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Transcript
February 10th-11th 2016 | San Diego, California, USA Welcome to the Human Microbiome Congress 2016 From Structure to Function: Examining function in the human microbiome. Part of Kisaco Research’s global conference portfolio Conference Day One: Wednesday February 10th, 2016 08:30 Registration for Conference and Exhibition Hall Opens for All Attendees 09:00 Chairperson’s Opening of Conference Part 1: Characterising the Normal/Healthy Human Microbiome 09:10 Exploring the Role of the Microbiome in Disease Dr. Weinstock will discuss how the complex microbial communities that make up the human microbiome are highly-integrated with the human body and can change with different health states and may well cause such changes. The task of finding such causal relationships requires good sample sets as well as many analysis approaches. Possible causal mechanisms could operate at the ensemble level, or be due to changes in single organisms, or in multiple organisms. A number of such examples will be presented. George Weinstock, The Jackson Laboratory 09:40 The Perinatal Microbiome and Pregnancy: Moving Beyond the Vaginal Microbiome The human microbiome, the collective genome of the microbial community that is on and within us, has recently been mapped. The initial characterization of healthy subjects has provided investigators with a reference population for interrogating the microbiome in metabolic, intestinal, and reproductive health and disease states. Although it is known that bacteria can colonize the vagina, recent metagenomic studies have shown that the vaginal microbiome varies among reproductive age women. Similarly, the richness and diversity of intestinal microbiota also naturally fluctuate among gravidae in both human and nonhuman primates, as well as mice. Moreover, recent evidence suggests that microbiome niches in pregnancy are not limited to maternal body sites, as the placenta appears to harbor a low biomass microbiome that is presumptively established in early pregnancy and varies in association with a remote history of maternal antenatal infection as well as preterm birth. In this article, we will provide a brief overview on metagenomics science as a means to investigate the microbiome, observations pertaining to both variation and the presumptive potential role of a varied microbiome during pregnancy, and how future studies of the microbiome in pregnancy may lend to a better understanding of human biology, reproductive health, and parturition. Amanda Prince, Baylor College of Medicine 10:10 Functionality of the Vaginal Microbiome in Reproductive Health Progress has been made in recent years to characterize the vaginal microbiome composition in women of reproductive age. Recent studies have further identified a shift in microbiome composition during pregnancy towards a community with lower diversity, in which lactobacilli are enriched and anaerobic organisms associated with bacterial vaginosis are excluded. Bacterial vaginosis, a dysbiosis of vaginal flora, impacts approximately one in three women at any given time and is associated with pregnancy complications including preterm birth occurring before 37 weeks gestation. Ascending infection of Presented by: For Sponsorship Opportunities, email [email protected] For Programme Questions, email [email protected] February 10th-11th 2016 | San Diego, California, USA bacterial species originating in the vagina has emerged as a mechanism estimated to contribute to 4050% of preterm births. This presentation will address what has been learned so far, and where future investigations might take us. 10:40 Jennifer Fettweis, Virginia Commonwealth University Interrogation and Characterization of Bacterial Proteins of the Human Gut Microbiome: Our goal is to expand on the pioneering metagenomic sequencing and metabolomic methodologies with the development and application of new chemical biology tools, mass spectrometry metaproteomic methods, and bioinformatic search algorithms as techniques to identify and quantitate gut bacterial proteins. We present a modified functional metaproteomics approach that employs activity-based probes (ABPs) to directly measure, characterize, and quantitate gut microbial proteins and their enzymatic functions. Biotin-containing small molecule ABPs are added to microbiome samples to covalently label and isolate individual protein families from the complex gut microbial proteome in a rapid and throughput manner. We target the identification of secreted and surface expressed hydrolases, proteases, and glycosidases, as these enzymes are at the microbiome interface and are likely key players in the crosstalk between the host and bacteria. All ABP-labeled proteins are subjected to high performance reverse phase liquid chromatography coupled with tandem mass spectrometry for protein identification. Ultimately, our goal is to elucidate the normal distribution of gut bacterial proteins among individuals (if one exists), identify which protein functionalities are essential for human homeostasis, and determine what proteins and interactions with the host are altered or compromised in dysbiosis. The results from our work will facilitate the discovery of chemical and biological tools to probe the roles that key enteric bacterial enzymes play in human health and microbiome-related diseases. Importantly, our new methods and materials will provide a foundation for further development of metaproteomic approaches to target a variety of key protein functionalities within human microbiomes. 