Scholars@Duke
John F. Rawls

John F. Rawls

James B. Duke Distinguished Professor of Molecular Genetics and Microbiology
Molecular Genetics and Microbiology
john.rawls@duke.edu
323A CARL Building, Box 3580, Durham, NC 27710
323A CARL Building Box 3580, 213 Research Drive, Durham, NC 27710

Selected Publications

Epithelial transcription factor Elf3 mediates host immune responses to microbiota and protects against aerocystitis in zebrafish.

Journal Article mBio · December 10, 2025 Animals defend against infections and other diseases by adaptively responding to the microbiota they encounter. These adaptations are driven by changes in gene expression programs; however, our understanding of the transcription factors regulating host res ... Full text Link to item Cite

Environmental Microbial Cues Alter Embryonic Development and Stress Responses in Vertebrates: Insights From the Zebrafish (Danio rerio) Model.

Journal Article Mol Ecol · December 2025 Host-microbiome interactions shape key physiological processes, including bioenergetics, neurodevelopment and xenobiotic metabolism, and strongly influence the ecological fitness of the host. However, our understanding of host-microbiome interactions is pr ... Full text Link to item Cite

Identification of intestinal enteroendocrine cell subtypes and their associated hormones in zebrafish.

Journal Article PLoS Biol · December 2025 Enteroendocrine cells (EECs) are rare sensory cells in the intestinal epithelium that coordinate digestive physiology by secreting a diverse repertoire of peptide hormones. These hormones are the main effectors of EEC function, and their characterization r ... Full text Link to item Cite

A gut sense for a microbial pattern regulates feeding.

Journal Article Nature · September 2025 To coexist with its resident microorganisms, the host must have a sense to adjust its behaviour in response to them. In the intestine, a sense for nutrients transduced to the brain through neuroepithelial circuits guides appetitive choices1-5. However, a s ... Full text Link to item Cite

Branched chain amino acid metabolism and microbiome in adolescents with obesity during weight loss therapy.

Journal Article medRxiv · June 9, 2025 BACKGROUND: Obesity and weight loss in adults have been associated with distinct metabolome and gut microbiome features, but the extent to which those associations apply to adolescent stages remain unclear. METHODS: The Pediatric Obesity Microbiome and Met ... Full text Link to item Cite

Role of the upper airway microbiota in respiratory virus and bacterial pathobiont dynamics in the first year of life.

Journal Article Nat Commun · June 4, 2025 The mechanisms by which respiratory viruses predispose to secondary bacterial infections remain poorly characterized. Using 2,409 nasopharyngeal swabs from 300 infants enrolled in a prospective cohort study in Botswana, we perform a detailed analysis of fa ... Full text Link to item Cite

Protein absorption in the zebrafish gut is regulated by interactions between lysosome rich enterocytes and the microbiome.

Journal Article Elife · March 13, 2025 Dietary protein absorption in neonatal mammals and fishes relies on the function of a specialized and conserved population of highly absorptive lysosome-rich enterocytes (LREs). The gut microbiome has been shown to enhance absorption of nutrients, such as ... Full text Link to item Cite

Early subclinical stages of the inflammatory bowel diseases: insights from human and animal studies.

Journal Article Am J Physiol Gastrointest Liver Physiol · January 1, 2025 The inflammatory bowel diseases (IBD) occur in genetically susceptible individuals that mount inappropriate immune responses to their microbiota leading to chronic intestinal inflammation. The natural history of IBD progression begins with early subclinica ... Full text Link to item Cite

Protein absorption in the zebrafish gut is regulated by interactions between lysosome rich enterocytes and the microbiome.

Journal Article bioRxiv · December 3, 2024 Dietary protein absorption in neonatal mammals and fishes relies on the function of a specialized and conserved population of highly absorptive lysosome rich enterocytes (LREs). The gut microbiome has been shown to enhance absorption of nutrients, such as ... Full text Link to item Cite

Zebrafish are resilient to the loss of major diacylglycerol acyltransferase enzymes.

Journal Article J Biol Chem · December 2024 In zebrafish, maternally deposited yolk is the source of nutrients for embryogenesis prior to digestive system maturation. Yolk nutrients are processed and secreted to the growing organism by an extra-embryonic tissue, the yolk syncytial layer (YSL). The e ... Full text Link to item Cite

A high-cholesterol zebrafish diet promotes hypercholesterolemia and fasting-associated liver steatosis.

Journal Article J Lipid Res · October 2024 Zebrafish are an ideal model organism to study lipid metabolism and to elucidate the molecular underpinnings of human lipid-associated disorders. Unlike murine models, to which various standardized high lipid diets such as a high-cholesterol diet (HCD) are ... Full text Link to item Cite

A zebrafish gene with sequence similarities to human uromodulin and GP2 displays extensive evolutionary diversification among teleost and confers resistance to bacterial infection.

Journal Article Heliyon · September 30, 2024 In the process of investigating synaptic changes happening to mutants lacking postsynaptic receptors in the neuromuscular junction, we focused on a hitherto uncharacterized zebrafish gene zgc153932 whose expression was increased in the RNAseq and droplet d ... Full text Link to item Cite

Pla2g12b drives expansion of triglyceride-rich lipoproteins.

Journal Article Nat Commun · March 7, 2024 Vertebrates transport hydrophobic triglycerides through the circulatory system by packaging them within amphipathic particles called Triglyceride-Rich Lipoproteins. Yet, it remains largely unknown how triglycerides are loaded onto these particles. Mutation ... Full text Link to item Cite

Pangenomic analysis identifies correlations between Akkermansia species and subspecies and human health outcomes.

