The human gut is a very complex system that affects many areas of health. For the gut to work normally, there must be coordination between the immune system, nervous system, and multiple different cell types that line the gut and help it to process and absorb food while fighting infections. The gut also carries a huge number of microbes that play important roles in maintaining its functions. My work focuses on the way that the intestinal immune system functions to fight infections while maintaining normal relationships with the "good" bacteria that normally live in the gut.


Phosphatidylinositol 3-kinase p110d drives intestinal fibrosis in SHIP deficiency.
Mucosal immunology
Lo Y and Sauve JP and Menzies SC and Steiner TS and Sly LM
DOI: 10.1038/s41385-019-0191-z
PubMed: 31358861

Case Report: Ivermectin and Albendazole Plasma Concentrations in a Patient with Disseminated Strongyloidiasis on Extracorporeal Membrane Oxygenation and Continuous Renal Replacement Therapy
The American Journal of Tropical Medicine and Hygiene
Carl Boodman and Michael Libman and Marthe Charles and Yashpal S. Chhonker and Theodore Steiner and Cesilia Nishi and Allison Mah and Daryl J. Murry and Jennifer Grant
DOI: 10.4269/ajtmh.18-0487

Associations of DC-SIGN (CD209) promoter -336G/A polymorphism (rs4804803) with dengue infection: A systematic review and meta-analysis.
Acta tropica
DOI: 10.1016/j.actatropica.2017.10.017
PubMed: 29054571

Adaptive immune response to Clostridium difficile infection: A perspective for prevention and therapy.
European journal of immunology
Rees WD and Steiner TS
DOI: 10.1002/eji.201747295
PubMed: 29272036

2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Shane AL and Mody RK and Crump JA and Tarr PI and Steiner TS and Kotloff K and Langley JM and Wanke C and Warren CA and Cheng AC and Cantey J and Pickering LK
DOI: 10.1093/cid/cix959
PubMed: 29194529

2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
DOI: 10.1093/cid/cix669
PubMed: 29053792

Associations of tumor necrosis factor-a-308 polymorphism with dengue infection: A systematic review and meta-analysis.
Acta tropica
DOI: 10.1016/j.actatropica.2017.05.007
PubMed: 28495402

RNA-Seq Analysis of Gene Expression, Viral Pathogen, and B-Cell/T-Cell Receptor Signatures in Complex Chronic Disease.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
DOI: 10.1093/cid/ciw767
PubMed: 28172519

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection.
The New England journal of medicine
DOI: 10.1056/nejmoa1602615
PubMed: 28121498

CD4+ T Cells Specific for C. difficile Toxins are a Marker of Patients with Active Relapsing Disease.
Open forum infectious diseases

Fecal microbiota transplantation for the intestinal decolonization of extensively antimicrobial-resistant opportunistic pathogens: a review
Infectious Diseases
Amee R. Manges and Theodore S. Steiner and Alissa J. Wright
DOI: 10.1080/23744235.2016.1177199

New Insights Into Shiga ToxigenicEscherichia coliPathogenesis: When Less Is More
Journal of Infectious Diseases
Theodore S. Steiner
DOI: 10.1093/infdis/jiv558

Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial.
DOI: 10.1001/jama.2015.18098
PubMed: 26757463

Metagenomic Investigation of Plasma in Individuals with ME/CFS Highlights the Importance of Technical Controls to Elucidate Contamination and Batch Effects.
DOI: 10.1371/journal.pone.0165691
PubMed: 27806082

Infections due to Escherichia coli and Other Enteric Gram-Negative Bacilli
Scientific American Medicine

Antimicrobial Resistance in Enteric Gram-Negative Organisms
Scientific American Medicine

Evaluation of a Clostridium difficile infection management policy with clinical pharmacy and medical microbiology involvement at a major Canadian teaching hospital.
Journal of clinical pharmacy and therapeutics
DOI: 10.1111/jcpt.12329
PubMed: 26547905

Lyme Disease Diagnosed by Alternative Methods: A Phenotype Similar to That of Chronic Fatigue Syndrome.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
DOI: 10.1093/cid/civ470
PubMed: 26082507

CLINICAL PROBLEM-SOLVING. A Surprising Cause of Chronic Cough.
The New England journal of medicine
DOI: 10.1056/nejmcps1303787
PubMed: 26244310

Tr1 Cells, but Not Foxp3+ Regulatory T Cells, Suppress NLRP3 Inflammasome Activation via an IL-10-Dependent Mechanism.
Journal of immunology (Baltimore, Md. : 1950)
DOI: 10.4049/jimmunol.1403225
PubMed: 26056255

