About

Christopher A. Gaulke is an Assistant Professor in the Department of Pathobiology at the University of Illinois College of Veterinary Medicine. He earned his PhD from the University of California, Davis, and his BS from Central Washington University. His research focuses on understanding how the microbiome influences health by examining the mechanisms through which it modulates the effects of environmental exposures on host physiology. His lab conducts studies that utilize high-throughput screens, statistical modeling, and advanced molecular techniques to identify environmental factors that disturb the microbiome's taxonomic, genetic, and metabolic composition. By integrating host physiological and immunological measures, his work aims to detect interactions between microbiome operation and host health, with goals including identifying biomarkers of exposure, elucidating microbial bioremediation pathways, and engineering microbial consortia to mitigate exposure impacts and promote health. He is also affiliated with the Personalized Nutrition Initiative at the Carl R. Woese Institute for Genomic Biology and the National Center for Supercomputing Applications.

Research topics

• Biology
• Computational biology
• Microbiology
• Computer Science
• Immunology
• Bioinformatics
• Chromatography
• Genetics
• Internal medicine
• Medicine
• Ecology
• Cell biology
• Biochemistry
• Data science
• Chemistry
• Pharmacology

Selected publications

• Sex-stratified Gut Microbiome Disruption is Associated with Altered Hepatic Gene Expression during Acute Azoxystrobin Exposure

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-18

  articleOpen accessSenior authorCorresponding

  Abstract Azoxystrobin is a widely used fungicide that has been associated with to reproductive, neurological, and developmental defects. This chemical also disrupts gut microbial communities; however, if these perturbations contribute to the harms associated with exposure to azoxystrobin, this remains unclear. In this study, we investigated the effects of acute exposure to a series of concentrations (5–500 mg/kg) of azoxystrobin on the host and gut microbiota in zebrafish. Fecal amplicon and shotgun metagenomic sequencing was integrated with liver gene expression to quantify associations between microbiome disruption azoxystrobin toxicity in the host. Azoxystrobin exposure resulted in significant alteration in microbiome composition and functional potential in a dose- and sex-dependent manner. Microbial communities in exposed animals exhibited an increased abundance of xenobiotic metabolism pathways and decreased bacterial motility and lipopolysaccharide biosynthesis pathway metabolism. At the host level, histopathology identified increased biliary proliferation, most evident in medium- and high-dose fish. We also observed hepatic transcriptional changes consistent with a stress response, including altered redox-associated genes and reduced expression of lipid and small-molecule metabolic genes, with sex-stratified differences. Importantly, alterations in host transcriptional programming correlated with the compositional changes in exposed microbiota. Together, these results suggest concurrent impacts of azoxystrobin on gut microbiota and the liver implicate the microbiome as a potential contributor to changes in liver gene expression during exposure. Importance Widespread fungicide use contaminates ecosystems worldwide, but the biological pathways underlying their effects on humans and other animals are not well understood. Using zebrafish ( Danio rerio ), we found that short-term exposure to the fungicide azoxystrobin was associated with changes in the gut microbiome, liver gene activity, and liver changes. Exposure produced dose- and sex-dependent shifts in microbial communities, including changes in predicted microbial functions involved in chemical metabolism, bacterial motility and defense. Compositional changes in the microbiome correlated with gene-expression changes consistent with stress and altered metabolism in exposed fish, suggesting that exposure induced disruption may contribute to exposure impact to the host. These results highlight a potential role for the microbiome in mediation of the impacts of azoxystrobin on host physiology. As such microbial based interventions could be a viable strategy to mitigate exposure impacts on health.

  PublisherDOI

• Cooked Broccoli Alters Cecal Microbiota and Impacts Microbial Metabolism of Glucoraphanin in Lean and Obese Mice

  Molecular Nutrition & Food Research · 2025-02-17 · 2 citations

  articleOpen access

  SCOPE: Brassica vegetables contain unique compounds known as glucosinolates (GSLs), which, when hydrolyzed by plant or microbial myrosinase, form bioactive isothiocyanates (ITCs) that offer health benefits to the host. The present study evaluated the impact of cooked broccoli (broccoli myrosinase inactivated) consumption on cecal microbial metabolism of glucoraphanin (GRP) in lean and obese mice and characterized the changes in cecal microbiota following broccoli-containing diets. METHODS AND RESULTS: Twenty lean and 20 diet-induced obese (DIO) mice were randomized to consume control or cooked broccoli supplemented diets for 7 days. Cooked broccoli consumption increased ex vivo microbial GRP hydrolysis by cecal contents collected from lean and obese mice, led to increased production of sulforaphane (SF), sulforaphane-cysteine (SF-CYS), total ITC, and colonic NAD(P)H: Quinone Oxidoreductase (NQO1) activity. Further investigation revealed increased abundance of health-promoting gut microbiota, including Lachnospiraceae NK4A136 group and Dubosiella newyorkensis, following broccoli-containing diets. The Peptococcaseae family, the Blautia genus, and an amplicon sequence variation (ASV) from the Oscillospiraceae family exhibited negative correlation with total ITC production. CONCLUSION: These finding suggest that cooked broccoli consumption enhances microbial GRP hydrolysis to produce more bioactive ITCs and inform future strategies toward altering microbial GSL metabolism to promote gut health in both lean and obese individuals.

