About

Dr. Christopher Lehmann is an Assistant Professor of Medicine in the Department of Medicine at The University of Chicago. His research is driven by the urgent need to address the global crisis of antibiotic resistance. Since the discovery of antibiotics in the early to mid-20th century, bacteria have rapidly evolved mechanisms to resist their effects, leading to a rise in infections and deaths caused by drug-resistant pathogens. Dr. Lehmann’s work focuses on an alternative strategy informed by a growing understanding of the human microbiome. He develops approaches to restore and protect the beneficial components of the microbiome, which play a critical role in maintaining health by competing with and suppressing harmful microbes. His research aims to prevent infections, reduce reliance on traditional antibiotics, and provide new avenues in the fight against antibiotic-resistant disease.

Research topics

• Medicine
• Bioinformatics
• Internal medicine
• Microbiology
• Biology
• Immunology
• Gastroenterology
• Intensive care medicine
• Physiology
• Virology
• Endocrinology
• Biochemistry

Selected publications

• P-1783. Blood Metagenomic Next-Generation Sequencing and its Impact on Antimicrobial Management

  Open Forum Infectious Diseases · 2026-01-01

  articleOpen access

  Abstract Background Blood metagenomic next-generation sequencing, commercially known as the Karius test (Karius, Redwood City, CA), is a diagnostic tool that can aid clinicians in uncovering pathogens that might otherwise be challenging to diagnose by standard microbiological techniques. However, due to its cost, use in clinical practice is limited. Published studies have found conflicting impact on clinical management, thus the appropriate clinical scenarios for Karius testing require further investigation. We evaluated the indications for Karius testing and impact on antimicrobial management to develop evidence-based recommendations for test ordering at our institution. Methods In a retrospective chart review, we examined 135 Karius tests ordered between 2023-2024 at an academic medical center for pediatric and adult patients. Patient demographics and diagnoses associated with the test were collected. All microbiology and antimicrobial data before and after test results were examined. The clinical outcome of 30-day mortality was evaluated. Results A total of 135 patients were tested, demographics shown in Table 1. There were 143 diagnoses listed as the indication for test ordering (Figure 1). There were 69 positive tests and 21% were concordant with microbiology cultures while 8% were discordant. There were 19 results (14%) that changed management. The diagnoses most likely to have management change in response to testing are shown in Figure 2A-B. The types of antimicrobial changes are listed in Figure 2C. A total of 142 organisms were identified, 91 bacterial, 32 viral and 19 fungal. Figure 2D depicts management changes occurring in bacterial (52%) and fungal organisms (42%). Within 30 days of the test, 20% patients died (Figure 3). Conclusion In summary, we retrospectively assessed the indications and impact of Karius testing for patients at our institution. Karius tests changed antimicrobial management most often with liver abscess, culture-negative endocarditis, and pneumonia. While fungi represented a minority of organisms, they resulted in most of the antimicrobial changes. High rates of 30-day mortality were observed. Our data suggest Karius is most impactful with specific diagnoses, fungal pathogens, and non-critically ill patients. Disclosures All Authors: No reported disclosures

  PublisherDOI

• P-1569. Microbiome Derived Stool Metabolites Predict E. faecium Expansion in Hospitalized Patients