11:10 Dennis Wolan, The Scripps Research Institute. Morning Networking Break: Coffee, Tea & Refreshments for All Attendees 11:40 Searching Beyond the Lamppost: New Protein Families Dominate in Newly Explored Environments Adaptation of the human gut microbiome to its unique environment is typically described in terms of the relative composition and diversity of microbial species. An alternative (and complementary) perspective can provided by analyzing the relative distribution of protein families in metagenomic datasets. While it was noticed in literature (Yooseph, 2007; Qin, 2010) that microorganisms living in these newly studied envirnoments contain many novel, uncharacterized proteins and that these proteins form families, such families were never defined nor submitted to public domain databases (Finn, 2014). We performed analysis of protein families distributions in the MetaHIT, currently the largest single dataset for the human gut microbiome. We found about 300 highly overrepresented protein families, with top 100 similarly overrepresented in all human metagenomics sets. Interestingly, most of them are uncharacterized (Goodacre, 2013) and moreover, most were defined only recently. Similar analysis performed even few years ago would artificially downplay the uniqueness of the human gut Presented by: For Sponsorship Opportunities, email [email protected] For Programme Questions, email [email protected] February 10th-11th 2016 | San Diego, California, USA microbiome, as distribution of well characterized protein families is similar to that in well studied bacterial species. By large scale structure determination and distant homology analysis we assigned putative functions to most of the overrepresented protein families (Figure 1). We show that protein families overrepresented in the the gut microbiome are related to secretion, motility and chemotaxis, also that surprisingly large percentage of them are extracellular. We compare those to the set of overrepresented protein families in the the ocean micobiome, which contains more families with functions linked to cell wall and outer membrane structure and biogenesis. These differences can be rationalized by the need for very efficient nutrient intake mechanisms in the ocean due to the relative shortage of nutrients while, in the human gut, the relative abundance of nutrients, high density of microorganisms and presence of the host immune system require more proteins for protein-protein and protein-carbohydrate interactions. Full characterization of large sets of proteins, such as derived from metagenomic sequencing projects require better libraries of protein families, which would correctly represent the wide variety of novel proteins found in the newly characterized environments. Significant number of protein families in the latest Pfam release provide such representation, allowing us to identify dominant protein families in human gut and ocean environments. Adam Godzik, Sanford Burnham Prebys Medical Discovery Institute 12:10 Structure and Function of the Cystic Fibrosis Lung Microbiome Cystic Fibrosis (CF) is a genetic disease that results in buildup of thick mucus in the lung that becomes infected with opportunistic pathogens, most famously, Pseudomonas aeruginosa. Molecular methods have revealed that CF lungs are infected with a more diverse microbial community than is appreciated by clinicians, highlighting the need for a more comprehensive understanding of CF microbial ecology. Our group has been studying the physiology and dynamics of the CF microbial community focusing on CF exacerbations, which are events of CF disease characterized by an increase in symptom severity. Omics methods such as metagenomics, transcriptomics, and metabolomics have led to a new understanding of how the core physiology of CF bacteria governs community dynamics and, potentially, their involvement in exacerbations. With a variety of methods we have observed that as an exacerbation develops the CF microbial community is actively fermenting. This fermentation is done by lesser-known CF pathogens, the anaerobes. Antibiotic treatment wipes out this fermentative community, explaining treatment efficacy. Co-occurrence networking of 16S rDNA microbiome and metagenomic data identified the existence of two functional communities in the CF lung. These were a community of classic CF pathogens (ie. P. aeruginosa) utilizing respiration and consuming amino acids, and a fermentative community, comprised of mostly oral anaerobes. These two different communities have contrasting effects on the pH of the lung environment. The fermentative community lowers the lung pH and the respiratory community raises it. Our findings have led to a new hypothesis about how the CF microbial community is governed by its own physiology and exists in stable and disturbed states, much like those in