Longitudinal clinical findings and outcome among patients with Cryptococcus gattii infection in British Columbia.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
DOI: 10.1093/cid/civ041
PubMed: 25632012

Diagnosis and Management of Foodborne Infectious Diseases
Food Microbiology
Ted Steiner
DOI: 10.1201/b19874-8

Brain-derived neurotrophic factor concentration may not be depressed in chronic fatigue syndrome
Fatigue: Biomedicine, Health & Behavior
DOI: 10.1080/21641846.2015.1024004

Submaximal exercise testing with near-infrared spectroscopy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients compared to healthy controls: a case-control study.
Journal of translational medicine
DOI: 10.1186/s12967-015-0527-8
PubMed: 25990639

Mediators of Inflammation: Inflammation in Cancer, Chronic Diseases, and Wound Healing
Mediators of Inflammation
Caigan Du and Madhav Bhatia and Sydney C. W. Tang and Mingzhi Zhang and Theodore Steiner
DOI: 10.1155/2015/570653

The worst of both worlds: examining the hypervirulence of the shigatoxigenic/enteroaggregative Escherichia coli O104:H4.
The Journal of infectious diseases
DOI: 10.1093/infdis/jiu400
PubMed: 25038259

Meta-analysis in microbiology
Indian Journal of Medical Microbiology
H Jarjanazi and TS Steiner and N Pabalan
DOI: 10.4103/0255-0857.136547

Treating Foodborne Illness
Infectious Disease Clinics of North America
Theodore Steiner
DOI: 10.1016/j.idc.2013.05.006

Enteroaggregative Escherichia coli and acute diarrhea in children: a meta-analysis of South Asian populations.
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology
DOI: 10.1007/s10096-012-1779-3
PubMed: 23179250

Helios+ and Helios- cells coexist within the natural FOXP3+ T regulatory cell subset in humans.
Journal of immunology (Baltimore, Md. : 1950)
DOI: 10.4049/jimmunol.1201379
PubMed: 23359504

A non-synonymous coding variant (L616F) in the TLR5 gene is potentially associated with Crohn's disease and influences responses to bacterial flagellin.
PloS one
DOI: 10.1371/journal.pone.0061326
PubMed: 23593463

Pulmonary mucormycosis in a patient with Crohn disease on immunosuppressive medications including infliximab.
The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale
DOI: 10.1155/2013/363250
PubMed: 24421803

ATP conditions intestinal epithelial cells to an inflammatory state that promotes components of DC maturation
European Journal of Immunology
Yu Yao and Megan K. Levings and Theodore S. Steiner
DOI: 10.1002/eji.201142213

Regulatory T-cell therapy for inflammatory bowel disease: more questions than answers.
DOI: 10.1111/j.1365-2567.2012.03572.x
PubMed: 22348589

Toll-like receptor 5 deficiency protects from wasting disease in a T cell transfer colitis model in T cell receptor-ß-deficient mice.
Inflammatory bowel diseases
DOI: 10.1002/ibd.21738
PubMed: 22038840

Escherichia Coli Enteric Infections
Goldman's Cecil Medicine
Theodore S. Steiner and Richard L. Guerrant
DOI: 10.1016/b978-1-4377-1604-7.00312-2

Environmental influences on T regulatory cells in inflammatory bowel disease
Seminars in Immunology
Gijs Hardenberg and Theodore S. Steiner and Megan K. Levings
DOI: 10.1016/j.smim.2011.01.012

Human CD4+ FOXP3+ regulatory T cells produce CXCL8 and recruit neutrophils.
European journal of immunology
DOI: 10.1002/eji.201040459
PubMed: 21268001

The stress signal extracellular ATP modulates antiflagellin immune responses in intestinal epithelial cells.
Inflammatory bowel diseases
DOI: 10.1002/ibd.21428
PubMed: 20722064

Enteric Escherichia coli Infections
Tropical Infectious Diseases: Principles, Pathogens and Practice
Theodore S. Steiner and Nathan M. Thielman and Richard L. Guerrant
DOI: 10.1016/b978-0-7020-3935-5.00015-x

Endoplasmic reticulum stress modulates TLR responses in intestinal epithelial cells
Inflammatory Bowel Diseases
Theodore Steiner and Jiyoung Hwang and David Shin and Yu Yao
DOI: 10.1097/00054725-201112002-00269

Oxidative stress enhances IL-8 and inhibits CCL20 production from intestinal epithelial cells in response to bacterial flagellin.
American journal of physiology. Gastrointestinal and liver physiology
DOI: 10.1152/ajpgi.00089.2010
PubMed: 20595617

