Overview

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.

Publications

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
01/2018

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
10/2017

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
09/2017

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
02/2017

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection.
The New England journal of medicine
DOI: 10.1056/nejmoa1602615
PubMed: 28121498
01/2017

CD4+ T Cells Specific for C. difficile Toxins are a Marker of Patients with Active Relapsing Disease.
Open forum infectious diseases
2017

Fecal microbiota transplantation for the intestinal decolonization of extensively antimicrobial-resistant opportunistic pathogens: a review
Infectious Diseases
Amee R. Manges, Theodore S. Steiner, Alissa J. Wright
DOI: 10.1080/23744235.2016.1177199
05/2016

New Insights Into Shiga ToxigenicEscherichia coliPathogenesis: When Less Is More
Journal of Infectious Diseases
Theodore S. Steiner
DOI: 10.1093/infdis/jiv558
01/2016

Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial.
JAMA
DOI: 10.1001/jama.2015.18098
PubMed: 26757463
01/2016

Antimicrobial Resistance in Enteric Gram-Negative Organisms
Scientific American Medicine
2016

Metagenomic Investigation of Plasma in Individuals with ME/CFS Highlights the Importance of Technical Controls to Elucidate Contamination and Batch Effects.
PLoS ONE
DOI: 10.1371/journal.pone.0165691
PubMed: 27806082
2016

Infections due to Escherichia coli and Other Enteric Gram-Negative Bacilli
Scientific American Medicine
2016

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
12/2015

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
10/2015

CLINICAL PROBLEM-SOLVING. A Surprising Cause of Chronic Cough.
The New England journal of medicine
DOI: 10.1056/nejmcps1303787
PubMed: 26244310
08/2015

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
07/2015

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
05/2015

Diagnosis and Management of Foodborne Infectious Diseases
Food Microbiology
Ted Steiner
DOI: 10.1201/b19874-8
2015

Brain-derived neurotrophic factor concentration may not be depressed in chronic fatigue syndrome
Fatigue: Biomedicine, Health & Behavior
David M. Patrick and Ruth R. Miller and Theodore Steiner and Jennifer L. Gardy and Shoshana M. Parker and Patrick Tang
DOI: 10.1080/21641846.2015.1024004
2015

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
2015

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

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
12/2014

Meta-analysis in microbiology
Indian Journal of Medical Microbiology
H Jarjanazi, TS Steiner, N Pabalan
DOI: 10.4103/0255-0857.136547
2014

Treating Foodborne Illness
Infectious Disease Clinics of North America
Theodore Steiner
DOI: 10.1016/j.idc.2013.05.006
09/2013

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
05/2013

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
03/2013

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
2013

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
2013

ATP conditions intestinal epithelial cells to an inflammatory state that promotes components of DC maturationImmunodulation
European Journal of Immunology
Yu Yao, Megan K. Levings, Theodore S. Steiner
DOI: 10.1002/eji.201142213
10/2012

Regulatory T-cell therapy for inflammatory bowel disease: more questions than answers.
Immunology
DOI: 10.1111/j.1365-2567.2012.03572.x
PubMed: 22348589
06/2012

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
01/2012

Escherichia Coli Enteric Infections
Goldman's Cecil Medicine
Theodore S. Steiner, Richard L. Guerrant
DOI: 10.1016/b978-1-4377-1604-7.00312-2
2012

Environmental influences on T regulatory cells in inflammatory bowel disease
Seminars in Immunology
Gijs Hardenberg, Theodore S. Steiner, Megan K. Levings
DOI: 10.1016/j.smim.2011.01.012
04/2011

Human CD4+ FOXP3+ regulatory T cells produce CXCL8 and recruit neutrophils.
European journal of immunology
DOI: 10.1002/eji.201040459
PubMed: 21268001
02/2011

The stress signal extracellular ATP modulates antiflagellin immune responses in intestinal epithelial cells.
Inflammatory bowel diseases
DOI: 10.1002/ibd.21428
PubMed: 20722064
01/2011

Enteric Escherichia coli Infections
Tropical Infectious Diseases: Principles, Pathogens and Practice
Theodore S. Steiner, Nathan M. Thielman, Richard L. Guerrant
DOI: 10.1016/b978-0-7020-3935-5.00015-x
2011

Endoplasmic reticulum stress modulates TLR responses in intestinal epithelial cellsP-235.
Inflammatory Bowel Diseases
Theodore Steiner, Jiyoung Hwang, David Shin, Yu Yao
DOI: 10.1097/00054725-201112002-00269
2011

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
09/2010

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
03/2010

TLR5 is not required for flagellin-mediated exacerbation of DSS colitis.
Inflammatory bowel diseases
DOI: 10.1002/ibd.21097
PubMed: 19774646
03/2010