Journal Article Microbiome Res Rep · 2024 Aim: Akkermansia are common members of the human gastrointestinal microbiota. The prevalence of these mucophilic bacteria, especially Akkermansia muciniphila (A. muciniphila), correlates with immunological and metabolic health. The genus Akkermansia in hum ... Full text Link to item Cite

Essential Amino Acid Metabolites as Chemical Mediators of Host-Microbe Interaction in the Gut.

Journal Article Annu Rev Microbiol · September 15, 2023 Amino acids are indispensable substrates for protein synthesis in all organisms and incorporated into diverse aspects of metabolic physiology and signaling. However, animals lack the ability to synthesize several of them and must acquire these essential am ... Full text Link to item Cite

Spontaneous episodic inflammation in the intestines of mice lacking HNF4A is driven by microbiota and associated with early life microbiota alterations.

Journal Article mBio · August 31, 2023 The inflammatory bowel diseases (IBD) occur in genetically susceptible individuals who mount inappropriate immune responses to their microbiota leading to chronic intestinal inflammation. Whereas IBD clinical presentation is well described, how interaction ... Full text Link to item Cite

Diversity of plant DNA in stool is linked to dietary quality, age, and household income.

Journal Article Proc Natl Acad Sci U S A · July 4, 2023 Eating a varied diet is a central tenet of good nutrition. Here, we develop a molecular tool to quantify human dietary plant diversity by applying DNA metabarcoding with the chloroplast trnL-P6 marker to 1,029 fecal samples from 324 participants across two ... Full text Link to item Cite

Conserved roles for Hnf4 family transcription factors in zebrafish development and intestinal function.

Journal Article Genetics · November 30, 2022 Transcription factors play important roles in the development of the intestinal epithelium and its ability to respond to endocrine, nutritional, and microbial signals. Hepatocyte nuclear factor 4 family nuclear receptors are liganded transcription factors ... Full text Link to item Cite

The intestine is a major contributor to circulating succinate in mice.

Journal Article FASEB J · October 2022 The tricarboxylic acid (TCA) cycle is the epicenter of cellular aerobic metabolism. TCA cycle intermediates facilitate energy production and provide anabolic precursors, but also function as intra- and extracellular metabolic signals regulating pleiotropic ... Full text Link to item Cite

Age-Related Changes in the Nasopharyngeal Microbiome Are Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Symptoms Among Children, Adolescents, and Young Adults.

Journal Article Clin Infect Dis · August 24, 2022 BACKGROUND: Children are less susceptible to SARS-CoV-2 infection and typically have milder illness courses than adults, but the factors underlying these age-associated differences are not well understood. The upper respiratory microbiome undergoes substan ... Full text Open Access Link to item Cite

Using zebrafish to understand reciprocal interactions between the nervous and immune systems and the microbial world.

Journal Article J Neuroinflammation · June 28, 2022 Animals rely heavily on their nervous and immune systems to perceive and survive within their environment. Despite the traditional view of the brain as an immunologically privileged organ, these two systems interact with major consequences. Furthermore, mi ... Full text Link to item Cite

Advanced Obesity Treatment Selection among Adolescents in a Pediatric Weight Management Program.

Journal Article Child Obes · June 2022 Background: Treatment options for adolescents with obesity are limited. Yet, therapies previously reserved for adults, such as medications and bariatric surgery, are increasingly available to adolescents in tertiary obesity treatment settings. We aimed to ... Full text Link to item Cite

Starvation causes changes in the intestinal transcriptome and microbiome that are reversed upon refeeding.

Journal Article BMC Genomics · March 22, 2022 BACKGROUND: The ability of animals and their microbiomes to adapt to starvation and then restore homeostasis after refeeding is fundamental to their continued survival and symbiosis. The intestine is the primary site of nutrient absorption and microbiome i ... Full text Link to item Cite

Non-diphtheriae Corynebacterium species are associated with decreased risk of pneumococcal colonization during infancy.

Journal Article ISME J · March 2022 Streptococcus pneumoniae (pneumococcus) is a leading cause of severe infections among children and adults. Interactions between commensal microbes in the upper respiratory tract and S. pneumoniae are poorly described. In this study, we sought to identify i ... Full text Link to item Cite

A Planar Culture Model of Human Absorptive Enterocytes Reveals Metformin Increases Fatty Acid Oxidation and Export.

Journal Article Cell Mol Gastroenterol Hepatol · 2022 BACKGROUND & AIMS: Fatty acid oxidation by absorptive enterocytes has been linked to the pathophysiology of type 2 diabetes, obesity, and dyslipidemia. Caco-2 and organoids have been used to study dietary lipid-handling processes including fatty acid oxida ... Full text Link to item Cite

Transcriptional Integration of Distinct Microbial and Nutritional Signals by the Small Intestinal Epithelium.

Journal Article Cell Mol Gastroenterol Hepatol · 2022 BACKGROUND & AIMS: The intestine constantly interprets and adapts to complex combinations of dietary and microbial stimuli. However, the transcriptional strategies by which the intestinal epithelium integrates these coincident sources of information remain ... Full text Link to item Cite

Microbial influences on gut development and gut-brain communication.

Journal Article Development · November 1, 2021 The developmental programs that build and sustain animal forms also encode the capacity to sense and adapt to the microbial world within which they evolved. This is abundantly apparent in the development of the digestive tract, which typically harbors the ... Full text Link to item Cite

Single-cell imaging of T cell immunotherapy responses in vivo.