classical ecology. This study demonstrates how the core metabolism of a microbial community governs its structure and dynamics. Robert A. Quinn, UCSD 12:40 Complex Carbohydrate Degradation by Human Gut Bacteria During Health and Disease The trillions of symbiotic microorganisms in the human gut expand our digestive physiology by providing an armament of polysaccharide-degrading enzymes that are absent in the human genome. Presented by: For Sponsorship Opportunities, email [email protected] For Programme Questions, email [email protected] February 10th-11th 2016 | San Diego, California, USA Dietary polysaccharides, mixed with endogenous mucosal secretions, present a diverse menu of complex carbohydrates that our gut symbionts have adapted strategies to sense, triage and degrade. Understanding which species consume each nutrient, how abilities vary among taxa and what the molecular mechanisms involved are, represent central problems in defining the relationship between diet, microbiota and health. We are taking microbiological, genomic, genetic and biochemical approaches to address these problems. Our results have revealed that members of the phylum Bacteroidetes are major contributors to carbohydrate digestion and rely on expression of discrete gene clusters that each encodes the requisite proteins to catabolize a particular polysaccharide. Expression of each gene cluster is activated by a locally encoded transcription factor that participates in carbohydrate sensing and metabolism until its supply is exhausted. In the context of a single bacterium, many dozen individual gene clusters may simultaneously be triggered to respond to available nutrients. Yet, in experimental conditions in which such complex nutrient environments are modeled, there is an ordered progression of carbohydrate utilization that is reminiscent of catabolite repression. Of central focus in our studies is the interplay between dietary fiber polysaccharides and mucosal glycans. Some bacteria possess mechanisms to suppress utilization of mucosal glycans when dietary alternatives are present, while others exhibit opposite behavior. Our results reveal that sensing and triaging of glycans is a complex process that varies among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms commit to various niches in a constantly changing nutritional environment. Eric C. Martens, University of Michigan 13:10 Networking Lunch 14:30 Armpit Microbiome: Why Should We Care? Microbes that live on our skin, in particular in our armpits, affect us on a daily basis and provide one of the main reasons for bathing daily and using fragrances including underarm products. Body odor, on humans and other animals, affects interactions with others, informs selection of a mate and predisposes animals to mosquito bites, significant vectors of disease (Verhulst, 2011). Through an examination of the primate armpit microbiome including humans, chimpanzees, gorillas, baboons and rhesus macaques, we assessed the relative abundance and diversity of armpit microbes. Human armpits not only have the lowest number of OTUs but also the lowest diversity among tested primates, leading to a microbiome that is structurally unique from other primates. To further investigate the effect of our unique skin microbiome on odor and attractiveness, we conducted a citizen science project to combine odor assessment with 16S rRNA sequencing to determine bacterial composition and its potential correlation with odor. In our study we collected volatile organic compounds (mVOCs), presumably produced by bacterial metabolism of apocrine gland secretions, in addition to worn T-shirts from our participants. With the T-shirts (worn nightly by participants who had gone two days or more days without underarm product), we conducted a “Speed Smelling” event where participants smelled T-shirts and rated the overall smell, odor intensity and attractiveness. Analysis of these complementary datasets will allow for correlations between odor and the microbes living on skin, and will allow us to draw larger conclusions about odor and mate selection. Presented by: For Sponsorship Opportunities, email [email protected] For Programme Questions, email [email protected] February 10th-11th 2016 | San Diego, California, USA Sarah Council, North Carolina Central University 15:00 A Member of the Microbiota Modulates Host Metabolism to Increase Intestinal Permeability and Disease The commensal microbiota has important impacts on host physiology and health that are only beginning to be elucidated. Most current studies, however, have focused only on the bacterial microbiota despite the presence of fungal, archaeal and viral members. The presence of antiSaccharomyces cerevisiae (ASCA) antibodies has long been a prognostic tool for Crohn’s disease (CD) and suggests that fungal members of the microbiota contribute to the course of disease severity. Here we report that fungal members of the human microbiota, S. cerevisiae but not R. aurantiaca, can exacerbate intestinal disease and increase gut barrier permeability. Transcriptome analysis of germfree animals mono-associated with S. cerevisiae or R. aurantiaca revealed that yeast colonization most robustly impacted intestinal