  PublisherOA PDFDOI

• Comparative analysis of the Streptococcus pneumoniae competence development in vitro versus in vivo during pneumonia-derived sepsis

  Frontiers in Microbiology · 2025-01-28 · 4 citations

  articleOpen access

  Introduction The Streptococcus pneumoniae (pneumococcus) competence regulon is well-known for regulating genetic transformation but is also important for virulence. Some pneumococcal strains can enter a transient competent state for genetic transformation in an optimized competence-inducing medium when the threshold level of the peptide pheromone competence stimulating peptide is attained; upregulating the expression of three distinct phases of “early”, “late” and “delayed” competence genes. Recently, we discovered that pneumococcus can naturally enter a prolonged competent state during acute pneumonia in mice. However, mechanisms driving competence development during host infection are rarely examined, and a direct comparison between in vitro and in vivo competence induction has not been performed. Methods We conducted a comparative gene expression analysis of pneumococcal competence development in vitro versus in vivo during pneumonia-derived sepsis in mice. We examined existing RNA-Seq data and performed validation using RNA obtained from an independent replicate experiment. Results and discussion Our analysis revealed both similarities and differences in the expression of “early”, “late”, and “delayed” competence between in vitro versus during pneumonia-derived sepsis. Our results may reveal new aspects of pneumococcal competence biology.

  PublisherOA PDFDOI

• Maternal vaccination partially protects piglets against influenza A virus associated alteration of the microbiome and hippocampal gene expression

  Veterinary Microbiology · 2025-05-08 · 1 citations

  articleOpen access1st authorCorresponding

  Influenza A virus (IAV) causes respiratory disease with systemic complications in a variety of avian and mammalian hosts, including humans and pigs. Infection with IAV in newborns can be particularly damaging as viral infection is known to disrupt the rapid developmental processes that occur during this period. Maternal IAV vaccination can reduce the risk of IAV infection in infants, but it is unknown whether passive transfer of anti-IAV antibodies protect against the downstream complications of infection. In this study, we evaluated the impact of maternal vaccination on the gut and nasal microbiota development and hippocampal transcriptome in neonatal piglets infected with influenza A virus. Sows were either vaccinated with an experimental influenza A vaccine at 70- and 90-days gestation, or mock-vaccinated with PBS. Neonatal piglets born from vaccinated and unvaccinated sows were challenged with a pathogenic IAV isolate or mock-challenged with PBS at 6 days post-farrowing and euthanized five days post challenge. Vaccination significantly reduced lung lesions and infectious viral load in piglets. Nasal and gut microbial community development was also partially protected from viral disruption as indicated by increased deviation from pre-challenge timepoints compared to animals challenged with the virus from unvaccinated mothers. Bulk RNA sequencing of hippocampal tissue identified 1146 differentially expressed genes (FDR < 0.05) between groups. IAV-infected piglets from vaccinated sows showed increases in genes related to viral immune responses, while IAV-infected piglets from unvaccinated sows showed increases in genes related to neurogenesis and decreases in genes related to vascular development. Many of these differentially regulated genes were strongly correlated with microbial community abundances, indicating that the microbiota may contribute to IAV outcomes. Notably, nasal microbial abundances intricately connected with hippocampal gene expression patterns, suggesting a strong nasal microbiome-brain communication axis in early development. Together, our results indicate that maternal vaccination partially protects neonatal piglets against influenza virus infection and mitigates the potential long-term impacts of IAV infection on the microbiome and cognition.

