About

Casey Theriot is a professor whose research spans molecular microbiology, protein biochemistry, microbial ecology, and bacterial pathogenesis. His multidisciplinary training has fostered innovative approaches to understanding bacterial mechanisms of pathogenesis. His early research included studying Desulfovibrio in primate intestinal tracts exposed to elemental mercury, and working at the CDC on antimicrobial resistance monitoring and clinical enteric pathogen isolates. During his graduate studies at North Carolina State University, he focused on characterizing metalloproteases in Archaeal organisms and engineered proteins from Pyrococcus species for detoxification of nerve agents, applying biochemistry and protein structure expertise. His current research investigates the gastrointestinal microbiota's role in Clostridium difficile pathogenesis, particularly how antibiotics disrupt gut microbiota and influence resistance to C. difficile colonization. His work integrates high-throughput analysis of the microbiome, metabolome, and host immune responses in animal models and human samples, aiming to elucidate the complex interactions among the microbiota, pathogens, and the host to inform public health strategies.

Research topics

• Microbiology
• Biology
• Genetics
• Biochemistry
• Computer Science
• Ecology
• Virology
• Business
• Food science
• Chemistry
• Immunology

Selected publications

• Bile acid dependent attenuation of toxin mediated disease is independent of colonization resistance against <i>C. difficile</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-12

  articleOpen accessSenior authorCorresponding

  ABSTRACT Clostridioides difficile infection (CDI) is a severe antibiotic associated disease and a major cause of morbidity and mortality worldwide. CDI is thought to arise from the loss of protective gut microbes that mediate functions such as secondary bile acid metabolism and nutrient competition, yet the relative contributions of these mechanisms remain unclear. To determine how these processes influence C. difficile growth, virulence, and disease, we performed in vitro and in vivo experiments using two Clostridia strains previously associated with colonization resistance against C. difficile . Neither organism prevented colonization or growth through nutrient competition alone. In contrast, secondary bile acid metabolism significantly reduced toxin-mediated disease in vivo in a strain dependent manner. These findings demonstrate that secondary bile acid modulation is an important component of CDI prevention independent of nutrient competition and suggest that attenuating virulence, in addition to limiting colonization, may represent a key strategy for next-generation CDI therapeutics.

  PublisherOA PDFDOI

• Dietary protein source alters gut microbiota composition and function

  The ISME Journal · 2025-01-01 · 35 citations

  articleOpen access

  The source of protein in a person's diet affects their total life expectancy. However, the mechanisms by which dietary protein sources differentially impact human health and life expectancy are poorly understood. Dietary choices impact the composition and function of the intestinal microbiota that ultimately modulate host health. This raises the possibility that health outcomes based on dietary protein sources might be driven by interactions between dietary protein and the gut microbiota. In this study, we determined the effects of seven different sources of dietary protein on the gut microbiota of mice using an integrated metagenomics-metaproteomics approach. The protein abundances measured by metaproteomics can provide microbial species abundances, and evidence for the molecular phenotype of microbiota members because measured proteins indicate the metabolic and physiological processes used by a microbial community. We showed that dietary protein source significantly altered the species composition and overall function of the gut microbiota. Different dietary protein sources led to changes in the abundance of microbial proteins involved in the degradation of amino acids and the degradation of glycosylations conjugated to dietary protein. In particular, brown rice and egg white protein increased the abundance of amino acid degrading enzymes. Egg white protein increased the abundance of bacteria and proteins usually associated with the degradation of the intestinal mucus barrier. These results show that dietary protein sources can change the gut microbiota's metabolism, which could have major implications in the context of gut microbiota mediated diseases.

  PublisherOA PDFDOI

• Experimental glycopeptide antibiotic EVG7 prevents recurrent Clostridioides difficile infection by sparing members of the Lachnospiraceae family

  Nature Communications · 2025-10-10 · 1 citations

  articleOpen access

  Oral vancomycin has a long history as the first-line treatment for Clostridioides difficile infection (CDI), but its use is associated with high relapse rates. Antibiotics that more selectively target C. difficile while sparing protective commensal gut bacteria, have the potential to prevent recurrent CDI (rCDI). Here, we investigate the experimental glycopeptide antibiotic, EVG7, in the context of rCDI. In vitro susceptibility assays reveal that clinical C. difficile isolates are up to 16-times more sensitive to EVG7 (MIC = 0.063-0.25 mg/L) compared to vancomycin (MIC = 0.5-2 mg/L). In a validated mouse model of rCDI in male mice, low dose oral EVG7 (0.04 mg/mL in drinking water) more effectively treats primary CDI and prevents recurrence, outperforming a 10-fold higher dose of vancomycin. Subsequent microbiome analysis and in vitro susceptibility testing reveal that EVG7 preserves Lachnospiraceae, a family of commensal bacteria associated with protection against C. difficile colonization.