barrier and metabolism. Indeed, animals colonized with S. cerevisiae have greater intestinal leakage during colitis and increase permeability of intestinal epithelial cell lines. A fecal metabolomic screen from germfree mice mono-associated with S. cerevisiae or R. aurantiaca demonstrated that S. cerevisiae colonization enhanced host purine metabolism leading to greater uric acid production. Elevated levels of uric acid are detected in the serum of animals colonized with S. cerevisiae during colitis. Treatment with uric acid alone is sufficient to induce worsened disease and increase gut permeability. Importantly, animals treated with allopurinol, a clinical drug used to reduce uric acid levels, protects from worsened colitis. Supporting our data in mice, there is a significant positive correlation between elevated uric acid and ASCA antibodies in human sera. Thus, intestinal yeast species can potentiate oxidative metabolites to negatively impact the course of IBD and highlights the importance of this kingdom to host health. June Round, University of Utah School of Medicine 15:30 Carbohydrate Utilization in Human Gut Bacteria The human gut microbiome harbors a large number of microbes forming a complex community that greatly affects the physiology and pathology of the host. The gut microbiome performs a diverse set of functions supplementing those performed by the host and is believed to significantly enhance the metabolism of amino acids, carbohydrates, xenobiotics, methanogenesis, biosynthesis of vitamins and other compounds. Therefore, microbiomes represent a potential pool of genes coding for novel proteins and functions. However, a large number of microbiome species are poorly characterized or unculturable. Carbohydrate metabolism plays a crucial role in the ecophysiology of human gut microbiota. We have analyzed gut microbiome sequence data to identify novel, previously uncharacterized protein families. The analysis revealed an abundance of enzymes involved in carbohydrate metabolism such as glucoside hydrolases of dietary polysaccharides and glycoconjugates. Some bacterial α-glucosidases are structural homologues to human intestinal maltase-glucoamylase with a highly conserved catalytic domain and reduced auxiliary domains. Some enzymes can utilize several small-mass neutral human milk oligosaccharides which are fucosylated. The crystal structure of GH29 α-L-fucosidase reveals a structure that is similar to previously characterized fucosidases and can process fucosylated oligosaccharides. Mechanisms of transcriptional regulation of carbohydrate catabolism in commensal and prevalent human gut bacteria remain mostly unknown. Members of a new family of transcription factors NrtR act as novel regulators controlling the arabinose utilization genes in Bacteroides species. Structures of apo-protein and complexes with a sugar and a specific DNA operator revealed ligand-mediated regulatory mechanism. Our analysis facilitates reconstruction of the metabolic and regulatory networks involved in carbohydrate utilization in human gut Bacteroides. Presented by: For Sponsorship Opportunities, email [email protected] For Programme Questions, email [email protected] February 10th-11th 2016 | San Diego, California, USA Andrzej Joachimiak, Argonne National Laboratory 16:00 Afternoon Networking Break: Coffee, Tea & Refreshments for All Attendees Part 2: Functions of the Human Microbiome 16:30 Bacteriophage Adherence to Mucus (BAM) Immunity: How Phage and the Microbiome form Innate and Acquired Immune Systems on Mucosal Surfaces Bacteriophage Adherence to Mucus (BAM) Immunity is a novel, microbiome-derived, phagemediated immunity active at mucosal surfaces. Phage stick to mucin glycoproteins via hypermutable, immunoglobulin-like domains displayed on their capsids and protect the underlying epithelial cells from invading bacteria. The complexity of these interactions between phage, microbes and the macrobial host are just starting to be de-convoluted. Using an organ-on-a-chip approach, we show that mucus-binding phage have a subdiffusive hunting pattern that resulted in more frequent host interactions than non-mucus-adherent phages moving by normal Brownian diffusion. A supporting theory and experiments show that subdiffusion as a more efficient phage search strategy at low bacterial concentrations found deeper within mucus layers. These findings extend previous observations that phage form an acquired and adaptive immune system on mucosal surfaces and for phage manipulation of microbiomes. 