Journal Article J Exp Med · October 4, 2021 T cell immunotherapies have revolutionized treatment for a subset of cancers. Yet, a major hurdle has been the lack of facile and predicative preclinical animal models that permit dynamic visualization of T cell immune responses at single-cell resolution i ... Full text Link to item Cite

Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine.

Journal Article Sci Adv · July 2021 Bile salt synthesis, secretion into the intestinal lumen, and resorption in the ileum occur in all vertebrate classes. In mammals, bile salt composition is determined by host and microbial enzymes, affecting signaling through the bile salt-binding transcri ... Full text Link to item Cite

Age-related changes in the upper respiratory microbiome are associated with SARS-CoV-2 susceptibility and illness severity.

Journal Article medRxiv · March 23, 2021 UNLABELLED: Children are less susceptible to SARS-CoV-2 and typically have milder illness courses than adults. We studied the nasopharyngeal microbiomes of 274 children, adolescents, and young adults with SARS-CoV-2 exposure using 16S rRNA gene sequencing. ... Full text Open Access Link to item Cite

The Pediatric Obesity Microbiome and Metabolism Study (POMMS): Methods, Baseline Data, and Early Insights.

Journal Article Obesity (Silver Spring) · March 2021 OBJECTIVE: The purpose of this study was to establish a biorepository of clinical, metabolomic, and microbiome samples from adolescents with obesity as they undergo lifestyle modification. METHODS: A total of 223 adolescents aged 10 to 18 years with BMI ≥9 ... Full text Open Access Link to item Cite

Acoustofluidic rotational tweezing enables high-speed contactless morphological phenotyping of zebrafish larvae.

Journal Article Nat Commun · February 18, 2021 Modern biomedical research and preclinical pharmaceutical development rely heavily on the phenotyping of small vertebrate models for various diseases prior to human testing. In this article, we demonstrate an acoustofluidic rotational tweezing platform tha ... Full text Link to item Cite

Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways.

Journal Article Cell Host Microbe · February 10, 2021 The intestinal epithelium senses nutritional and microbial stimuli using epithelial sensory enteroendocrine cells (EEC). EECs communicate nutritional information to the nervous system, but whether they also relay signals from intestinal microbes remains un ... Full text Link to item Cite

Transcriptional programmes underlying cellular identity and microbial responsiveness in the intestinal epithelium.

Journal Article Nat Rev Gastroenterol Hepatol · January 2021 The intestinal epithelium serves the unique and critical function of harvesting dietary nutrients, while simultaneously acting as a cellular barrier separating tissues from the luminal environment and gut microbial ecosystem. Two salient features of the in ... Full text Link to item Cite

Coordinating and Assisting Research at the SARS-CoV-2/Microbiome Nexus.

Journal Article mSystems · December 1, 2020 Although the COVID-19 pandemic is caused by a single virus, the rest of the human microbiome appears to be involved in the disease and could influence vaccine responses while offering opportunities for microbiome-directed therapeutics. The newly formed Mic ... Full text Link to item Cite

Conserved anti-inflammatory effects and sensing of butyrate in zebrafish.

Journal Article Gut Microbes · November 9, 2020 Short-chain fatty acids (SCFAs) are produced by microbial fermentation of dietary fiber in the gut. Butyrate is a particularly important SCFA with anti-inflammatory properties and is generally present at lower levels in inflammatory diseases associated wit ... Full text Link to item Cite

Single-cell imaging of human cancer xenografts using adult immunodeficient zebrafish.

Journal Article Nat Protoc · September 2020 Zebrafish are an ideal cell transplantation model. They are highly fecund, optically clear and an excellent platform for preclinical drug discovery studies. Traditionally, xenotransplantation has been carried out using larval zebrafish that have not yet de ... Full text Link to item Cite

Short-Chain Fatty Acid Production by Gut Microbiota from Children with Obesity Differs According to Prebiotic Choice and Bacterial Community Composition.

Journal Article mBio · August 11, 2020 Pediatric obesity remains a public health burden and continues to increase in prevalence. The gut microbiota plays a causal role in obesity and is a promising therapeutic target. Specifically, the microbial production of short-chain fatty acids (SCFA) from ... Full text Link to item Cite

Rationale and design of "Hearts & Parks": study protocol for a pragmatic randomized clinical trial of an integrated clinic-community intervention to treat pediatric obesity.

Journal Article BMC Pediatr · June 26, 2020 BACKGROUND: The prevalence of child and adolescent obesity and severe obesity continues to increase despite decades of policy and research aimed at prevention. Obesity strongly predicts cardiovascular and metabolic disease risk; both begin in childhood. Ch ... Full text Link to item Cite

RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro.

Journal Article Nat Commun · June 3, 2020 Fat distribution is an independent cardiometabolic risk factor. However, its molecular and cellular underpinnings remain obscure. Here we demonstrate that two independent GWAS signals at RSPO3, which are associated with increased body mass index-adjusted w ... Full text Link to item Cite

Abstract PR12: Dynamic single-cell imaging of human cancer growth and therapy responses following engraftment into immunodeficient zebrafish

Conference Cancer Research · June 1, 2020 AbstractCancer xenograft engraftment studies using immune-deficient mice are indispensable for preclinical drug discovery and are required for IND filings that lead to clinical trials. While immune-deficient ... Full text Cite

Feeling the Burn: Intestinal Epithelial Cells Modify Their Lipid Metabolism in Response to Bacterial Fermentation Products.

Journal Article Cell Host Microbe · March 11, 2020 Intestinal epithelial absorption of dietary lipids is a major determinant of animal energy balance and metabolic health. Recent studies uncovered significant roles for intestinal microbiota in this process, but underlying mechanisms remain unresolved. Araú ... Full text Link to item Cite

The emergence of microbiome centres.

