About

Dr. Michael C. Abt is an Assistant Professor in the Department of Microbiology at the Perelman School of Medicine, University of Pennsylvania. He joined the UPenn faculty in 2018. Prior to his faculty appointment, Dr. Abt conducted postdoctoral research at Memorial Sloan Kettering Cancer Center in the laboratory of Dr. Eric G. Pamer. He earned his PhD at the University of Pennsylvania, where he studied microbiota signaling that modulates antiviral immunity in the laboratories of Dr. David Artis and Dr. John Wherry. Dr. Abt's research focuses on the interactions between the gut microbiome and the immune system, particularly in the context of infectious diseases such as Clostridioides difficile infection. His work aims to understand how microbial and immune factors influence disease pathogenesis and host defense mechanisms.

Research topics

• Biology
• Immunology
• Microbiology
• Medicine
• Internal medicine
• Ecology
• Intensive care medicine
• Computational biology
• Bioinformatics

Selected publications

• Empowering global disease surveillance with CURED: a tool for rapid identification of unique genomic biomarkers

  mSystems · 2026-03-19

  articleOpen access

  ABSTRACT Rapid tracking of emerging pathogenic microorganisms is crucial for designing effective treatment, infection control, and prevention strategies. While whole-genome sequencing (WGS) offers the necessary granularity to track emerging clones, it remains prohibitively expensive at the scales needed to monitor with high resolution in real time. We present CURED (Classification Using Restriction Enzyme Diagnostics), which uses a training set of sequenced genomes to identify unique k-mers with restriction sites specific to a clonal lineage. CURED enables fast and inexpensive PCR-based diagnostic tests for surveillance or outbreak investigations with minimal use of WGS. Benchmarking against existing tools, CURED compares favorably and scales more efficiently than other k-mer search strategies. We validated and tested CURED in five distinct data sets: (i) previously identified biomarkers described for a methicillin-resistant Staphylococcus aureus (MRSA) clone in Rio de Janeiro, (ii) diagnostic alleles for different lineages in the USA300 MRSA clone, (ii) the extensively drug-resistant Acinetobacter baumannii Global Clone 1 lineage, (iv) toxigenic versus non-toxigenic Clostridioides difficile , and (v) circulating S. aureus clones in a neonatal intensive care unit (NICU). We implemented CURED as part of NICU infection prevention efforts and report the test’s speed, sensitivity, and specificity in a real-world setting. CURED is a scalable, multithreaded, memory-, and cost-efficient pipeline tailored for rapid clone detection and restriction site analysis. While particularly impactful for localized outbreak investigations and targeted surveillance, our preliminary work at the global scale suggests broader implementation is feasible. CURED is freely available at https://github.com/microbialARC/CURED . IMPORTANCE Timely and cost-effective detection of emerging microbial clones is essential for infection prevention and public health surveillance. While whole-genome sequencing remains the gold standard for tracking microbial evolution and transmission, its cost, infrastructure requirements, and turnaround time limit its scalability, especially in resource-limited settings. CURED addresses this gap by enabling the development of inexpensive, PCR-based diagnostic assays informed by genomic data, without requiring further sequencing. By identifying lineage-specific restriction sites through a scalable and memory-efficient k-mer pipeline, CURED enables the translation of genome-scale insights into actionable diagnostics. This tool supports broader implementation of genomic-informed diagnostics in both local and global pathogen surveillance efforts.

  PublisherDOI

• Generation and characterization of a novel MHC-II tetramer for tracking and characterization of toxin B-specific CD4 ⁺ T cell responses

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-19

  articleOpen accessSenior authorCorresponding

  Abstract The gastrointestinal pathogen Clostridioides difficile , is a major burden for health systems due to high rates of recurrence. C. difficile pathogenesis is mediated by two virulence factors, toxin A (TcdA) and Toxin B (TcdB). Antibodies specific for TcdA and TcdB are correlated with protection from symptomatic recurrence, however, the role for CD4 + T cells is poorly understood in part due to the lack of tools to study the toxin-specific CD4 + T cell response. Our group recently demonstrated the antibody and CD4 + T cell response to C. difficile toxins is impaired via the glucosyltransferase activity of the toxins; however, tools do not exist to study the protective capacity and the phenotype of toxin-specific CD4 + T cells. Therefore, we developed an MHC-II tetramer to identify TcdB-specific CD4 + T cells via flow cytometry. Herein, we identified an immunodominant epitope (TcdB 1961-1975 ) in the CROPs region of TcdB and optimized an MHC-II tetramer for use in tracking and phenotyping TcdB-specific CD4 + T cell responses following multiple different immunization strategies in mice. Utilizing the tetramer, TcdB-specific T follicular helper (Tfh) cells were detected following TcdB-CROPs mRNA-LNP vaccination validating the advantage of the tetramer. Furthermore, using a modular mRNA vector expressing the TcdB 1961 peptide covalently bound to the beta chain of MHC-II (MHC-IIβ) we were able to generate a robust population of TcdB-specific CD4 + T cells. These data outline the generation of new tools for the C. difficile field and lay the groundwork for future studies of toxin-specific CD4 + T cell responses.