  PublisherOA PDFDOI

• Successful Fecal Microbiota Transplants in Post-antibiotic Treated Recurrent Clostridioides difficile Patients Induce Acylcarnitine and Sphingolipid Lipidomic Shifts

  Research Square · 2025-11-03 · 1 citations

  preprintOpen accessSenior author
  PublisherOA PDFDOI

• Assessing contamination in DNA extraction kits commonly used for microbiome research

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-23

  preprintOpen access

  Abstract Sequencing-based measurements are now routinely used to investigate the microbial world, however, contamination by DNA outside the intended sample remains a problem. Contaminants obscure the true microbial signal and can lead to misleading scientific interpretations. Much work has been done to address the effects of these contaminants including best practices as outlined in Eisenhofer et al . and Fierer et al . Yet, even with best practices in place, the current literature consensus is that contaminants remain impactful, at least in low biomass environments (5, 7, 11, 13, 16). One well-known source of contaminants are those found within DNA extraction kits, as was shown clearly in the pioneering work of Salter et al. 2012 and Karstens et al. 2019 . However, given the rapid evolution of DNA sequencing methods, it would be worthwhile to revisit the issue of contaminants in contemporary DNA extraction kits (the “kitome”). Here we provide an updated characterization of the ‘kitomes’ of DNA extraction kits commonly used for microbiome research. Importance Microbial contamination in commonly used DNA extraction kits has not been recently assessed. Here we evaluate the contamination in DNA extraction kits commonly used in microbiome studies over the past several years, and provide actionable guidance on appropriate DNA extraction kits for low biomass microbiome measurements.

  PublisherOA PDFDOI

• Dietary protein from different sources escapes host digestion and is differentially modified by gut microbiota

  Food & Function · 2025-01-01 · 8 citations

  articleOpen access

  Protein is an essential macronutrient and variations in its source and quantity have been shown to impact long-term health outcomes. Differential health impacts of dietary proteins from various sources are likely driven by differences in their digestibility by the host and subsequent availability to the intestinal microbiota. However, our current understanding regarding the fate of dietary proteins from different sources in the gut, specifically how component proteins within these sources interact with the host and the gut microbiota, is limited. To determine which dietary proteins are efficiently digested by the host, and which proteins escape host digestion and are used by the gut microbiota, we used high-resolution mass spectrometry to quantify proteins that constitute different dietary protein sources before and after digestion in germ-free and conventionally raised mice. We detected proteins from all sources in fecal samples of both germ-free and conventional mice suggesting that even protein sources with high digestive efficiency make it to the colon where they can serve as metabolic substrate for gut microbiota. Additionally, we found that specific component proteins of dietary protein sources were degraded to a greater extent in the presence of the microbiota. We found that specific proteins with functions that could potentially impact host health and physiology were differentially enriched in germ-free or conventionally raised mice. These findings reveal large differences in the fate of dietary protein from various sources in the gut which could explain some of their differential health impacts.

  PublisherOA PDFDOI

• <i>Clostridioides difficile</i> Toxins Alter Host Metabolic Pathway and Bile Acid Homeostasis Gene Expression In Colonic Epithelium

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-21

  preprintOpen accessSenior authorCorresponding

  Abstract A major risk factor for acquiring Clostridioides difficile is antibiotic usage that disrupts a healthy microbial gut community facilitating establishment of infection. Once established, C. difficile secretes endotoxins (TcdA and TcdB) that are internalized into host colonic epithelial cells where they disrupt gut barrier function and induce hyper inflammation resulting in severe diarrhea and possibly leading to death. We employed three different platforms to explore gene expression of cells in the gut when exposed to C. difficile or its toxins, TcdA and TcdB. An antibiotic treated mouse model of C. difficile infection (CDI) was used to identify differential gene expression with a NanoString Technologies mouse inflammatory gene panel consisting of 770 genes including a subset of bile acid (BA) homeostasis and nuclear receptor genes. In the cecal tissue of mice with CDI, significant down expression was observed for genes involved in PPAR signaling, cholesterol and glucose metabolism, while a significant increase in expression was observed for IL-17 related inflammatory genes. Similarly, Caco-2 cell culture and primary human colonocytes (hCE) exposed to toxins for 24 hours showed altered expression in several PPAR regulated and cholesterol metabolic genes similar to those found in mice. These cell culture experiments also revealed significant alterations in gene expression of the FXR BA regulatory pathway. Together these data suggest that exposure to C. difficile and its toxins may alter host cholesterol metabolic processes, including BA transport and synthesis.