Journal Article Nat Microbiol · January 2020 Full text Link to item Cite

The Pediatric Obesity Microbiome and Metabolism Study (POMMS): Methods, Baseline Data, and Early Insights

Journal Article · 2020 ABSTRACTObjective To establish a biorepository of clinical, metabolomic, and microbiome samples from adolescents with obesity as they undergo lifestyle modification. Methods We enrolled 223 adolescents aged 10-18 years with Body ... Full text Cite

Uncovering the history of intestinal host–microbiome interactions through vertebrate comparative genomics

Chapter · January 1, 2020 The genome of each organism encodes the information necessary for its development and physiology, and also provides a record of its natural history including its symbioses. A major challenge in symbiosis research is defining the signals exchanged between m ... Full text Cite

High fat diet induces microbiota-dependent silencing of enteroendocrine cells.

Journal Article Elife · December 3, 2019 Enteroendocrine cells (EECs) are specialized sensory cells in the intestinal epithelium that sense and transduce nutrient information. Consumption of dietary fat contributes to metabolic disorders, but EEC adaptations to high fat feeding were unknown. Here ... Full text Link to item Cite

Commensal Bacteria Regulate Gene Expression and Differentiation in Vertebrate Olfactory Systems Through Transcription Factor REST.

Journal Article Chem Senses · October 17, 2019 Sensory systems such as the olfactory system detect chemical stimuli and thereby determine the relationships between the animal and its surroundings. Olfaction is one of the most conserved and ancient sensory systems in vertebrates. The vertebrate olfactor ... Full text Link to item Cite

Lysosome-Rich Enterocytes Mediate Protein Absorption in the Vertebrate Gut.

Journal Article Dev Cell · October 7, 2019 The guts of neonatal mammals and stomachless fish have a limited capacity for luminal protein digestion, which allows oral acquisition of antibodies and antigens. However, how dietary protein is absorbed during critical developmental stages when the gut is ... Full text Link to item Cite

Epithelial delamination is protective during pharmaceutical-induced enteropathy.

Journal Article Proc Natl Acad Sci U S A · August 20, 2019 Intestinal epithelial cell (IEC) shedding is a fundamental response to intestinal damage, yet underlying mechanisms and functions have been difficult to define. Here we model chronic intestinal damage in zebrafish larvae using the nonsteroidal antiinflamma ... Full text Link to item Cite

Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish.

Journal Article Cell · June 13, 2019 Xenograft cell transplantation into immunodeficient mice has become the gold standard for assessing pre-clinical efficacy of cancer drugs, yet direct visualization of single-cell phenotypes is difficult. Here, we report an optically-clear prkdc-/-, il2rga- ... Full text Link to item Cite

Disrupted Maturation of the Microbiota and Metabolome among Extremely Preterm Infants with Postnatal Growth Failure.

Journal Article Sci Rep · June 3, 2019 Growth failure during infancy is a major global problem that has adverse effects on long-term health and neurodevelopment. Preterm infants are disproportionately affected by growth failure and its effects. Herein we found that extremely preterm infants wit ... Full text Link to item Cite

Intestinal Serum amyloid A suppresses systemic neutrophil activation and bactericidal activity in response to microbiota colonization.

Journal Article PLoS Pathog · March 2019 The intestinal microbiota influences the development and function of myeloid lineages such as neutrophils, but the underlying molecular mechanisms are unresolved. Using gnotobiotic zebrafish, we identified the immune effector Serum amyloid A (Saa) as one o ... Full text Link to item Cite

2017 NIH-wide workshop report on "The Human Microbiome: Emerging Themes at the Horizon of the 21st Century".

Journal Article Microbiome · February 26, 2019 The National Institutes of Health (NIH) organized a three-day human microbiome research workshop, August 16-18, 2017, to highlight the accomplishments of the 10-year Human Microbiome Project program, the outcomes of the investments made by the 21 NIH Insti ... Full text Link to item Cite

Commensal Microbiota Regulate Vertebrate Innate Immunity-Insights From the Zebrafish.

Journal Article Front Immunol · 2019 Microbial communities populate the mucosal surfaces of all animals. Metazoans have co-evolved with these microorganisms, forming symbioses that affect the molecular and cellular underpinnings of animal physiology. These microorganisms, collectively referre ... Full text Link to item Cite

An explant technique for high-resolution imaging and manipulation of mycobacterial granulomas.

Journal Article Nature methods · December 2018 A central and critical structure in tuberculosis, the mycobacterial granuloma consists of highly organized immune cells, including macrophages that drive granuloma formation through a characteristic epithelioid transformation. Difficulties in imaging withi ... Full text Cite

Pneumococcal Colonization and the Nasopharyngeal Microbiota of Children in Botswana.

Journal Article Pediatr Infect Dis J · November 2018 BACKGROUND: Nasopharyngeal colonization precedes infections caused by Streptococcus pneumoniae. A more detailed understanding of interactions between S. pneumoniae and the nasopharyngeal microbiota of children could inform strategies to prevent pneumococca ... Full text Link to item Cite

Deep phenotyping in zebrafish reveals genetic and diet-induced adiposity changes that may inform disease risk.

Journal Article J Lipid Res · August 2018 The regional distribution of adipose tissues is implicated in a wide range of diseases. For example, proportional increases in visceral adipose tissue increase the risk for insulin resistance, diabetes, and CVD. Zebrafish offer a tractable model system by ... Full text Link to item Cite

Zebrafish Transcription Factor ORFeome for Gene Discovery and Regulatory Network Elucidation.