Autoactivation of the AggR regulator of enteroaggregativeEscherichia coli in vitroandin vivo
FEMS Immunology & Medical Microbiology
Nicholas Morin, Chelsea Tirling, Sabine M. Ivison, Ajinder Pal Kaur, James P. Nataro, Theodore S. Steiner
DOI: 10.1111/j.1574-695x.2010.00645.x
01/2010

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
2010

Principles and Syndromes of Enteric Infection
Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases
THEODORE S. STEINER and RICHARD L. GUERRANT
DOI: 10.1016/b978-0-443-06839-3.00093-x
2010

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
2010

Dexamethasone in Cryptococcus 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
08/2009

Spread of Cryptococcus gattii into Pacific Northwest region of the United States.
Emerging infectious diseases
DOI: 10.3201/eid1508.081384
PubMed: 19757550
08/2009

S1654 Intrarectal ATP Increases the Severity of DSS Colitis and Augments Anti-Flagellin Antibody Production
Gastroenterology
Sabine M. Ivison, Matthew Mayer, Theodore S. Steiner
DOI: 10.1016/s0016-5085(09)61100-8
05/2009

T1711 ATP Augments Intestinal Epithelial Inflammatory Responses to Flagellin
Gastroenterology
Sabine M. Ivison, Megan HImmel, Jonathan Delano, Nancy Y. Yao, Theodore S. Steiner
DOI: 10.1016/s0016-5085(09)62592-0
05/2009

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
10/2008

The role of T-regulatory cells and Toll-like receptors in the pathogenesis of human inflammatory bowel disease.
Immunology
DOI: 10.1111/j.1365-2567.2008.02939.x
PubMed: 18798918
10/2008

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
04/2008

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
05/2007

Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production.
International immunology
DOI: 10.1093/intimm/dxm014
PubMed: 17329235
04/2007

How flagellin and toll-like receptor 5 contribute to enteric infection.
Infection and immunity
DOI: 10.1128/iai.01506-06
PubMed: 17118981
02/2007

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
01/2007

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
08/2006

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
12/2005

Enteroaggregative Escherichia coli flagellin-induced interleukin-8 secretion requires Toll-like receptor 5-dependent p38 MAP kinase activation.
Immunology
DOI: 10.1111/j.1365-2567.2004.01923.x
PubMed: 15270737
08/2004

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
03/2003

Two Nonadjacent Regions in EnteroaggregativeEscherichia coliFlagellin Are Required for Activation of Toll-like Receptor 5
Journal of Biological Chemistry
Meghan A. Donnelly, Theodore S. Steiner
DOI: 10.1074/jbc.m206851200
08/2002

Mechanisms of emerging diarrheagenic Escherichia coli infection
Current Infectious Disease Reports
Mohammed A. Khan, Ted S. Steiner
DOI: 10.1007/s11908-002-0050-y
03/2002

Enteroaggregative and Diffusely Adherent Escherichia Coli
Escherichia Coli
James P. Nataro, Theodore Steiner
DOI: 10.1016/b978-012220751-8/50007-0
2002

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
09/2001

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
02/2001

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
06/2000

Failure of amphotericin B colloidal dispersion in the treatment of paracoccidioidomycosis.
The American journal of tropical medicine and hygiene
PubMed: 10344661
05/1999

How Intestinal Bacteria Cause Disease
The Journal of Infectious Diseases
Richard L. Guerrant, Ted S. Steiner, Aldo A. M. Lima, David A. Bobak
DOI: 10.1086/513845
03/1999

Intestinal secretory factor released by macrophages stimulated with Clostridium difficile toxin A: role of interleukin 1beta.
Infection and immunity
PubMed: 9746596
10/1998

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
01/1998

Fecal lactoferrin, interleukin-1beta, and interleukin-8 are elevated in patients with severe Clostridium difficile colitis.
Clinical and diagnostic laboratory immunology
PubMed: 9384296
11/1997

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
1997

Diarrhea, demography and cell signaling: lessons from microbial toxins.
Transactions of the American Clinical and Climatological Association
PubMed: 9108674
1997

The pathogenesis of and host response to Cryptosporidium parvum
Current Opinion in Infectious Diseases
Ted S. Steiner, Richard L. Guerrant
DOI: 10.1097/00001432-199606000-00005
06/1996

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
06/1996

Secretin receptors mediating rat forestomach relaxation.
The American journal of physiology
PubMed: 8498512
05/1993

Enteric Escherichia coli Infections
Tropical Infectious Diseases
THEODORE S. STEINER, NATHAN M. THIELMAN, RICHARD L. GUERRANT
DOI: 10.1016/b978-0-443-06668-9.50021-1
1992

Research

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.

Grants

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

May Wong
Jasia Ho
Daniel Lisko
William Rees
Stacy Wang
Dij Mannar, Co-op student