  Open Forum Infectious Diseases · 2026-01-01

  articleOpen accessSenior author

  Abstract Background Vancomycin resistant Enterococcus faecium (VRE) poses a distinct threat to hospitalized patients.(CDC, 2022) Expansion of VRE within the gut microbiome is closely linked with invasive infections in multiple hosts.(Lehmann et al., 2024; Taur et al., 2012) Stool microbial metabolite measurement offers a new diagnostic avenue to rapidly identify VRE colonization. (Lehmann et al., 2024) We developed a machine learning model using stool metabolite measurements to predict E. faecium expansion in patients.Table 1.Patient Characteristics.Demographic information of the patients whose samples were utilized to train and test this model.Figure 1.Overall performance of the Elastic Net Model.A. Receiver operator characteristic plot showing true positive vs false positive rates. This demonstrates an area under the curve of 0.919. B. Table displaying a variety of model performance metrics. Notably, this model demonstrates a high F1 score of 0.935 as well as positive and negative predictive values of 0.915 and 0.804 respectively. C. Confusion Matrix of model performance on unseen test data. Methods Using qualitative stool metabolite concentrations as measured by targeted GC and LC-MS analysis paired with microbiota composition obtained via shotgun metagenomic sequencing, we generated, tuned, and evaluated an elastic net-based machine learning model to predict stool expansion of E. faecium over 30% relative abundance.(Kuhn, 2008) Collinearity and multicollinearity analysis of the metabolites was performed using Spearman’s Rank-Order method, and Variance Inflation Factors respectively. Following hyperparametric tuning of this model, test data was used to evaluate the model’s performance. The selected classification cutoff for the model maximized the F1 score based on precision and recall.Figure 2.Collinearity Assessment of Stool Metabolites.A. Top 10 pairwise Spearman Correlations are listed with both respective metabolites and the absolute value of their correlation. B. All metabolites that demonstrate high multicollinearity (VIF>10) are shown with their respective variance inflation factor. Results 2738 stool samples from 1504 patients were included from 6 observational clinical studies on liver disease, liver transplant, heart transplant, critical care, internal medicine, and leukemia patients.(Dela Cruz et al., 2023; Lehmann et al., 2024; Odenwald et al., 2023; Stutz et al., 2022) (Table 1) The model predicted E. faecium expansion with an accuracy was 0.894, sensitivity of 0.949, precision of 0.919 and AUC of 0.917. (Figure 1.) Conclusion This work provides a proof of concept that stool metabolites can identify pathogen expansion in the gut. The approach could aid in early diagnosis leading to better outcomes. It could also identify key inhibitory metabolites as future therapeutic candidates. Future work will identify the metabolites with highest predictive value and apply this method to other gut pathogens such as Klebsiella pneumonia. Disclosures Bhakti Patel, MD, CHEST: Board review course director|Merck: Wrote medical chapters

  PublisherDOI

• P-960. Improving Resident Education on the Inpatient Infectious Disease Consult Service

  Open Forum Infectious Diseases · 2025-01-29

  articleOpen access

  Abstract Background Education in infectious disease (ID) is a critical part of an internal medicine curriculum. As the infectious disease consult service is typically high volume and busy, residents and other trainees were often not receiving adequate training in less common infectious conditions or didactic training in common conditions that may be relevant for their future practice or internal medicine board exams. Our Quality Improvement project sought to improve training for residents and medical students through the integration of high-yield lecture services given on the Adult ID consult service.Figure 1:Pre/Post Test Results of Internal Medicine Residents These are the reported correct responses, in terms of percentage of residents who responded correctly to the case-based multiple choice question, to a pre and post test of six specific high-yield topics in Infectious Diseases. Methods During the academic year of 2022-2023, for the Adult ID Consult Service, a series of high-yield lectures were given three times a week from a set of 10 potential lecture topics, as chosen by the volunteer faculty or ID fellow lecturer. Following our first Plan-Do-Study-Act cycle evaluation in July 2023, the lectures were standardized to a fixed rotating schedule of the 6 highest-yield topics. There was distributed a survey with a pre-test before the rotation, and a follow-up survey and post-test following the rotation. Post-intervention Interest in Career in ID among Internal Medicine Residents 15.4% (n=2) of internal medicine residents responded yes they would, and 38.5% (n=5) responded somewhat more likely, to consider a career in Infectious Diseases (ID) following the rotation. Results 44 Internal Medicine Residents took the initial Adult ID survey and pretest, and 13 people took the post-rotation evaluation survey and post-test. 100% of participants felt the rotation fully or somewhat helped prepare for the Adult ID section of Internal Medicine boards. 92.3% (n=12) felt the majority of cases on rotation to be interesting. 15.4% (n=2) responded yes and 38.5% (n=5) responded somewhat more likely to consider ID as a career. 100% (n=13) of post-test participants responded with strongly agree (n=7, 53.8%) or agree (n=6, 46.2%) on enjoying the Adult ID rotation. Additionally, scores on the post-test improved from the pre-test for most residents, along with an improvement in Internal Medicine in-training exam scores from 2021 to 2023. Conclusion A didactic series with a set lesson plan that is delivered in a low-stress way can be helpful for engaging learners, enhance the educational experience of the learner, help supplement preparation for internal medicine board exams, and prepare the learner for their future practice. Additionally, as there is a growing need for infectious diseases fellows, this may improve recruitment efforts. Disclosures Aniruddha Hazra, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|ViiV Healthcare: Advisor/Consultant