Journal Article Zebrafish · April 2018 The completion of the zebrafish genome sequence and advances in miniaturization and multiplexing were essential to the creation of techniques such as RNA-seq, ChIP-seq, and high-throughput behavioral and chemical screens. Multiplexing was also instrumental ... Full text Link to item Cite

A High-Throughput Organoid Microinjection Platform to Study Gastrointestinal Microbiota and Luminal Physiology.

Journal Article Cell Mol Gastroenterol Hepatol · 2018 BACKGROUND & AIMS: The human gut microbiota is becoming increasingly recognized as a key factor in homeostasis and disease. The lack of physiologically relevant in vitro models to investigate host-microbe interactions is considered a substantial bottleneck ... Full text Link to item Cite

Intestinal Serum Amyloid A suppresses systemic neutrophil activation and bactericidal activity in response to microbiota colonization

Journal Article · 2018 The intestinal microbiota influence diverse aspects of host physiology, including the development and function of myeloid lineages. Numerous host and microbial factors are known to poise neutrophils and other granulocytes for response to pathogens and dang ... Full text Cite

Microbiome Variation

Chapter · 2018 Cite

Research Strategy

Chapter · 2018 Cite

Elucidating the role of plexin D1 in body fat distribution and susceptibility to metabolic disease using a zebrafish model system.

Journal Article Adipocyte · October 2, 2017 Non-communicable diseases (NCDs) such as cardiovascular disease, diabetes and cancer were responsible for 68% of all deaths worldwide in 2012. The regional distribution of lipid deposited within adipose tissue (AT) - so called body fat distribution (BFD) - ... Full text Link to item Cite

Microbial colonization is required for normal neurobehavioral development in zebrafish.

Journal Article Sci Rep · September 11, 2017 Changes in resident microbiota may have wide-ranging effects on human health. We investigated whether early life microbial disruption alters neurodevelopment and behavior in larval zebrafish. Conventionally colonized, axenic, and axenic larvae colonized at ... Full text Link to item Cite

The Nasopharyngeal Microbiota of Children With Respiratory Infections in Botswana.

Journal Article Pediatr Infect Dis J · September 2017 BACKGROUND: Nearly half of child pneumonia deaths occur in sub-Saharan Africa. Microbial communities in the nasopharynx are a reservoir for pneumonia pathogens and remain poorly described in African children. METHODS: Nasopharyngeal swabs were collected fr ... Full text Link to item Cite

The Intestinal Microbiome and Childhood Obesity

Journal Article Current Pediatrics Reports · September 1, 2017 Purpose of Review: Pediatric obesity has reached epidemic proportions worldwide. The community of microbes inhabiting the human intestine affects differential nutrient absorption, metabolism, and weight status. However, the majority of our knowledge is der ... Full text Cite

Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells.

Journal Article PLoS Biol · August 2017 The intestinal epithelium serves critical physiologic functions that are shared among all vertebrates. However, it is unknown how the transcriptional regulatory mechanisms underlying these functions have changed over the course of vertebrate evolution. We ... Full text Open Access Link to item Cite

Microbiota regulate intestinal epithelial gene expression by suppressing the transcription factor Hepatocyte nuclear factor 4 alpha.

Journal Article Genome Res · July 2017 Microbiota influence diverse aspects of intestinal physiology and disease in part by controlling tissue-specific transcription of host genes. However, host genomic mechanisms mediating microbial control of intestinal gene expression are poorly understood. ... Full text Link to item Cite

A classification system for zebrafish adipose tissues.

Journal Article Dis Model Mech · June 1, 2017 The zebrafish model system offers significant utility for in vivo imaging of adipose tissue (AT) dynamics and for screening to identify chemical and genetic modifiers of adiposity. In particular, AT can be quantified accurately in live zebrafish using fluo ... Full text Link to item Cite

Integrative Physiology: At the Crossroads of Nutrition, Microbiota, Animal Physiology, and Human Health.

Journal Article Cell Metab · March 7, 2017 Nutrition is paramount in shaping all aspects of animal biology. In addition, the influence of the intestinal microbiota on physiology is now widely recognized. Given that diet also shapes the intestinal microbiota, this raises the question of how the nutr ... Full text Link to item Cite

In vivo imaging and quantification of regional adiposity in zebrafish.

Journal Article Methods Cell Biol · 2017 Adipose tissues (ATs) are lipid-rich structures that supply and sequester energy-dense lipid in response to the energy status of an organism. As such, ATs provide an organism energetic insurance during periods of adverse physiological burden. ATs are depos ... Full text Link to item Cite

Best practices for germ-free derivation and gnotobiotic zebrafish husbandry.

Journal Article Methods Cell Biol · 2017 All animals are ecosystems with resident microbial communities, referred to as microbiota, which play profound roles in host development, physiology, and evolution. Enabled by new DNA sequencing technologies, there is a burgeoning interest in animal-microb ... Full text Link to item Cite

Genomic sequencing-based mutational enrichment analysis identifies motility genes in a genetically intractable gut microbe.

Journal Article Proc Natl Acad Sci U S A · December 6, 2016 A major roadblock to understanding how microbes in the gastrointestinal tract colonize and influence the physiology of their hosts is our inability to genetically manipulate new bacterial species and experimentally assess the function of their genes. We de ... Full text Link to item Cite

Contribution of neutral processes to the assembly of gut microbial communities in the zebrafish over host development.