17:00 Forest Rohwer, San Diego State University Imaging Microbial Nutrient Acquisition in the Plant Microbiome One of the key challenges in microbial ecology is determining the ecophysiology of microorganisms in complex communities. Isotope-labeling experiments provide a powerful means to directly measure the activities of uncultivated microbes in-situ, as well as quantitatively measure nutrient transfers between cell types, symbionts and consortia. We are using novel stable isotope techniques to track microbial nutrient acquisition in the plant rhizosphere, which is the portion of the plant microbiome that directly surrounds plant roots in soil. The rhizosphere is loosely analogous in function to the human gut, where the plant acquires the majority of its nutrients in collaboration with the surrounding soil microbial community. In this zone, we can track the movement of carbon and nitrogen between the plant host and microbial community using the stable isotopes 13C and 15N, as well as the fate of these compounds in the soil matrix. To do so, our group has developed 'Chip-SIP', which combines nanometer-scale isotope imaging using NanoSIMS with phylogenetic microarrays to determine the isotopic enrichment of microbial populations. Using this isotope array, we have tracked movement of 13C from labeled plant exudates and 15N from labeled root litter into the soil microbial community (bacteria, fungi, microfauna), and linked this data to 16S profiles and gene transcripts. We have also used NanoSIMS to directly image microbial cells in-plantae, where we’ve documented the transport of 15N by a symbiotic fungi (arbuscular mycorrhizae) to the host plant. We’re currently using this method with isotopically-labeled water (H218O), which allows us to detect and characterize all active microorganisms, as water is universally required by microorganisms for activity. Finally, we are using spatially resolved spectroscopy (STXM/NEXAFS) to determine the chemical fate of microbial cells in soil, which allows us to classify the compounds sorbed to minerial surfaces at the nanometer scale (e.g., lipids, amino sugars, phospholipids). These techniques allow precise, high-resolution, quantitative measurement of molecular and isotopic patterns in undisturbed samples, and are equally promising techniques for studying host-microbe and microbe-microbe interactions in the human microbiome. Presented by: For Sponsorship Opportunities, email [email protected] For Programme Questions, email [email protected] February 10th-11th 2016 | San Diego, California, USA Jennifer Pett-Ridge, Lawrence Livermore National Laboratory 17:30 Metagenomic Assembly and Strain-Level Tracking of the Fecal Resistome Assemblages of genes that encode resistance to antibiotics within human, animal, insect and environmental metagenomes are known as “resistomes”. Healthy human gut resistomes have been described from the metagenomes of the Human Microbiome and MetaHIT Projects, Yanomani Amerindians, Hadza Hunter-Gathers and others. While most studies report resistance potential as a tally or fraction of antibiotic resistance genes within a metagenome, we are using deep metagenomic sequencing and assembly, combined with resistance gene annotation to map antibiotic genes to specific genomes within a fecal sample. Further, we are associating resistance genes with mobile genetic elements on these genomes. Our goal is to identify genetic exchange communities of elements and organisms capable of spread of antimicrobial resistance. Sarah K. Highlander, J. Craig Venter Institute, La Jolla, CA 18:00 Close of Conference Day One Networking & Welcome Reception for All Attendees POSTER SESSION Conference Day Two: Thursday February 11th, 2016 08:30 Registration for Conference and Exhibition Hall Opens for All Attendees 09:00 Conflict Food – Do Genetic Conflicts of Interest between Host and Microbiome Explain the Health Impacts of Junk Food? Humans have a complex relationship with the multitudes of genomes that make up the microbiome. Cooperation between host and commensal microbes is important in preventing pathogens from establishing an infection. Conflicts between the human genome and microbiome, on the other hand, may contribute to chronic diseases such as obesity and metabolic syndrome. Because foods have powerful and predictable effects on microbiota composition and function, they may also drive cooperation or conflict in the microbiome. The conflict food hypothesis proposes that unhealthy foods cause increasing divergence of fitness interests between host and microbiome. With this perspective, conflict foods are those that select for exploitative populations of microbes that increase their fitness at the expense of their host’s fitness. Healthy foods are those that select for microbial communities and functions that are aligned with and promote human fitness. This presentation investigates the evidence for the conflict food hypothesis and its implications for nutrition and public health. Joe Alcock, University of New Mexico 09:30 Diversity and Function of the Skin Microbiome The human skin harbors an abundant microbial ecosystem with bidirectional metabolic exchanges supporting symbiotic and commensal functions. Sequence- based analysis of microbial community structure and organization of the human microbiome has yielded valuable insight into the microbial Presented by: For Sponsorship Opportunities, email [email protected] For Programme Questions, email [email protected] February 10th-11th 2016 | San Diego, California, USA diversity and function of its different body niches. Metagenomic analyses of the diverse skin sites in healthy humans demonstrate that contrasting forces of the skin’s biogeography and individual characteristics shape the skin microbiome and the dynamics of its bacteria, fungi, and viruses. However, shifts in the ecological properties of the skin microbiome are significantly associated with skin disease, disease severity, and other physiologic host factors such as age or primary immunodeficiency. Understanding the function, structure, and dynamics of the microbiome is important to design therapeutics that precisely target the pathogen of interest, yet spare the surrounding beneficial microbiota. 