TLR5 is not required for flagellin-mediated exacerbation of DSS colitis.
Inflammatory bowel diseases
DOI: 10.1002/ibd.21097
PubMed: 19774646

The single IgG IL-1-related receptor controls TLR responses in differentiated human intestinal epithelial cells.
Journal of immunology (Baltimore, Md. : 1950)
DOI: 10.4049/jimmunol.0900021
PubMed: 20130217

Autoactivation of the AggR regulator of enteroaggregativeEscherichia coli in vitroandin vivo
FEMS Immunology & Medical Microbiology
Nicholas Morin and Chelsea Tirling and Sabine M. Ivison and Ajinder Pal Kaur and James P. Nataro and Theodore S. Steiner
DOI: 10.1111/j.1574-695x.2010.00645.x

Principles and Syndromes of Enteric Infection
Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases
DOI: 10.1016/b978-0-443-06839-3.00093-x

Protein kinase D1 and D2 are involved in chemokine release induced by toll-like receptors 2, 4, and 5.
Cellular immunology
DOI: 10.1016/j.cellimm.2010.05.012
PubMed: 20557879

The p110a and p110ß isoforms of class I phosphatidylinositol 3-kinase are involved in toll-like receptor 5 signaling in epithelial cells.
Mediators of Inflammation
DOI: 10.1155/2010/652098
PubMed: 20953381

Dexamethasone inCryptococcus gattiiCentral Nervous System Infection
Clinical Infectious Diseases
Peter Phillips and Kristine Chapman and Madeleine Sharp and Phil Harrison and Jerry Vortel and Theodore Steiner and William Bowie
DOI: 10.1086/603554

Spread of Cryptococcus gattii into Pacific Northwest region of the United States.
Emerging infectious diseases
DOI: 10.3201/eid1508.081384
PubMed: 19757550

T1711 ATP Augments Intestinal Epithelial Inflammatory Responses to Flagellin
Sabine M. Ivison and Megan HImmel and Jonathan Delano and Nancy Y. Yao and Theodore S. Steiner
DOI: 10.1016/s0016-5085(09)62592-0

S1654 Intrarectal ATP Increases the Severity of DSS Colitis and Augments Anti-Flagellin Antibody Production
Sabine M. Ivison and Matthew Mayer and Theodore S. Steiner
DOI: 10.1016/s0016-5085(09)61100-8

Anti-flagellin antibodies in irritable bowel syndrome: another attack on our commensals?
Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
DOI: 10.1111/j.1365-2982.2008.01199.x
PubMed: 18826558

The role of T-regulatory cells and Toll-like receptors in the pathogenesis of human inflammatory bowel disease.
DOI: 10.1111/j.1365-2567.2008.02939.x
PubMed: 18798918

Flagellin-dependent and -independent inflammatory responses following infection by enteropathogenic Escherichia coli and Citrobacter rodentium.
Infection and immunity
DOI: 10.1128/iai.01141-07
PubMed: 18227166

Protein kinase D interaction with TLR5 is required for inflammatory signaling in response to bacterial flagellin.
Journal of immunology (Baltimore, Md. : 1950)
DOI: 10.4049/jimmunol.178.9.5735
PubMed: 17442957

Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production.
International immunology
DOI: 10.1093/intimm/dxm014
PubMed: 17329235

How flagellin and toll-like receptor 5 contribute to enteric infection.
Infection and immunity
DOI: 10.1128/iai.01506-06
PubMed: 17118981

A phosphorylation site in the Toll-like receptor 5 TIR domain is required for inflammatory signalling in response to flagellin.
Biochemical and biophysical research communications
DOI: 10.1016/j.bbrc.2006.11.132
PubMed: 17157808

Infectious diarrhea: new pathogens and new challenges in developed and developing areas.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
DOI: 10.1086/505874
PubMed: 16838227

Human CD4+ T cells express TLR5 and its ligand flagellin enhances the suppressive capacity and expression of FOXP3 in CD4+CD25+ T regulatory cells.
Journal of immunology (Baltimore, Md. : 1950)
DOI: 10.4049/jimmunol.175.12.8051
PubMed: 16339542

Enteroaggregative Escherichia coli flagellin-induced interleukin-8 secretion requires Toll-like receptor 5-dependent p38 MAP kinase activation.
DOI: 10.1111/j.1365-2567.2004.01923.x
PubMed: 15270737

Interleukin-8, tumor necrosis factor-alpha, and lactoferrin in immunocompetent hosts with experimental and Brazilian children with acquired cryptosporidiosis.
The American journal of tropical medicine and hygiene
PubMed: 12685639