Journal Article ISME J · March 2016 Despite their importance to host health and development, the communities of microorganisms associated with humans and other animals are characterized by a large degree of unexplained variation across individual hosts. The processes that drive such inter-in ... Full text Link to item Cite

The composition of the zebrafish intestinal microbial community varies across development.

Journal Article ISME J · March 2016 The assembly of resident microbial communities is an important event in animal development; however, the extent to which this process mirrors the developmental programs of host tissues is unknown. Here we surveyed the intestinal bacteria at key development ... Full text Link to item Cite

The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota.

Journal Article Hepatology · March 2016 UNLABELLED: Several animal studies have emphasized the role of gut microbiota in nonalcoholic fatty liver disease (NAFLD). However, data about gut dysbiosis in human NAFLD remain scarce in the literature, especially studies including the whole spectrum of ... Full text Link to item Cite

Got worms? Perinatal exposure to helminths prevents persistent immune sensitization and cognitive dysfunction induced by early-life infection.

Journal Article Brain Behav Immun · January 2016 The incidence of autoimmune and inflammatory diseases has risen dramatically in post-industrial societies. "Biome depletion" - loss of commensal microbial and multicellular organisms such as helminths (intestinal worms) that profoundly modulate the immune ... Full text Link to item Cite

Baby, It's Cold Outside: Host-Microbiota Relationships Drive Temperature Adaptations.

Journal Article Cell Host Microbe · December 9, 2015 When exposed to cold temperatures, mammals undergo remarkable physiological adaptations including thermogenesis, increased intake of dietary energy, and enhanced capacity for intestinal absorption. In a recent Cell paper, Chevalier, Stojanović, and colleag ... Full text Link to item Cite

Ontogenetic Differences in Dietary Fat Influence Microbiota Assembly in the Zebrafish Gut.

Journal Article mBio · September 29, 2015 UNLABELLED: Gut microbiota influence the development and physiology of their animal hosts, and these effects are determined in part by the composition of these microbial communities. Gut microbiota composition can be affected by introduction of microbes fr ... Full text Link to item Cite

CPAG: software for leveraging pleiotropy in GWAS to reveal similarity between human traits links plasma fatty acids and intestinal inflammation.

Journal Article Genome Biol · September 15, 2015 Meta-analyses of genome-wide association studies (GWAS) have demonstrated that the same genetic variants can be associated with multiple diseases and other complex traits. We present software called CPAG (Cross-Phenotype Analysis of GWAS) to look for simil ... Full text Open Access Link to item Cite

Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue.

Journal Article Proc Natl Acad Sci U S A · April 7, 2015 Genome-wide association studies have implicated PLEXIN D1 (PLXND1) in body fat distribution and type 2 diabetes. However, a role for PLXND1 in regional adiposity and insulin resistance is unknown. Here we use in vivo imaging and genetic analysis in zebrafi ... Full text Link to item Cite

Epigenetic control of intestinal barrier function and inflammation in zebrafish.

Journal Article Proc Natl Acad Sci U S A · March 3, 2015 The intestinal epithelium forms a barrier protecting the organism from microbes and other proinflammatory stimuli. The integrity of this barrier and the proper response to infection requires precise regulation of powerful immune homing signals such as tumo ... Full text Link to item Cite

Alteration of the rat cecal microbiome during colonization with the helminth Hymenolepis diminuta.

Journal Article Gut Microbes · 2015 The microbiome is now widely recognized as being important in health and disease, and makes up a substantial subset of the biome within the ecosystem of the vertebrate body. At the same time, multicellular, eukaryotic organisms such as helminths are being ... Full text Link to item Cite

Microbiota modulate transcription in the intestinal epithelium without remodeling the accessible chromatin landscape.

Journal Article Genome Res · September 2014 Microbiota regulate intestinal physiology by modifying host gene expression along the length of the intestine, but the underlying regulatory mechanisms remain unresolved. Transcriptional specificity occurs through interactions between transcription factors ... Full text Link to item Cite

Commensal microbiota stimulate systemic neutrophil migration through induction of serum amyloid A.

Journal Article Cell Microbiol · July 2014 Neutrophils serve critical roles in inflammatory responses to infection and injury, and mechanisms governing their activity represent attractive targets for controlling inflammation. The commensal microbiota is known to regulate the activity of neutrophils ... Full text Link to item Cite

Mucosal candidiasis elicits NF-κB activation, proinflammatory gene expression and localized neutrophilia in zebrafish.

Journal Article Dis Model Mech · September 2013 The epithelium performs a balancing act at the interface between an animal and its environment to enable both pathogen killing and tolerance of commensal microorganisms. Candida albicans is a clinically important human commensal that colonizes all human mu ... Full text Link to item Cite

Aquacultured rainbow trout (Oncorhynchus mykiss) possess a large core intestinal microbiota that is resistant to variation in diet and rearing density.

Journal Article Appl Environ Microbiol · August 2013 As global aquaculture fish production continues to expand, an improved understanding of how environmental factors interact in fish health and production is needed. Significant advances have been made toward economical alternatives to costly fishmeal-based ... Full text Link to item Cite

Oesophageal and sternohyal muscle fibres are novel Pax3-dependent migratory somite derivatives essential for ingestion.

Journal Article Development · July 2013 Striated muscles that enable mouth opening and swallowing during feeding are essential for efficient energy acquisition, and are likely to have played a fundamental role in the success of early jawed vertebrates. The developmental origins and genetic requi ... Full text Link to item Cite

Carbon monoxide and heme oxygenase-1 prevent intestinal inflammation in mice by promoting bacterial clearance.