  PublisherDOI

• Standard mouse diets lead to differences in severity in infectious and non-infectious colitis

  mBio · 2025-03-24 · 5 citations

  articleOpen accessSenior author

  ABSTRACT Clostridioides difficile infects the large intestine and can result in debilitating and potentially fatal colitis. The intestinal microbiota is a major factor influencing the severity of disease following infection. Factors like diet that shape microbiota composition and function may modulate C. difficile colitis. Here, we report that mice fed two distinct standard mouse chows (LabDiet 5010 and LabDiet 5053) exhibited significantly different susceptibility to severe C. difficile infection. Both diets are grain-based with comparable profiles of macro and micronutrient composition. Diet 5010-fed mice had severe morbidity and mortality compared to Diet 5053-fed mice despite no differences in C. difficile colonization or toxin production. Furthermore, Diet 5053 protected mice from toxin-induced epithelial damage. This protection was microbiota-dependent as germ-free mice or mice harboring a reduced diversity microbiota fed Diet 5053 were not protected from severe infection. However, cohousing with mice harboring a complex microbiota restored the protective capacity of Diet 5053 but not Diet 5010. Metabolomic profiling revealed distinct metabolic capacities between Diet 5010- and Diet 5053-fed intestinal microbiotas. Diet 5053-mediated protection extended beyond C. difficile infection as Diet 5053-fed mice displayed less severe dextran sodium sulfate-induced colitis than Diet 5010-fed mice, highlighting a potentially broader capacity for Diet 5053 to limit colitis. These findings demonstrate that standard diet formulations in combination with the host microbiota can drive variability in severity of infectious and non-infectious murine colitis systems, and that diet holds therapeutic potential to limit the severity of C. difficile infection through modulating the functional capacity of the microbiota. IMPORTANCE Diet is a major modulator of the microbiota and intestinal health. This report finds that two different standard mouse diets starkly alter the severity of colitis observed in a pathogen-mediated ( Clostridioides difficile ) and non-infectious (dextran sodium sulfate) mouse colitis experimental systems. These findings in part explain study-to-study variability using these mouse systems to study disease. Since the gut microbiota plays a key role in intestinal homeostasis, diet-derived modulation of the microbiota is a promising avenue to control disease driven by intestinal inflammation and may represent a potential intervention strategy for at-risk patients.

  PublisherDOI

• Sa1952: USING HUMAN COLONOIDS AS A 3D-MODEL TO STUDY THE EPITHELIAL RESPONSE OF CLOSTRIDIOIDES DIFFICILE INFECTION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

  Gastroenterology · 2025-05-01

  article
  PublisherDOI

• Therapeutic activation of IL-22-producing innate lymphoid cells enhances host defenses to Clostridioides difficile infection

  Cell Reports · 2025-03-26 · 4 citations

  articleOpen accessSenior author

  Clostridioides difficile causes debilitating colitis via secreted toxins that disrupt the intestinal barrier, and toxemia is associated with severe disease. Thus, therapies that fortify the intestinal barrier will reduce the severity of infection. Innate lymphoid cells (ILCs) are critical in the defense against acute C. difficile infection and represent a promising therapeutic target to limit disease. Here, we report that oral administration of the Toll-like receptor (TLR) 7 agonist R848 limits intestinal damage and protects mice from lethal C. difficile infection without impacting pathogen burden or altering the intestinal microbiome. R848 induced interleukin (IL)-22 secretion by ILCs, leading to STAT3 phosphorylation in the intestinal epithelium and increased stem cell proliferation. Genetic ablation of ILCs, IL-22, or epithelial-specific STAT3 abrogated R848-mediated protection. R848 reduced intestinal permeability following infection and limited systemic toxin dissemination. Combined, these data identify an immunostimulatory molecule that activates IL-22 production in ILCs to enhance host tissue defenses following C. difficile infection.