Two Nonadjacent Regions in EnteroaggregativeEscherichia coliFlagellin Are Required for Activation of Toll-like Receptor 5
Journal of Biological Chemistry
Meghan A. Donnelly and Theodore S. Steiner
DOI: 10.1074/jbc.m206851200

Mechanisms of emerging diarrheagenic Escherichia coli infection
Current Infectious Disease Reports
Mohammed A. Khan and Ted S. Steiner
DOI: 10.1007/s11908-002-0050-y

Enteroaggregative and Diffusely Adherent Escherichia Coli
Escherichia Coli
James P. Nataro and Theodore Steiner
DOI: 10.1016/b978-012220751-8/50007-0

Role of inducible cyclooxygenase and prostaglandins in Clostridium difficile toxin A-induced secretion and inflammation in an animal model.
The Journal of infectious diseases
DOI: 10.1086/322799
PubMed: 11474431

Practice guidelines for the management of infectious diarrhea.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
DOI: 10.1086/318514
PubMed: 11170940

Enteroaggregative Escherichia coli expresses a novel flagellin that causes IL-8 release from intestinal epithelial cells.
The Journal of clinical investigation
DOI: 10.1172/jci8892
PubMed: 10862792

Failure of amphotericin B colloidal dispersion in the treatment of paracoccidioidomycosis.
The American journal of tropical medicine and hygiene
PubMed: 10344661

How Intestinal Bacteria Cause Disease
The Journal of Infectious Diseases
Richard L. Guerrant and Ted S. Steiner and Aldo A. M. Lima and David A. Bobak
DOI: 10.1086/513845

Intestinal secretory factor released by macrophages stimulated with Clostridium difficile toxin A: role of interleukin 1beta.
Infection and immunity
PubMed: 9746596

Enteroaggregative Escherichia coli produce intestinal inflammation and growth impairment and cause interleukin-8 release from intestinal epithelial cells.
The Journal of infectious diseases
DOI: 10.1086/513809
PubMed: 9419174

Fecal lactoferrin, interleukin-1beta, and interleukin-8 are elevated in patients with severe Clostridium difficile colitis.
Clinical and diagnostic laboratory immunology
PubMed: 9384296

Protozoal agents: what are the dangers for the public water supply?
Annual review of medicine
DOI: 10.1146/annurev.med.48.1.329
PubMed: 9046966

Diarrhea, demography and cell signaling: lessons from microbial toxins.
Transactions of the American Clinical and Climatological Association
PubMed: 9108674

The pathogenesis of and host response to Cryptosporidium parvum
Current Opinion in Infectious Diseases
Ted S. Steiner and Richard L. Guerrant
DOI: 10.1097/00001432-199606000-00005

New evidence for an inflammatory component in diarrhea caused by selected new, live attenuated cholera vaccines and by El Tor and Q139 Vibrio cholerae.
Infection and immunity
PubMed: 8675353

Secretin receptors mediating rat forestomach relaxation.
The American journal of physiology
PubMed: 8498512

Enteric Escherichia coli Infections
Tropical Infectious Diseases
DOI: 10.1016/b978-0-443-06668-9.50021-1


Current Projects
My current research program targets two very important intestinal diseases: C. difficile infection and inflammatory bowel disease. C. difficile is the leading cause of hospital-acquired infections in Canada, and can lead to debilitating or even fatal diarrhea. I am exploring the role of the immune system in protecting against C. difficile by studying specific types of immune responses in people with their first episode of infection and comparing them to people with recurrent infections. I also have several clinical projects examining the benefit of fecal microbial transplantation (FMT), also known as "stool transplant", to control these recurrent infections.

My second main project is to develop a new treatment for inflammatory bowel disease (IBD; ulcerative colitis and Crohn's disease) based on the realization that people with these diseases develop abnormal immune responses to normal gut bacteria. It is believed that these responses "trick" the gut into thinking there is a bad infection, so it mobilizes its "army" of white blood cells into the gut, leading to unwanted inflammation that damages the gut. We are working to take advantage of these abnormal responses by making "super-suppressor" cells that reduce inflammation when they sense a major bacterial protein, flagellin, which is present in large amounts in the gut. We are also examining the types of immune responses that people with IBD make against flagellin to better understand how they cause damage.


Canadian Institutes of Health Research (CIHR) Project Grant 2017-2021

Canadian Institutes of Health Research (CIHR) Operating Grant 2017-2019

Crohn's & Colitis Foundation of Canada (CCFC) Grants in Aid of Research 2016-2019

Research Group Members

Daniel Lisko
Laura Oliveira, Clinical Research Coordinator
William Rees
Rene Tandun, Student
Stacy Wang
May Wong, Research Technician
Enoch Yau, Co-op Student