Journal Article Gastroenterology · April 2013 BACKGROUND & AIMS: Heme oxygenase-1 (HO-1) and its metabolic by-product, carbon monoxide (CO), protect against intestinal inflammation in experimental models of colitis, but little is known about their intestinal immune mechanisms. We investigated the inte ... Full text Link to item Cite

Dwarfism and increased adiposity in the gh1 mutant zebrafish vizzini.

Journal Article Endocrinology · April 2013 Somatic growth and adipogenesis are closely associated with the development of obesity in humans. In this study, we identify a zebrafish mutant, vizzini, that exhibits both a severe defect in somatic growth and increased accumulation of adipose tissue. Pos ... Full text Link to item Cite

Animals in a bacterial world, a new imperative for the life sciences.

Journal Article Proc Natl Acad Sci U S A · February 26, 2013 In the last two decades, the widespread application of genetic and genomic approaches has revealed a bacterial world astonishing in its ubiquity and diversity. This review examines how a growing knowledge of the vast range of animal-bacterial interactions, ... Full text Link to item Cite

Microgavage of zebrafish larvae.

Journal Article J Vis Exp · February 20, 2013 The zebrafish has emerged as a powerful model organism for studying intestinal development(1-5), physiology(6-11), disease(12-16), and host-microbe interactions(17-25). Experimental approaches for studying intestinal biology often require the in vivo intro ... Full text Link to item Cite

Glafenine-induced intestinal injury in zebrafish is ameliorated by μ-opioid signaling via enhancement of Atf6-dependent cellular stress responses.

Journal Article Dis Model Mech · January 2013 Beside their analgesic properties, opiates exert beneficial effects on the intestinal wound healing response. In this study, we investigated the role of μ-opioid receptor (MOR) signaling on the unfolded protein response (UPR) using a novel zebrafish model ... Full text Link to item Cite

Increased rectal microbial richness is associated with the presence of colorectal adenomas in humans.

Journal Article ISME J · October 2012 Differences in the composition of the gut microbial community have been associated with diseases such as obesity, Crohn's disease, ulcerative colitis and colorectal cancer (CRC). We used 454 titanium pyrosequencing of the V1-V2 region of the 16S rRNA gene ... Full text Link to item Cite

Microbiota regulate intestinal absorption and metabolism of fatty acids in the zebrafish.

Journal Article Cell Host Microbe · September 13, 2012 Regulation of intestinal dietary fat absorption is critical to maintaining energy balance. While intestinal microbiota clearly impact the host's energy balance, their role in intestinal absorption and extraintestinal metabolism of dietary fat is less clear ... Full text Link to item Cite

Intestinal microbiota composition in fishes is influenced by host ecology and environment.

Journal Article Mol Ecol · July 2012 The digestive tracts of vertebrates are colonized by complex assemblages of micro-organisms, collectively called the gut microbiota. Recent studies have revealed important contributions of gut microbiota to vertebrate health and disease, stimulating intens ... Full text Link to item Cite

Intronic cis-regulatory modules mediate tissue-specific and microbial control of angptl4/fiaf transcription.

Journal Article PLoS Genet · 2012 The intestinal microbiota enhances dietary energy harvest leading to increased fat storage in adipose tissues. This effect is caused in part by the microbial suppression of intestinal epithelial expression of a circulating inhibitor of lipoprotein lipase c ... Full text Link to item Cite

Evidence for a core gut microbiota in the zebrafish.

Journal Article ISME J · October 2011 Experimental analysis of gut microbial communities and their interactions with vertebrate hosts is conducted predominantly in domesticated animals that have been maintained in laboratory facilities for many generations. These animal models are useful for s ... Full text Link to item Cite

Microbial colonization induces dynamic temporal and spatial patterns of NF-κB activation in the zebrafish digestive tract.

Journal Article Gastroenterology · July 2011 BACKGROUND & AIMS: The nuclear factor κ-light-chain enhancer of activated B cells (NF-κB) transcription factor pathway is activated in response to diverse microbial stimuli to regulate expression of genes involved in immune responses and tissue homeostasis ... Full text Link to item Cite

In vivo analysis of white adipose tissue in zebrafish.

Journal Article Methods Cell Biol · 2011 White adipose tissue (WAT) is the major site of energy storage in bony vertebrates, and also serves central roles in the endocrine regulation of energy balance. The cellular and molecular mechanisms underlying WAT development and physiology are not well un ... Full text Link to item Cite

Study of host-microbe interactions in zebrafish.

Journal Article Methods Cell Biol · 2011 All animals are ecosystems, home to diverse microbial populations. Animal-associated microbes play important roles in the normal development and physiology of their hosts, but can also be agents of infectious disease. Traditionally, mice have been used to ... Full text Link to item Cite

Host-microbe interactions in the developing zebrafish.

Journal Article Curr Opin Immunol · February 2010 The amenability of the zebrafish to in vivo imaging and genetic analysis has fueled expanded use of this vertebrate model to investigate the molecular and cellular foundations of host-microbe relationships. Study of microbial encounters in zebrafish hosts ... Full text Link to item Cite

Tuberculous granuloma induction via interaction of a bacterial secreted protein with host epithelium.

Journal Article Science · January 22, 2010 Granulomas, organized aggregates of immune cells, are a hallmark of tuberculosis and have traditionally been thought to restrict mycobacterial growth. However, analysis of Mycobacterium marinum in zebrafish has shown that the early granuloma facilitates my ... Full text Link to item Cite

Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas.

Journal Article Gut Microbes · 2010 The human large bowel is colonized by complex and diverse bacterial communities. However, the relationship between commensal bowel bacteria and adenomas (colorectal cancer precursors) is unclear. This study aimed to characterize adherent bacteria in normal ... Full text Link to item Cite

Ontogeny and nutritional control of adipogenesis in zebrafish (Danio rerio).