  PublisherDOI

• Clostridioides difficile toxin B inhibits antigen-specific adaptive immune responses through glucosyltransferase-dependent activity 3906

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description Clostridioides difficile colonizes the gastrointestinal tract and secretes two major virulence factors: toxin A (TcdA) and toxin B (TcdB). Protective immunity to C. difficile infection is limited as patients are susceptible to severe recurrent infections, often by the same strain as the primary infection. The adaptive immune responses to TcdA and TcdB following C. difficile infection remains incompletely defined. We determined that C. difficile-infected mice generate robust antibody responses to TcdA but not to TcdB. Furthermore, TcdA-responsive, but not TcdB-responsive, IL-17A producing-CD4+ T cells were detected following infection. To test if any toxin specific CD4+ T cells were present within the lamina propria, we developed a TcdB tetramer. Tetramer+ TcdB-specific CD4+ T cells were detected in the lamina propria; however, they were primarily FoxP3+ regulatory T cells. To determine whether failed immune responses to TcdB are driven by toxin activity, we utilized mutant strains of C. difficile that express enzymatically inactive (glucosyltransferase mutant [GTX]) TcdB. Infection with TcdB-GTX restored TcdB-specific antibody responses and lead to a lower regulatory T cell ratio among TcdB-specific CD4+ T cells. Taken together, these data demonstrate that the glucosyltransferase activity of TcdB hinders the adaptive immune response to TcdB. Inhibition of adaptive immunity by toxin activity may be a mechanism that underlies recurrent C. difficile infections in human patients. Funding Sources This work was funded by National Institutes of Health/National Institute of Allergy and Infectious Diseases Grants (R01AI158830 to M.C.A.; U19AI174998 to M.C.A., J.P.Z., M.G.A.; AI95755, BX002943, and AI174999 to D.B.L.). Topic Categories Mucosal and Regional Immunology (MUC)

  PublisherOA PDFDOI

• Role of IL10 signaling in the circadian control of host response to Influenza infection

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-10

  preprintOpen access

  Abstract We have previously demonstrated that the circadian clock regulates the host response to influenza A virus (IAV) infection, conferring a time-of-day-specific protection –infection at dawn resulted in a threefold increase in survival and reduced immunopathology compared to infection at dusk. While IL10 is well-known for its immunoregulatory function, its role in IAV remains unclear, with studies reporting both protective and detrimental effects. Given the diurnal rhythmicity of IL-10 receptor ( Il10ra ) expression in the lung, we investigated the contribution of IL-10 signaling to time-of-day-specific IAV protection. We found that blocking IL10 signaling abrogated the time of day protection, leading to increased immunopathology characterized by enhanced lymphocyte infiltration and global immune activation (transcriptomic analysis). Interestingly, while later, IL-10R blockade also eliminated the time-of-day difference in IAV outcomes, it improved the outcome of dusk-infected mice. Furthermore, natural killer (NK) cell depletion suppressed IL-10 levels in bronchoalveolar lavage, suggesting a role for NK cells in regulating IL-10 signaling. In conclusion, incorporating the circadian context has not only clarified the IL-10 role in IAV infection but also underscored the pivotal influence of circadian regulation on immune responses.

  PublisherOA PDFDOI

• Role of IL-10 signaling in the circadian control of host response to influenza infection

  Mucosal Immunology · 2025-11-21

  articleOpen access
  PublisherOA PDFDOI

• Clostridioides difficile toxin A and toxin B inhibit toxin-specific adaptive immune responses through glucosyltransferase-dependent activity

  Mucosal Immunology · 2025-08-18 · 2 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Advances in Understanding the Pathogenesis of Clostridioides difficile Infection

  Infectious Disease Clinics of North America · 2025-09-06

  reviewSenior author
  PublisherDOI

Recent grants

• Immune-Microbiota Interaction in defense against Clostridium difficile

  NIH · $498k · 2016–2020

• NIH Grant K99AI125786

  NIH · $223k · 2018

Frequent coauthors

• Eric G. Pamer

  University of Chicago

  19 shared

• David Artis

  Cornell University

  15 shared

• Joshua E. Denny

  National Human Genome Research Institute

  14 shared

• Marcel R.M. van den Brink

  Cornell University

  12 shared

• Jeffrey Maslanka

  University of Pennsylvania

  10 shared

• Matthew A. Firth

  University of Melbourne

  9 shared

• Timothy E. O’Sullivan

  University of California, Los Angeles

  9 shared

• Joseph C. Sun

  Memorial Sloan Kettering Cancer Center

  9 shared

Labs

• THE ABT LABPI

Education

• B.S., Biology

  Loyola University of Maryland

  2006

• Ph.D., Immunology

  University of Pennsylvania

  2012

Awards & honors

• NIH-NIDDK F31 fellowship (June 2024)