About

Eugene B. Chang is the Martin Boyer Professor of Medicine at the University of Chicago, affiliated with the Department of Medicine. His research group focuses on studying intestinal microbes and their interactions with the host, emphasizing the importance of the microbiome in human health. Dr. Chang's work explores how environmental and lifestyle changes over the past century may have altered the human microbiome, contributing to the rise of disorders such as diabetes, obesity, metabolic syndrome, cancer, and autoimmune diseases. His research aims to understand the factors influencing the assembly of intestinal microbial communities and to harness this knowledge for disease prevention and treatment. Employing advanced microbial analysis, genetically modified and gnotobiotic mouse models, metabolic profiling, and bioinformatics, Dr. Chang's lab investigates both host and microbiome dynamics. He is actively involved in multiple academic committees, including Cancer Biology, Immunology, Microbiology, and Molecular Metabolism and Nutrition, and has received several awards for his contributions to the field.

Research topics

• Biology
• Immunology
• Medicine
• Bioinformatics
• Internal medicine
• Pathology
• Sociology
• Microbiology
• Biochemistry
• Virology
• Evolutionary biology
• Cancer research
• Computational biology
• Endocrinology
• Cell biology
• Surgery
• Neuroscience
• Gastroenterology
• Chemistry
• Ecology
• Genetics

Selected publications

• 485 MATERNAL FOOD ADDITIVE INTAKE REPROGRAM OFFSPRING IMMUNITY VIA GUT MICROBIOTA-INDUCED IMPAIRMENT OF HISTIDINE METABOLISM (MOMMY-IBD STUDY)

  Gastrointestinal Endoscopy · 2026-05-01

  article
  PublisherDOI

• Short-term sleep restriction in humans alters diurnal circulating metabolite profiles, including those of microbial origin

  Journal of Clinical Investigation · 2026-03-15

  articleOpen access

  BACKGROUNDGut microbes and their metabolites contribute to the host circulating metabolome and exhibit diurnal variation influenced by sleep-wake cycles and meal timing. Sleep deprivation alters the rhythmic circulating metabolome, but its impact on microbial metabolites remains unclear. We tested whether 24-hour circulating metabolite profiles, including those of microbial origin, differ under normal (habitual) versus short-term restricted sleep.METHODSIn a randomized crossover design, 9 healthy adults completed 2 in-lab 24-hour blood sampling sessions (q120): one following 3 nights of normal sleep (8.5 hours/night), the other following 3 nights of sleep restriction (4.5 hours/night). Meal timing and caloric intake were held constant. Serum metabolites were characterized using untargeted reverse-phase liquid chromatography-mass spectrometry and rhythmicity was assessed using empirical JTK_CYCLE analysis.RESULTSWe identified 90 metabolites, including 14 of microbial origin or derived from host metabolism of microbial products, e.g., butyrate and tryptophan derivatives. Sleep restriction significantly altered serum metabolite composition compared with normal sleep. While many compounds maintained rhythmicity across conditions, sleep restriction disrupted rhythms of several key compounds, including microbe-derived metabolites. Notably, butyrate and indole-3-propionic acid lost rhythmicity, whereas new rhythms emerged in the tryptophan catabolite, kynurenine, and lipid metabolism intermediates.CONCLUSIONWe provide evidence that microbial metabolites are detectable in human blood and exhibit sleep-dependent rhythmicity. Sleep restriction alters diurnal circulating microbial and host-derived metabolite rhythms even under constant meal timing, composition, and calories. These findings support links between host sleep patterns and gut microbial metabolism and suggest microbial metabolites as potential biomarkers or mediators of sleep loss-associated health risks.TRIAL REGISTRATIONNCT00989976.FUNDINGNIH/NCRR KL2RR025000; R56DK102872-01A1, P30DK020595; P30DK042086; K01DK111785; F31DK122714; DOD W81XWH-07-2-0071.