10:00 Julia Oh, The Jackson Lab Establishing Causal Connections between Gut Microbiota Composition and Human Disease The composition of the gut microbiota is thought to have dramatic effects on the development and progression of a variety of diseases. However, identifying the specific bacteria that preferentially affect disease susceptibility and severity in humans remains a major challenge. In response to this problem, we recently developed a novel technology that uses the host’s own immune response to the microbiota as a guide to identify specific members of the gut microbiota that preferentially modulate disease development. Using this approach, we could identify and isolate specific bacterial strains from IBD patients that selectively conferred susceptibility to severe colitis when transplanted into germfree mice. These studies thus: (i) establish a new strategy for the identification of disease- and immune-modulating members of the microbiota in humans; (ii) identify potentially disease-driving members of the intestinal microbiota in humans with IBD; and (iii) begin to establish causal, rather than correlative, connections between specific changes in the microbiota and human disease. Future studies using similar approaches will allow us to elucidate the precise role of microbiota composition in human health and disease, and will eventually enable the development of novel and specific microbiota-targeted therapeutics. Noah W. Palm, Yale University School of Medicine 10:30 New Proteomic Insights into Host-Microbe Interactions The intestinal microbiota have profound and diverse effects on host physiology, but the precise nature of host-microbe interactions remains difficult to measure. Specific microbial sub-populations, enumerated through 16S sequencing, are often correlated with health and disease states. This approach cannot directly report dynamic host responses to perturbations to the microbiota as mediated by diet, pharmaceuticals, or opportunistic infections, however. We previously developed a mass spectrometry technique, “host-centric proteomics of stool,” which directly measures proteins secreted or shed into the GI in response to changing intestinal ecosystems. With this approach, we quantified host responses to antibiotic-associated infections in mice, and are extending these observations to humans. These efforts are enhanced by novel software we developed which enables unprecedented depths of protein discovery from virtually any organism, even in the absence of paired metagenomic sequencing. With it, we are able to quantify dynamic host, microbial and dietary interactions directly from stool. Josh Elias, Stanford University, USA 11:00 Morning Networking Break: Coffee, Tea & Refreshments for All Attendees 11:30 Activity-Based Protein Profiling of Drug Metabolism in the Gut Microbiome Presented by: For Sponsorship Opportunities, email [email protected] For Programme Questions, email [email protected] February 10th-11th 2016 | San Diego, California, USA The broad diversity of microbes residing in the human body greatly extends the synthetic and metabolic capacity of the human genome. Emerging studies also show the diverse metabolic functions encoded by trillions of microbes within the intestinal tract can mediate the chemical transformation of xenobiotics, such as pharmaceuticals and environmental contaminants associated with energy production. Still, the impact that xenobiotic exposures have on the microbiome, and in turn how perturbed microbiomes influence host susceptibility to environmental or drug agents is poorly understood, yet may be a critical component of individual variability to xenobiotic toxicity, drug bioavailability, efficacy, and interactions. In our research, we are using activity-based protein profiling to evaluate the hypothesis that perturbations in the composition of the gut microbiome influence susceptibility by altering host metabolic capacity toward xenobiotics. Our approach enables the direct measurement of functionally active enzymes of the host and microbiome important to drug metabolism and disposition. Due principally to the high complexity of mammalian microbiomes, our understanding of their specific protein activities is largely based on inference from metagenomics and transcriptomic data. Activitybased probes (ABPs) we have or are developing offer the potential to transform this approach, by permitting the direct and selective capture and fluorescence imaging or proteomic profiling of the metabolically active subset of microbes and proteins within the microbiome. Aaron Wright, PNNL 12:00 Antibiotics, Pedatric Dysbiosis, and Disease Antibiotics are by far the most common medications prescribed for children. Recent epidemiological data suggests an association between early antibiotic use and disease phenotypes in adulthood. Antibiotic use during infancy induces imbalances in gut