  PublisherOA PDFDOI

• Uncovering bacterial pseudaminylation with pan-specific antibody tools

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-13 · 1 citations

  preprintOpen access

  Abstract Pseudaminic acids (Pse) are a family of carbohydrates found within bacterial lipopolysaccharides, capsular polysaccharides and glycoproteins that are critical for the virulence of human pathogens. However, a dearth of effective tools for detecting and enriching Pse has restricted study to only the most abundant Pse-containing glycoconjugates. Here, we devise a synthesis of α- and β-O-pseudaminylated glycopeptides to generate ‘pan-specific’ monoclonal antibodies (mAbs) that recognise α- and β-configured Pse and its C8 epimer (8ePse) presented within glycans or directly linked to polypeptide backbones. Structural characterisation reveals the molecular basis of Pse recognition across a range of diverse chemical contexts. Using these mAbs, we establish a glycoproteomic platform to provide unprecedented depth in mapping the Pse glycome of Helicobacter pylori , Campylobacter jejuni , and Acinetobacter baumannii strains. Finally, we demonstrate that the mAbs recognise diverse capsule types in multidrug-resistant Acinetobacter baumannii and enhance phagocytosis to eliminate infections in mice.

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• Fecal Butyrate and Deoxycholic Acid Concentrations Correlate With Mortality in Patients With Liver Disease

  Gastro Hep Advances · 2025-01-01 · 5 citations

  articleOpen access

  Background and Aims: The intestinal microbiome produces metabolites, including short chain fatty acids (SCFAs) and secondary bile acids (BAs), that impact host physiology. Loss of intestinal microbiome diversity is associated with cirrhosis progression, but the impact of microbiome-associated metabolites on liver disease remains largely undefined. We aimed to correlate fecal metabolite concentrations with the severity and progression of liver disease. Methods: In this cross-sectional study, fecal samples from patients hospitalized with liver disease were analyzed by shotgun metagenomic sequencing to determine microbiome compositions and targeted mass spectrometry to quantify SCFAs and BAs. Random survival forest and logistic regression models identified clinical, metagenomic, and metabolomic features associated with rehospitalization and survival. Results: . Conclusion: Mass spectrometry rapidly identifies patients with low fecal butyrate and DCA concentrations who are at increased risk of 30-day mortality. These findings set the stage for clinical trials of microbiome reconstitution with butyrate and DCA-producing bacterial species.

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• 434. Reduced Gut Microbiome Diversity and Compositional Characteristics are Associated with Postoperative Infection in Heart Transplant Recipients