  PublisherOA PDFDOI

• Differential modulation of post-antibiotic colonization resistance to <i>Clostridioides difficile</i> by two probiotic <i>Lactobacillus</i> strains

  mBio · 2025-07-21 · 4 citations

  articleOpen accessSenior author

  ABSTRACT Probiotics are often consumed after antibiotic treatment to prevent antibiotic-associated diarrheal disease, most commonly caused by Clostridioides difficile . However, the impact of probiotic bacteria on the post-antibiotic gut microbiota is undetermined and often overlooked. Here, we examined the effect of a single dose of probiotic Lactobacillus acidophilus NCFM and Lactobacillus gasseri Lg-36 on colonization resistance against C. difficile in an antibiotic-treated mouse model. We found that L. acidophilus administration increased C. difficile infection and impaired the restoration of colonization resistance. In contrast, L. gasseri decreased C. difficile and promoted the return of colonization resistance, presumably through a putative bacteriocin inhibiting C. difficile . However, L. gasseri transiently colonizes the mouse gut, and its administration impacts colonization resistance after it is no longer detectable. We analyzed the gut microbiota of mice and found that members of the understudied Muribaculaceae family were enriched after L. gasseri administration and associated with colonization resistance. Using Muribaculum intestinale and Duncaniella muris , we determined that elevated growth of these species can restrict C. difficile growth in vitro , suggesting that these bacteria may play a role in establishing colonization resistance in vivo . These findings highlight the potential pitfalls of specific probiotic strains taken after antibiotic treatment and support the need for further investigations of their influence on the gut microbiota post-antibiotic. Additionally, this work supports the role of the Muribaculaceae as beneficial gut commensals that can contribute to colonization resistance against C. difficile and illustrates the need to decipher community interactions in complex microbial consortia. IMPORTANCE Probiotic research has overwhelmingly generalized the safety of select strains perceived as beneficial, while most studies are based on individual strains to substantiate particular functional attributes. In contrast, Clostridioides difficile studies document how this complex pathogen interacts with diverse members of the gut microbiota to cause diarrheal disease. Despite their purported ability to inhibit pathogens and modulate the gut microbiota, probiotics have been used to treat C. difficile infections with little success. In this study, we examine how common probiotics can impact the recovery of the gut microbiota after antibiotics by measuring colonization resistance against C. difficile in a mouse model. We show that Lactobacillus acidophilus enhances C. difficile infection, while Lactobacillus gasseri promotes colonization resistance potentially through its expression of bacteriocins and an enrichment of Muribaculaceae . This work highlights the complexity of probiotic interactions with pathogens and the indigenous microbiota and further supports that the overlooked Muribaculaceae are capable of inhibiting C. difficile .

  PublisherDOI

• Structure-guided design of a synthetic bile acid that inhibits Clostridioides difficile TcdB toxin

  Nature Microbiology · 2025-11-18 · 1 citations

  article
  PublisherDOI

• <i>Clostridioides difficile</i> toxins alter host metabolic pathway and bile acid homeostasis gene expression in colonic epithelium

  Infection and Immunity · 2025-06-30

  articleOpen accessSenior author

  ABSTRACT A major risk factor for acquiring Clostridioides difficile is antibiotic usage that disrupts a healthy microbial gut community, facilitating the establishment of infection. Once established, C. difficile secretes exotoxins (TcdA and TcdB) that are internalized into host colonic epithelial cells where they disrupt gut barrier function and induce hyperinflammation resulting in severe diarrhea and possibly leading to death. We employed three different platforms to explore gene expression of cells in the gut when exposed to C. difficile or its toxins, TcdA and TcdB. An antibiotic-treated mouse model of Clostridioides difficile infection (CDI) was used to identify differential gene expression with a NanoString Technologies mouse inflammatory gene panel consisting of 770 genes, including a subset of bile acid (BA) homeostasis and nuclear receptor genes. In the cecal tissue of mice with CDI, reduced expression was observed for genes involved in peroxisome proliferator-activated receptor (PPAR) signaling and cholesterol and glucose metabolism, while a significant increase in expression was observed for IL-17 related inflammatory genes. Similarly, Caco-2 cell culture and primary human colonic epithelial cells (hCE) exposed to toxins for 24 h showed altered expression in several PPAR-regulated and cholesterol metabolic genes similar to those found in mice. These cell culture experiments also revealed significant alterations in gene expression of the Farnesoid X receptor BA regulatory pathway. Together, these data suggest that exposure to C. difficile and its toxins may alter host cholesterol metabolic processes, including BA transport and synthesis.

  PublisherDOI

Recent grants

• Shifts in the Gastrointestinal Metabolome During Clostridium difficile Infection

  NIH · $371k · 2013–2017

• Targeted bacterial restoration of colonization resistance against C. difficile

  NIH · $1.6M · 2016–2022

Frequent coauthors

• Vincent B. Young

  University of Michigan–Ann Arbor

  29 shared

• Jun Lu

  Shandong Provincial Hospital

  16 shared

• Rajani Thanissery

  North Carolina State University

  15 shared

• Yawei Zhang

  Fudan University

  13 shared

• Ingrid L. Bergin

  University of Michigan–Ann Arbor

  13 shared

• Alissa J. Rivera

  North Carolina State University

  13 shared

• Matthew H. Foley

  North Carolina State University

  13 shared

• Stephanie A. Montgomery

  University of North Carolina at Chapel Hill

  13 shared

Labs

• Theriot LaboratoryPI

Education

• Ph.D., Animal Science

  North Carolina State University

  2006

• M.S., Animal Science

  North Carolina State University

  2002

• B.S., Animal Science

  Louisiana State University

  2000