  PublisherDOI

• Influence of Housing, Sex, and Sampling Location on Taxonomy and Function of Adult Zebrafish Microbiomes

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-08

  preprintOpen accessSenior authorCorresponding

  ) has emerged as an important animal model for the study of host-microbiome interactions. However, information on how variation in experimental parameters contribute to microbiome structure and function in adult zebrafish is limited which complicates experimental design, interpretation of results, and may reduce reproducibility. Here we quantified the impact of two potential sources of microbiome variation - housing strategy and sampling location - on microbial diversity of adult zebrafish using 16S rRNA amplicon sequencing. Our findings indicate that housing strategy significantly impacts gut microbiome diversity in adult fish with the highest similarity between individuals co-housed on recirculating water systems. Microbiome acclimation after housing transfer took between 14- and 21-days. Significant variation in microbiome composition was also observed across sampling sites. As in humans, fecal and intestinal microbial communities were similar and varied by sex, however each body site sampled possessed a small site-specific microbial community signature. Consistently, imputed function of these communities showed that gene family diversity is also predicted to vary by body site particularly between gut and non-gut locations. Together our work demonstrates that housing, sex, and sampling strategy all significantly impact microbial community composition and highlight the need for community wide discussions on best practices and reporting standards for adult zebrafish microbiome studies.

  PublisherOA PDFDOI

• Long Term Culture of Germ-Free Zebrafish Using Gamma-Irradiated Feeds

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-09

  preprintOpen accessSenior authorCorresponding

  model that is increasingly used to resolve causality in host-microbiota interactions. However, reliance on live diets and autoclaved diets limits the use of gnotobiotic zebrafish to early life stages where body systems and microbial communities are incompletely developed. As a result, many important host-microbiota interactions may be unable to be studied in this model system. Here, we tested a simple method for long-term husbandry of gnotobiotic zebrafish using gamma-irradiated chow diets and evaluated effects on growth, gene expression, and microbial community composition. In conventionally reared animals, gamma-irradiated diets did not affect growth or survival and only modestly impacted microbial community composition and diversity. In contrast, germ-free zebrafish maintained on sterile irradiated diets for 55 days post-fertilization were smaller, weighed less, and exhibited aberrant gene expression profiles relative to controls. These genes were enriched for pathways related to immune response, xenobiotic metabolism, organ development, liver function, and lipid metabolism, with many expression patterns linked to the abundance of specific microbial taxa. Together, these findings establish a practical protocol for long-term maintenance of gnotobiotic zebrafish and extend the utility of this model to study microbiome-dependent effects on host physiology and development beyond early larval stages of life.IMPORTANCEWhile the gnotobiotic zebrafish have been a powerful model for interrogation of host-microbiota interactions, their use has been limited to early life stages due to complications of long-term husbandry. To address this limitation, we developed a simple protocol that enables rearing germ-free zebrafish well beyond larval stages. Germ-free fish exhibit physiological and developmental defects that mirror those described in mammalian counterparts supporting a conserved role for microbiota in vertebrate development and physiology. Our protocol provides a method to investigate microbial influences on adaptive immunity, metabolism, and chronic disease processes in zebrafish not possible with current methodologies. Given the rapid and simple methods for gnotobiotic derivation and the large number of transgenic animal lines available for zebrafish, we anticipate this model will accelerate mechanistic discovery of microbial impacts on host health.

  PublisherOA PDFDOI

• Portal bile acid composition and microbiota along the <i>murine</i> intestinal tract exhibit sex differences in physiology

  Gut Microbes · 2025-08-04 · 7 citations

  articleOpen accessCorresponding

  Microbes in the intestine transform bile acids during transit, altering their functional and signaling capacities before recirculation via the portal vein. Sex differences in the gut microbiota have been noted, but their consequence on bile acid composition is unclear. Here, we investigated the composition and functional potential of microbes in the small and large intestines together with portal and systemic bile acid levels. Female and male mice exhibit distinct microbial diversity throughout the length of the intestine, leading to dimorphism in genes related to bile acid transformation. Of note, genes linked to bacterial oxidative properties were abundant in males, and consistently, we found 3X higher oxo-bile acids in portal circulation in males than females. Conversely, conjugated primary bile acids were 1.8X more abundant in the portal bile acid pool of female mice. Oxidized and deconjugated bile acids were absent in germ-free mice consistent with microbe-mediated bile acid transformation. More importantly, gnotobiotic mice do not show sex differences in portal bile acids. Taken together, we demonstrate that sex differences in gut microbiota with subsequent changes in microbially transformed bile acid levels contribute to distinct sex-specific bile acid pools within the enterohepatic loop.