  Open Forum Infectious Diseases · 2025-01-29

  articleOpen access

  Abstract Background The human microbiome has been linked to important clinical outcomes, including postoperative infection. Loss of diversity has been associated with drug resistant organism colonization, infection, immune defenses, epithelial barrier integrity, and death. The microbiome’s role in postoperative infection among heart transplant (HT) recipients remains poorly understood.Table 1Clinical CharacteristicsTable 1 Clinical Characteristics: Characteristics noted by number and percent or mean and Standard Deviation where appropriate. Abbreviations: ICM – Ischemic Cardiomyopathy; NICM – Non-ischemic cardiomyopathy; CKD – Chronic Kidney Disease; COPD – Chronic Obstructive Pulmonary Disease. Methods Stool microbiomes for 121 HT recipients were determined by metagenomic sequencing. Infections occurring in the first 100 days following transplant were aggregated. Infection was defined as the presence of a compatible clinical syndrome and a positive test result via culture, PCR, serology, or imaging. To determine if infection risk was related to stool microbiome composition, samples at the time of transplant were shotgun sequenced and taxonomy was determined using MetaPhLan 4. Alpha diversity was measured by inverse Simpson, beta diversity was measure by Bray-Curtis dissimilarity.Table 2:Infection Microbiology and Diagnoses Results Average age at HT was 53.6 years and 73% were male, and the cause of heart failure in 71% was nonischemic cardiomyopathy. 194 infections occurred among 72 (60%) patients (Table 2). The most common infections were pneumonia, bloodstream, surgical site, and urinary. Most infections were caused by bacteria, specifically Enterobacerales and Enterococci. (Table 2) Stool microbial Alpha diversity was lower in patients who developed infection; p=0.0026. (Figure 1) Stool microbiome composition also differed significantly between groups. Patients with postoperative infection experienced more single species expansions, most notably Enterococcus and Enterobacterales, which were common etiologies of infection. (Figure 2) Uninfected patients had more abundant obligate anaerobic taxa including Bacteroidetes, Lachnospiraceae, and Ruminococcaceae.Figure 1Alpha and Beta Diversity of Stool Microbiota: A. Stool microbiome alpha-diversity by inverse Simpson p= 0.0026 Wilcoxon. B. Stool microbiome beta-diversity by PcoA Bray-Curtis Dissimilarity p=0.026 PERMANOVA. Conclusion The stool microbiome of HT patients with postoperative infection is marked by lower alpha diversity and notable compositional differences including Enterococci and Enterobacterales expansion coupled with reduced Bacteroidetes, Lachnospiraceae, and Ruminococcaceae. Further study into the interaction between these organisms and the host are needed to better understand their role in infection. Disclosures All Authors: No reported disclosures

  PublisherDOI

• P-2215. Intestinal microbiome and metabolome fluctuations in patients receiving intensive chemotherapy for AML: Results from a pilot, prospective observational study

  Open Forum Infectious Diseases · 2025-01-29

  articleOpen access

  Abstract Background Loss of a diverse intestinal microbiome, particularly through the depletion of anaerobic bacteria, is associated with poor outcomes in people undergoing treatment for leukemia. We present preliminary results from a pilot, prospective observational study characterizing longitudinal changes in the fecal microbiome and metabolome in patients undergoing intensive chemotherapy for newly diagnosed acute myeloid leukemia (AML). Methods We recruited 10 patients with newly diagnosed AML who were hospitalized for intensive chemotherapy. The subjects underwent daily serum and stool collections during the admission for induction chemotherapy and periodic serum and stool collections during subsequent admissions. Metabolome profiling was conducted by targeted GC- and LC-mass spectrometry of serum and stool specimens, and fecal microbiome composition was determined by Shotgun metagenomic sequencing. Clinical characteristics, including responses to chemotherapy and development of infections, were monitored. Results Metagenomic sequencing demonstrated marked variations in microbiome compositions between patients in our cohort. However, microbiome compositions and diversities remained stable within patients who maintained a higher prevalence of obligate anaerobes belonging to the Lachnospiraceae and Bacteroidaceae families. Moreover, despite stable microbiome compositions, we detected large fluctuations in fecal metabolite concentrations, particularly among secondary bile acids and conjugated and unconjugated bile acids, over the course of induction chemotherapy. Our results suggest that preservation of intestinal anaerobes enhances the stability of the microbiome over time, and the metabolic output of an individual’s microbiome is substantially impacted during cancer treatment. Conclusion Studying dynamics of the intestinal microbiome and metabolome during cancer therapy will help identify signals associated with microbiome diversity or disruption. We also plan to use broad targeted and untargeted platforms to identify metabolites in stool or serum that can be used as biomarkers to correlate with microbiome compositions and to identify patients who are at risk for adverse clinical outcomes associated with disrupted microbiomes. Disclosures All Authors: No reported disclosures