microbiota, called dysbiosis. The gut microbiome’s responses to antibiotics and its potential link to disease development are especially complex to study in the changing infant gut. Here, we synthesize current knowledge linking antibiotics, dysbiosis, and disease and propose a framework for studying antibiotic-related dysbiosis in children. We recommend future studies into the microbiome-mediated effects of antibiotics focused on four types of dysbiosis: loss of keystone taxa, loss of diversity, shifts in metabolic capacity, and blooms of pathogens. Establishment of a large and diverse baseline cohort to define healthy infant microbiome development is essential to advancing diagnosis, interpretation, and eventual treatment of pediatric dysbiosis. This approach will also help provide evidence-based recommendations for antibiotic usage in infancy. 12:30 Dan Knights, University of Minnesota Intestinal Microbial Communities Associated with Acute Enteric Infections and Disease Recovery The intestinal microbiome represents a complex network of microbes that are important for human health and preventing pathogen invasion. Studies that examine differences in intestinal microbial communities across individuals with and without enteric infections are useful for identifying microbes that support or impede intestinal health. 16S rRNA gene sequencing was conducted on stool DNA from patients with enteric infections (n = 200) and 75 healthy family members to identify differences in intestinal community composition. Stools from 13 patients were also examined post-infection to better understand how intestinal communities recover. Patient communities had lower species richness, evenness, and diversity versus uninfected communities, while principle coordinate analysis demonstrated close clustering of uninfected communities, but not the patient communities, irrespective of age, gender, and race. Differences in community composition between patients and family members were mostly due to variation in the Presented by: For Sponsorship Opportunities, email [email protected] For Programme Questions, email [email protected] February 10th-11th 2016 | San Diego, California, USA abundance of phyla Proteobacteria, Bacteroidetes, and Firmicutes. Patient communities had significantly more Proteobacteria representing genus Escherichia relative to uninfected communities, which were dominated by Bacteroides. Intestinal communities from patients with bloody diarrhea clustered together in the neighbor-joining phylogeny, while communities from 13 patients’ postinfection had a significant increase in Bacteroidetes and Firmicutes and clustered together with uninfected communities. These data demonstrate that the intestinal communities in patients with enteric bacterial infections get altered in similar ways. Furthermore, preventing an increase in Escherichia abundance may be an important consideration for future prevention strategies. Rob Britton, Baylor College of Medicine 13:00 Networking Lunch Part 3: Applications of the Human Microbiome 14:30 Restoring and Preserving Man-Microbe Symbiosis Man builds as a microbe-host symbiosis from birth on. Maintenance of symbiosis is key to the preservation of its health and well-being. Yet this recognition comes after more than 60 years during which our microbiota has had to cope with drastic changes in birth management, nutrition and clinical practices. This has come with an uncontrolled increase in incidence of immune-mediated diseases. As we get to recognize dysbiosis as an alteration of man-microbe symbiosis, “how to preserve and restore man microbe symbiosis?” is a very timely question. As a central component of human health, the intestinal microbiome may help in several ways that we will illustrate: 1: as a stratifying tool for personalization of nutrition and therapies, allowing to account for non-responders as well as predicted risk of onset and aggravation of chronic disorders, i.e. via quantitative metagenomics. 2: as a source of novel drugs and drug-targets, i.e. via functional metagenomics unraveling novel microbe-cell crosstalk mechanisms 3: as a target for modulation, aiming at a preventive or curative outcome, i.e. via functional nutrition 4: as a drug of its own, as per organ transplantation, for ecological restoration, management of infectious risk or prevention of dissemination of resistance. Metagenomics has revolutionized our perception of the importance of the intestinal microbiota for human health and yet more is needed to eventually get the most from our gut. Joel Doré, INRA 15:00 Fermented Foods as Experimentally Tractable Microbial Ecosystems Microbial communities of fermented foods have provided humans with tools for preservation and flavor development for thousands of years. These simple, reproducible, accessible, culturable, and easy-to-manipulate systems also provide opportunities for dissecting the mechanisms of microbial community formation. Fermented foods can be valuable models for processes in less tractable microbiota. Presented by: For Sponsorship Opportunities, email [email protected] For Programme Questions, email [email protected] February 10th-11th 2016 | San Diego, California, USA Rachel Dutton, UCSD 15:30 