Environmental Health. For a decade, she co-directed the NIEHS-funded Center for Gene-Environment (GxE) in Parkinson’s disease (PD) at UCLA targeting occupational and environmental toxins such as pesticides in relation to Parkinson’s disease. She collaborates with neuroscientists, human geneticists, and clinicians at UCLA. She has been the PI of two large population-based case control studies of PD in Denmark (PASIDA study with 3600 participants) and in California’s central valley the long-running Parkinson, Environment and Genes (PEG) study that started collecting data from 1,870 PD patients and controls in the year 2000. For PEG, Ritz’ team has also collected and stored bio-samples (blood, serum, plasma, saliva, urine, fecal matter) and recorded longitudinal motor and non-motor progression in the PD patients over a decade of follow-up. Her lab has collected genetic, genomics, epigenetic, metabolomics, questionnaire and clinical phenotyping and progression data for PEG study participants enrolled between 2001 and 2018with progressive updates of patients’ status; most recently her team started collecting fecal samples form study participants. She served on multiple IOM committees evaluating ‘Gulf War Illnesses’, ‘Health Effects of Veterans from Herbicide Exposures in Vietnam’, and ‘Incorporating 21st Century Science into Risk-Based Evaluations’, the U.S. EPA CASAC panel (Carbon Monoxide NAAQS); and currently is a member of the Scientific Review Panel on Toxic Air Contaminants for the state of California. In 2008, she received are search Award from the American Parkinson’s Disease Association and she made the Clarivate list of most highly-cited authors list in 2018. In 2018, she was elected President of the International Society for Environmental Epidemiology.

Thomas Sharpton, Ph.D.

Title

High-throughput Approaches Can Demystify Exposure-microbiome-behavior Interactions

Abstract

Recent discoveries have elevated the hypothesis that gut microbes can mediate how environmental exposures influence neurophysiology and behavior. However, the ability to explore this hypothesis is complicated by the vast diversity and variation of the exposome and gut microbiome. Innovations in high-throughput experimental resources can fortunately enable rapid screens that help pin-point specific exposures that interact with microbiota to elicit neurophysiological effects. In this presentation, Sharpton summarizes one powerful example of such a resource – the zebrafish model system – which affords access to large sample sizes, automated exposure and phenotyping platforms, and short generation times. Sharpton also discusses analytical and experimental tools, including metagenomic gene catalogs and high-throughput gnotobiotic fish assays, which Sharpton and team have innovated to uncover the mechanisms through which the microbiome interacts with exposure and mediates its physiological effects. Finally, Sharpton discusses how his team has used this system to determine the effect of benzo[a]pyrene exposure on gut microbiome assembly and the impact of these effects on neurodevelopment.

Brief Biography

Thomas Sharpton, Ph.D., is an Associate Professor of Microbiology and Statistics at Oregon State University (OSU). He obtained a Ph.D. in Microbiology from the University California at Berkeley, and subsequently trained at the Gladstone Institutes as a postdoctoral fellow. He joined OSU as a faculty member in 2013 and has since developed an internationally recognized research program that uses systems biology methods to resolve the gut microbiome’s influence on the health and behavior of vertebrates. His lab is especially known for developing strategies for the analysis of microbiomic and metagenomic data as well as the integration of data across study systems ranging from fish to humans. He has published over 60 manuscripts, edits and advises fora variety of microbiology and systems biology research journals, and serves as the founding director of the OSU Microbiome Initiative.