  PublisherDOI

• Fecal metabolite profiling identifies critically ill patients with increased 30-day mortality

  Science Advances · 2025-06-06 · 5 citations

  articleOpen access

  Critically ill patients admitted to the medical intensive care unit (MICU) have reduced intestinal microbiota diversity and altered microbiome-associated metabolite concentrations. Metabolites produced by the gut microbiota have been associated with survival of patients receiving complex medical treatments and thus might represent a treatable trait to improve clinical outcomes. We prospectively collected fecal specimens, defined microbiome compositions by shotgun metagenomic sequencing, and quantified microbiota-derived fecal metabolites by mass spectrometry from 196 critically ill patients admitted to the MICU for non-COVID-19 respiratory failure or shock to correlate microbiota features and metabolites with 30-day mortality. Microbiota compositions of the first fecal sample after MICU admission did not independently associate with 30-day mortality. We developed a metabolic dysbiosis score (MDS) that uses fecal concentrations of 13 microbiota-derived metabolites, which predicted 30-day mortality independent of known confounders. The MDS complements existing tools to identify patients at high risk of mortality by incorporating potentially modifiable, microbiome-related, independent contributors to host resilience.

  PublisherDOI

• Modifications of microbiome-derived cell-free RNA in plasma discriminates colorectal cancer samples

  Nature Biotechnology · 2025-07-08 · 9 citations

  article
  PublisherDOI

• Microbiota profiling to predict clinical events post-heart transplantation 3122

  The Journal of Immunology · 2025-11-01

  articleOpen access

  Abstract Description Human studies have correlated changes in microbiota profiles with clinical outcomes including allograft rejection and postoperative infection, but these data exist mostly outside of heart transplantation (HT). The impact of the microbiota and any identified microbial taxa in these clinical HT outcomes is not clear. We have previously identified distinct microbial composition and reduced immunomodulatory metabolite concentrations in peri-transplant fecal samples from HT recipients compared to healthy donors. Here, we investigated the relationship between peri-transplant fecal microbial composition and postoperative infection risk. Metagenomic sequencing was used to determine peri-transplant fecal microbiota profiles of 121 HT recipients and infections occurring in the first 100 days following transplantation were aggregated. We found a strong correlation between reduced gut microbial diversity and incidence of postoperative infection. Notably, patients who developed infections had an expansion of potentially pathogenic taxa, while uninfected patients had more abundant obligate anaerobic taxa. Preliminary data suggests a potential causal relationship between reduced microbial diversity and increased susceptibility to/severity of systemic infection in mice. Further metabolomic profiling may identify additional causative mechanisms for infection and help develop strategies to preserve or restore the microbiome of HT patients. Funding Sources Supported by NIH/NIAID T32AI007090; NIH/NIAID R01 AI115716; UChicago DFI Multidisciplinary Grant Topic Categories Transplantation Immunology (TRAN)

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Frequent coauthors

• Ameet Daftary

  Indiana University – Purdue University Indianapolis

  12 shared

• Eric G. Pamer

  University of Chicago

  12 shared

• Evans Machogu

  Indiana University School of Medicine

  12 shared

• Matthew A. Odenwald

  University of Chicago

  8 shared

• Emerald Adler

  University of Chicago

  7 shared

• Maryam Khalid

  Minhaj University Lahore

  7 shared

• Jaye Boissiere

  University of Chicago

  6 shared

• M.R. Stutz

  Cook County Health and Hospitals System

  6 shared

Labs

• Christopher LehmannPI

Education

• B.S., Microbiology/Biochemistry

  Colorado State University

  2011

• M.D.

  Indiana University

  2015

• Other, Internal Medicine and Pediatrics

  Indiana University

  2019

• Other, Adult and Pediatric Infectious Disease

  University of Chicago

  2023

Awards & honors

• Fellow American Academy of Pediatrics 2022
• Alpha Omega Alpha 2014