Journal Article J Lipid Res · August 2009 The global obesity epidemic demands an improved understanding of the developmental and environmental factors regulating fat storage. Adipocytes serve as major sites of fat storage and as regulators of energy balance and inflammation. The optical transparen ... Full text Link to item Cite

Patterns and scales in gastrointestinal microbial ecology.

Journal Article Gastroenterology · May 2009 The body surfaces of humans and other animals are colonized at birth by microorganisms. The majority of microbial residents on the human body exist within gastrointestinal (GI) tract communities, where they contribute to many aspects of host biology and pa ... Full text Link to item Cite

Methods for generating and colonizing gnotobiotic zebrafish.

Journal Article Nat Protoc · 2008 Vertebrates are colonized at birth by complex and dynamic communities of microorganisms that can contribute significantly to host health and disease. The ability to raise animals in the absence of microorganisms has been a powerful tool for elucidating the ... Full text Link to item Cite

Enteric infection and inflammation alter gut microbial ecology.

Journal Article Cell Host Microbe · August 16, 2007 The complex microbial community residing within the intestine plays important roles in host defense. However, the impact of enteric infection and inflammation on this resident community has not been fully explored. In this issue of Cell Host & Microbe, Lup ... Full text Link to item Cite

In vivo imaging and genetic analysis link bacterial motility and symbiosis in the zebrafish gut.

Journal Article Proc Natl Acad Sci U S A · May 1, 2007 Complex microbial communities reside within the intestines of humans and other vertebrates. Remarkably little is known about how these microbial consortia are established in various locations within the gut, how members of these consortia behave within the ... Full text Link to item Cite

Reciprocal gut microbiota transplants from zebrafish and mice to germ-free recipients reveal host habitat selection.

Journal Article Cell · October 20, 2006 The gut microbiotas of zebrafish and mice share six bacterial divisions, although the specific bacteria within these divisions differ. To test how factors specific to host gut habitat shape microbial community structure, we performed reciprocal transplanta ... Full text Link to item Cite

Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota.

Journal Article Proc Natl Acad Sci U S A · March 30, 2004 Animals have developed the means for supporting complex and dynamic consortia of microorganisms during their life cycle. A transcendent view of vertebrate biology therefore requires an understanding of the contributions of these indigenous microbial commun ... Full text Link to item Cite

Temporal and molecular separation of the kit receptor tyrosine kinase's roles in zebrafish melanocyte migration and survival.

Journal Article Dev Biol · October 1, 2003 The Kit receptor tyrosine kinase is required by vertebrate melanocytes for their migration and survival. The relationship between these developmental roles of Kit, however, remains poorly understood. Here, we use two genetic approaches to demonstrate that ... Full text Link to item Cite

Coupled mutagenesis screens and genetic mapping in zebrafish.

Journal Article Genetics · March 2003 Forward genetic analysis is one of the principal advantages of the zebrafish model system. However, managing zebrafish mutant lines derived from mutagenesis screens and mapping the corresponding mutations and integrating them into the larger collection of ... Full text Link to item Cite

How the zebrafish gets its stripes.

Journal Article Dev Biol · December 15, 2001 The study of vertebrate pigment patterns is a classic and enduring field of developmental biology. Knowledge of pigment pattern development comes from a variety of systems, including avians, mouse, and more recently, the zebrafish (Danio rerio). Recent ana ... Full text Link to item Cite

Requirements for the kit receptor tyrosine kinase during regeneration of zebrafish fin melanocytes.

Journal Article Development · June 2001 Embryonic neural crest-derived melanocytes and their precursors express the kit receptor tyrosine kinase and require its function for their migration and survival. However, mutations in kit also cause deficits in melanocytes that make up adult pigment patt ... Full text Link to item Cite

Mutational analysis of endothelin receptor b1 (rose) during neural crest and pigment pattern development in the zebrafish Danio rerio.

Journal Article Dev Biol · November 15, 2000 Pigment patterns of fishes are a tractable system for studying the genetic and cellular bases for postembryonic phenotypes. In the zebrafish Danio rerio, neural crest-derived pigment cells generate different pigment patterns during different phases of the ... Full text Link to item Cite

Zebrafish kit mutation reveals primary and secondary regulation of melanocyte development during fin stripe regeneration.

Journal Article Development · September 2000 Fin regeneration in adult zebrafish is accompanied by re-establishment of the pigment stripes. To understand the mechanisms underlying fin stripe regeneration and regulation of normal melanocyte stripe morphology, we investigated the origins of melanocytes ... Full text Link to item Cite

Zebrafish sparse corresponds to an orthologue of c-kit and is required for the morphogenesis of a subpopulation of melanocytes, but is not essential for hematopoiesis or primordial germ cell development.

Journal Article Development · August 1999 The relative roles of the Kit receptor in promoting the migration and survival of amniote melanocytes are unresolved. We show that, in the zebrafish, Danio rerio, the pigment pattern mutation sparse corresponds to an orthologue of c-kit. This finding allow ... Full text Link to item Cite

SCAR, a WASP-related protein, isolated as a suppressor of receptor defects in late Dictyostelium development.

Journal Article J Cell Biol · September 7, 1998 G protein-coupled receptors trigger the reorganization of the actin cytoskeleton in many cell types, but the steps in this signal transduction cascade are poorly understood. During Dictyostelium development, extracellular cAMP functions as a chemoattractan ... Full text Link to item Cite