  PublisherDOI

• 485 MATERNAL FOOD ADDITIVE INTAKE REPROGRAM OFFSPRING IMMUNITY VIA GUT MICROBIOTA-INDUCED IMPAIRMENT OF HISTIDINE METABOLISM (MOMMY-IBD STUDY)

  Gastroenterology · 2026-05-01

  article
  PublisherDOI

• 1004: MATERNAL FOOD ADDITIVE ALTERS OFFSPRING’S EARLY LIFE MICROBIOME AND DRIVES TRANSGENERATIONAL SUSCEPTIBILITY TO COLITIS AND IMMUNE DYSREGULATION (MOMMY-IBD STUDY)

  Gastroenterology · 2025-05-01

  articleOpen access
  PublisherDOI

• Microbiome mismatches from microbiota transplants lead to persistent off-target metabolic and immunomodulatory effects

  Cell · 2025-06-06 · 36 citations

  articleSenior author
  PublisherDOI

• Histopathologic Evaluation and Single-cell Spatial Transcriptomics of the Colon Reveal Cellular and Molecular Abnormalities Linked to J-Pouch Failure in Patients With Inflammatory Bowel Disease

  Cellular and Molecular Gastroenterology and Hepatology · 2025-01-01

  articleOpen access

  BACKGROUND & AIMS: Total abdominal colectomy (TAC) with a staged ileal pouch-anal anastomosis (IPAA) is a common surgical treatment for ulcerative colitis (UC). However, a significant percentage of patients experience pouch failure, leading to morbidity. This retrospective case-control study identified histopathologic features of the TAC specimen associated with pouch failure and investigated the molecular mechanisms of this susceptibility using single-cell spatial transcriptomics. METHODS: We analyzed a cohort of 417 patients who underwent IPAA between 2000 and 2010 at the University of Chicago Medical Center for up to 18 years. Histologic examination of TAC specimens focused on disease activity, depth of inflammation, and specific features, including granulomas and deep ulcers. A subset of patients was profiled using single-cell spatial transcriptomics to map gene expression and immune cell interactions in relation to the risk of pouch failure. RESULTS: macrophage infiltration is associated with increased risk of future pouch failure. CONCLUSION: Histologic features including CD68 immunohistochemisty and spatial molecular profiling are predictive of IPAA failure. These findings support the use of histologic evaluation and targeted molecular analysis of the TAC specimen to identify high-risk patients and improve IPAA outcomes.

  PublisherDOI

• A prometabolite strategy inhibits cardiometabolic disease in an ApoE–/– murine model of atherosclerosis

  JCI Insight · 2025-08-08 · 2 citations

  articleOpen access

  Butyrate, a microbiome-derived short-chain fatty acid with pleiotropic effects on inflammation and metabolism, has been shown to significantly reduce atherosclerotic lesions, rectify routine metabolic parameters such as low-density lipoprotein cholesterol (LDL-C), and reduce systemic inflammation in murine models of atherosclerosis. However, its foul odor, rapid metabolism in the gut and thus low systemic bioavailability limit its therapeutic effectiveness. Our laboratory has engineered an ester-linked L-serine conjugate to butyrate (SerBut) to mask its taste and odor and to coopt amino acid transporters in the gut to increase its systemic bioavailability, as determined by tissue measurements of free butyrate, produced by hydrolysis of SerBut. In an apolipoprotein E-knockout (ApoE)-/- mouse model of atherosclerosis, SerBut reduced systemic LDL-C, proinflammatory cytokines, and circulating neutrophils. SerBut enhanced inhibition of plaque progression and reduced monocyte accumulation in the aorta compared with sodium butyrate. SerBut suppressed liver injury biomarkers alanine transaminase and aspartate aminotransferase and suppressed steatosis in the liver. SerBut overcomes several barriers to the translation of butyrate and shows superior promise in slowing atherosclerosis and liver injury compared with equidosed sodium butyrate.

  PublisherOA PDFDOI

• Assessing the health of the gut microbial organ: why and how?