Developing Predictive and Prognostic Markers for Wound Healing Wound-healing is still a complex area. We look into the different contributions to infection-related complications and poor healing apparent in acute and chronic wounds, with particular focus on microbial load, microbial diversity and pathogenic microorganism (bioburden). We have found that standard cultures offer little predictive or prognostic value for wound outcomes, and better biomarkers are needed to guide management and treatment of both acute and chronic wound patients. We have begun longitudinal studies employing culture-independent approaches and the incorporation of patient clinical data which have the potential to provide more precise information on how wound microbiomes evolve during the healing process, and also predict specific outcomes – such as rate of healing or progression to infection-related complication. Elizabeth Grice, University of Pennsylvania 16:00 Afternoon Networking Break: Coffee, Tea & Refreshments for All Attendees 16:30 Molecular Cartography of the Human Skin Surface in 3D The human skin is an organ with a surface area of 1.5–2 m2 that provides our interface with the environment. The molecular composition of this organ is derived from host cells, microbiota, and external molecules. The chemical makeup of the skin surface is largely undefined. Here we advance the technologies needed to explore the topographical distribution of skin molecules, using 3D mapping of mass spectrometry data and microbial 16S rRNA amplicon sequences. Our 3D maps reveal that the molecular composition of skin has diverse distributions and that the composition is defined not only by skin cells and microbes but also by our daily routines, including the application of hygiene products. The technological development of these maps lays a foundation for studying the spatial relationships of human skin with hygiene, the microbiota, and environment, with potential for developing predictive models of skin phenotypes tailored to individual health. Pieter Dorrestein, UCSD 17:00 The Microbiome-Gut-Brain Axis in Autism The microbiome-gut-brain axis has been implicated in behavioral disorders as well as functional gastrointestinal (GI) disorders. While GI symptoms are a significant comorbidity in children with autism spectrum disorder (ASD) and may contribute to problem behaviors, microbiome studies in individuals with autism are hampered by multiple confounders that have yielded conflicting results. Consequently, there is growing interest in defining the role of the microbiome in ASD development, especially in early childhood when establishment of the gut microbiome and manifestations of clinical ASD symptoms occur concurrently. The identification of GI issues remains difficult in the ASD population and in particular the children with limited verbal communication. The development of stool-based biomarkers would represent a vital tool for both physicians and children with ASD. Microbiome characterization of GI specimens in children with autism will be discussed and compared to unaffected siblings, healthy children, and children with functional GI disorders. The identification of pathophysiologic mechanisms that link disturbances in the microbiome-gut-brain axis with disease phenotypes in individuals with ASD will also addressed. Ruth Ann Luna, Texas Children’s Hospital Presented by: For Sponsorship Opportunities, email [email protected] For Programme Questions, email [email protected] February 10th-11th 2016 | San Diego, California, USA 17:30 Anxiety and Depression Increase in a Stepwise Manner in Parallel With Multiple FGIDs and Symptom Severity and Frequency Anxiety and depression occur frequently in patients with functional gastrointestinal disorders (FGIDs), but their precise prevalence is unknown. We addressed this issue in a large cohort of adult patients and determined the underlying factors. In total, 4,217 new outpatients attending 2 hospitals in Hamilton, Ontario, Canada completed questionnaires evaluating FGIDs and anxiety and depression (Hospital Anxiety and Depression scale). Chart review was performed in a random sample of 2,400 patients. Psychiatric comorbidity is common in patients referred to a secondary care center but is often unrecognized. The prevalence of both anxiety and depression is influenced by gender, presence of organic diseases, and FGIDs, and it increases with the number of coexistent FGIDs and frequency and severity of GI symptoms. Premysl Bercik, McMasters University 18:00 Infectious Diseases, Vaccine Development and CBER/FDA Regulatory Pathways Regulatory insight into: clinical practice in internal medicine and infectious diseases and conduct of phase 1 and 2 clinical trials as principal investigator. Infectious diseases, vaccine development and CBER/FDA regulatory pathways. Formulating vaccine development strategies and identifying programmatic obstacles. Working with public-private partnerships, national regulatory agencies, CDC and ACIP in addressing infectious disease vaccine issues and policies. Wellington Sun, FDA 18:30 Close of Conference Presented by: For Sponsorship Opportunities, email [email protected] For Programme Questions, email [email protected]