  PublisherDOI

• Gut microbiota metabolically mediate intestinal helminth infection in Zebrafish

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-07-27

  preprintOpen access

  Intestinal helminth parasite (IHP) infection induces alterations in the composition of microbial communities across vertebrates, although how gut microbiota may facilitate or hinder parasite infection remains poorly defined. In this work we utilized a zebrafish model to investigate the relationship between gut microbiota, gut metabolites, and IHP infection. We found that extreme disparity in zebrafish parasite infection burden is linked to the composition of the gut microbiome, and that changes in the gut microbiome are associated with variation in a class of endogenously-produced signaling compounds, N-acylethanolamines, that are known to be involved in parasite infection. Using a statistical mediation analysis, we uncovered a set of gut microbes whose relative abundance explains the association between gut metabolites and infection outcomes. Experimental investigation of one of the compounds in this analysis reveals salicylaldehyde, which is putatively produced by the gut microbe Pelomonas, as a potent anthelmintic with activity against Pseudocapillaria tomentosa egg hatching, both in vitro and in vivo. Collectively, our findings underscore the importance of the gut microbiome as a mediating agent in parasitic infection and highlights specific gut metabolites as tools for the advancement of novel therapeutic interventions against IHP infection.

  PublisherOA PDFDOI

• Portal bile acids and microbiota along the murine intestinal tract exhibit sex differences in physiology

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-07-16

  preprintOpen accessCorresponding

  Microbes in the intestine transform bile acids during transit, altering their functional and signaling capacities before absorption into the portal vein. Sex differences in the gut microbiota have been noted, but their consequence on bile acid composition is unclear. Here, we investigated the composition and imputed functional potential of microbes in the small and large intestine together with portal and systemic bile acids. Female and male mice exhibit distinct microbial diversity throughout the length of the intestine leading to dimorphism in genes related to bile acid transformation. Subsequently, we found that the total portal bile acid concentrations were doubled in female mice compared to males. Conversely, oxo-bile acids that are rare in systemic circulation represented almost 30 percent of the portal pool in the male mice. Oxo- and deconjugated- bile acids were absent in germ-free mice consistent with microbe-mediated bile acid transformation. More importantly, gnotobiotic mice do not show sex differences in portal bile acids. Taken together, we demonstrate that sex differences in gut microbiota cause dimorphism in bile acid levels within the enterohepatic loop.

  PublisherOA PDFDOI

• Gut microbiota metabolically mediate intestinal helminth infection in zebrafish

  mSystems · 2024-08-27 · 14 citations

  articleOpen access

  ABSTRACT Intestinal helminth parasite (IHP) infection induces alterations in the composition of microbial communities across vertebrates, although how gut microbiota may facilitate or hinder parasite infection remains poorly defined. In this work, we utilized a zebrafish model to investigate the relationship between gut microbiota, gut metabolites, and IHP infection. We found that extreme disparity in zebrafish parasite infection burden is linked to the composition of the gut microbiome and that changes in the gut microbiome are associated with variation in a class of endogenously produced signaling compounds, N-acylethanolamines, that are known to be involved in parasite infection. Using a statistical mediation analysis, we uncovered a set of gut microbes whose relative abundance explains the association between gut metabolites and infection outcomes. Experimental investigation of one of the compounds in this analysis reveals salicylaldehyde, which is putatively produced by the gut microbe Pelomonas , as a potent anthelmintic with activity against Pseudocapillaria tomentosa egg hatching, both in vitro and in vivo . Collectively, our findings underscore the importance of the gut microbiome as a mediating agent in parasitic infection and highlight specific gut metabolites as tools for the advancement of novel therapeutic interventions against IHP infection. IMPORTANCE Intestinal helminth parasites (IHPs) impact human health globally and interfere with animal health and agricultural productivity. While anthelmintics are critical to controlling parasite infections, their efficacy is increasingly compromised by drug resistance. Recent investigations suggest the gut microbiome might mediate helminth infection dynamics. So, identifying how gut microbes interact with parasites could yield new therapeutic targets for infection prevention and management. We conducted a study using a zebrafish model of parasitic infection to identify routes by which gut microbes might impact helminth infection outcomes. Our research linked the gut microbiome to both parasite infection and to metabolites in the gut to understand how microbes could alter parasite infection. We identified a metabolite in the gut, salicylaldehyde, that is putatively produced by a gut microbe and that inhibits parasitic egg growth. Our results also point to a class of compounds, N-acyl-ethanolamines, which are affected by changes in the gut microbiome and are linked to parasite infection. Collectively, our results indicate the gut microbiome may be a source of novel anthelmintics that can be harnessed to control IHPs.

  PublisherDOI

Frequent coauthors

• Thomas J. Sharpton

  Oregon State University

  40 shared

• Michael L. Kent

  California Northstate University

  15 shared

• Virginia Watral

  Oregon State University

  13 shared

• Sean Spagnoli

  Oregon State University

  9 shared

• Satya Dandekar

  University of California, Davis

  9 shared

• Maurício A. Martins

  8 shared

• Sumathi Sankaran‐Walters

  University of California, Davis

  8 shared

• Lauren A. Hirao

  8 shared

Labs

• Gaulke LabPI