  Journal of Clinical Investigation · 2025-06-01 · 1 citations

  articleOpen accessSenior author
  PublisherDOI

• Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients

  Nature Communications · 2025-01-21 · 8 citations

  articleOpen access

  Total proctocolectomy with ileal pouch anal anastomosis is the standard of care for patients with severe ulcerative colitis. We generated a cell-type-resolved transcriptional and epigenetic atlas of ileal pouches using scRNA-seq and scATAC-seq data from paired biopsy samples of the ileal pouch and the ileal segment above the pouch (pre-pouch) from patients (male=4, female=2), and paired biopsies of the terminal ileum and ascending colon from healthy individuals (male=3, female=3) serving as reference. Our study finds an additional population of absorptive and secretory epithelial cells within the pouch but not the pre-pouch. These pouch-specific enterocytes express a subset of colon-specific genes, including CEACAM5 and CD24. However, compared to normal colonocytes, expression of these genes is lower, and these enterocytes also express inflammatory and secretory genes while maintaining expression of some ileal-specific genes. This cell-type-resolved transcriptomic and epigenetic atlas of the ileal pouch establishes a reference for investigating pouch physiology and pathology. Patients with refractory ulcerative colitis often undergo ileal pouch anal anastomosis forming an ileal pouch. Here the authors use a single-cell genomics approach to show that ileal pouches from ulcerative colitis patients feature a unique type of enterocytes which express colonocyte-specific and inflammatory genes while also retaining expression of ileal marker genes.

  PublisherOA PDFDOI

• Histopathologic Evaluation and Single-Cell Spatial Transcriptomics of the Colon Reveal Cellular and Molecular Abnormalities Linked to J-Pouch Failure in Patients with Inflammatory Bowel Disease

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-28

  preprintOpen access

  Background and Aims: Total abdominal colectomy (TAC) with a staged ileal pouch-anal anastomosis (IPAA) is a common surgical treatment for ulcerative colitis (UC). However, a significant percentage of patients experience pouch failure, leading to morbidity. This retrospective case-control study identified histopathological features of the TAC specimen associated with pouch failure and investigated the molecular mechanisms of this susceptibility using single-cell spatial transcriptomics. Methods: We analyzed a cohort of 417 patients who underwent IPAA between 2000-2010 at the University of Chicago Medical Center for up to 18 years. Histological examination of TAC specimens focused on disease activity, depth of inflammation, and specific features, including granulomas and deep ulcers. A subset of patients was profiled using single-cell spatial transcriptomics to map gene expression and immune cell interactions in relation to the risk of pouch failure. Results: The 18-year pouch failure risk was 23%, with post-procedure diagnosis of CD as a major risk factor (HR = 4.3, 95% CI: 2.3-8.1) as well as high-risk histologic features, including deep chronic inflammation (HR = 21, 95% CI: 11-41) and severe disease activity (HR = 14, 95% CI: 5.7-32) in TAC specimens. Spatial transcriptomics showed immune infiltration of T and myeloid cells, reduced myocyte-glial interactions, and cytokine signaling pathways such as IL-10, IL-1β, and type I/II interferons, associated with an increased risk of pouch failure. Conclusion: Histological features and spatial molecular profiling are predictive of IPAA failure. These findings support the use of histologic evaluation and targeted molecular analysis of the TAC specimen to identify high-risk patients and improve IPAA outcomes.

  PublisherDOI

Recent grants

• NIH Grant R01DK047722

  NIH · $5.6M · 2022

• NIH Grant R21HG004858

  NIH · $414k · 2010

• NIH Grant R01DK040922

  NIH · $532k · 1992

• NIH Grant R23AM035096

  NIH · $81k · 1985

• Conceptual and mechanistic insights into the development of diet-induced obesity through disruption of hepatic circadian rhythms by the gut microbiome

  NIH · $2.4M · 2019–2022

Frequent coauthors

• Mark W. Musch

  University of Chicago

  183 shared

• Yunwei Wang

  Liuzhou General Hospital

  89 shared

• Jack A. Gilbert

  University of California, San Diego

  88 shared

• Vanessa Leone

  University of Wisconsin–Madison

  75 shared

• Mrinalini C. Rao

  University of Illinois Chicago

  58 shared

• Casey T. Weaver

  University of Alabama at Birmingham

  49 shared

• Kristen L. Dennis

  49 shared

• Shuya Wang

  Central South University

  49 shared

Labs

• Eugene B. Chang LabPI

Awards & honors

• Takeda Distinguished Scientist Award Takeda, Inc. (2014)
• National Diabetes and Digestive and Kidney Disease Advisory…
• AGA Outstanding Mentorship award American Gastroenterologica…
• NIH Merit Award National Institutes of Health (2008 - 2018)