Philip Sherman

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Other Academic Appointments

Professor, Department of Pediatrics, Temerty Faculty of Medicine, University of Toronto

Professor, Institute of Medical Science, Temerty Facuulty of Medicine, University of Toronto

Professor, Department of Laboratory Medicine and Pathobiology, University of Toronto

Professor, Faculty of Dentistry, University of Toronto

Senior Scientist, Cell Biology Program, Research Institute, Hospital for Sick Children

At a Glance

• Dr. Sherman’s research program is focused on examining the effects of probiotics, prebiotics, and human milk oligosaccharides on intestinal epithelia in health and disease.
• Specifically, Dr. Sherman and his team investigate how probiotics, prebiotics and micronutrients influence the onset and progression of inflammatory bowel disease (IBD). With the use of in vitro models of bacterial infection and in vivo animal models of IBD the team is able to study the mechanism by which these factors influence disease outcome.
• Research from Dr. Sherman’s lab extends from basic research to clinical trials in both children and adolescents.

About Dr. Philip Sherman

Dr. Sherman is Professor of Paediatrics, Microbiology (Laboratory Medicine and Pathobiology), Nutritional Sciences, and Dentistry at the Hospital for Sick Children, University of Toronto, where he has been on faculty since 1984. He completed medical school at the University of Calgary and training in pediatrics at the University of California, San Francisco. His training in gastroenterology and research was completed at the Hospital for Sick Children in Toronto, Canada and the Walter Reed Army Institute of Research in Washington, DC.

Dr. Sherman is a Past-President of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition, a Past-President of the Canadian Association of Gastroenterology (CAG), and Past Scientific Director of the Canadian Institutes of Health Research (CIHR) Institute of Nutrition, Metabolism, and Diabetes. Dr. Sherman is the recipient of a Canada Research Chair (tier 1) in Gastrointestinal Disease (2001-2022), and his research program is funded currently by the CIHR.

Research Synopsis

Dr. Sherman’s laboratory strives to better understand host-microbe interactions in the gut. With the use of complimentary in vitro tissue culture systems, ex-vivo and in vivo models of inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) (infectious-, stress-, and chemically-induced), and necrotizing enterocolitis, Dr. Sherman and his team study mechanisms by which pathogens (enterohemorrhagic Escherichia coli and adherent invasive E. coli from patients with Crohn’s disease), and other stressors cause disease and how probiotics, prebiotics, and micronutrients (vitamins, polyunsaturated fatty acids) influence disease outcome.

The large and small intestine play a vital role in digestion and nutrient absorption while the diverse microbiome within the gut contributes to health and well-being by protecting against pathogens, immunomodulation, and nutrient metabolism. Changes in gut physiology and dysbiosis (disruptions in gut microbiome) can cause inflammatory bowel diseases (IBD; Crohn’s disease and ulcerative colitis), irritable bowel syndrome (IBS), and necrotizing enterocolitis (NEC), where symptoms can range from chronic intestinal inflammation, severe abdominal pain, bloody diarrhea, or in the case of NEC, death. These diseases can be triggered by an array of factors including pathogens (enterohemorrhagic Escherichia coli and adherent-invasive E. coli) and stress.

Due to the increasing incidence over the past two decades, especially in children and adolescents, it is important to critically evaluate and understand which environmental factors cause and exacerbate disease and to better delineate ways to prevent and treat symptoms. Dr. Sherman’s laboratory investigates the mechanisms by which non-traditional therapies influence the onset and progression of intestinal injury and mucosal inflammation during disease, such as: probiotics (beneficial bacteria that, when ingested in sufficient amounts, provide health benefits to the host); prebiotics (non-digestible food ingredients that promote the growth of beneficial gut bacteria); and dietary micronutrients (vitamin D, vitamin B12, and fats). More recently, Dr. Sherman’s group has been interested in delineating the effects of human milk oligosaccharides (HMOs) in models of necrotizing enterocolitis. With the use of complementary techniques (in vitro, ex vivo, and in vivo models), they study host responses to various enteric pathogens, changes in the gut microbiome in response to injury, and implement various therapeutic strategies to alter the course of disease.

Dr. Sherman’s group demonstrated that prebiotics have the ability to act indirectly through the modulation of resident gut microflora and directly on host intestinal cells to influence inflammatory responses (Wu et al Microbiome. 2017, Wu et al, Scientific Reports. 2017; Johnson-Henry et al., Journal of Nutrition. 2014). In addition, they have shown that probiotics dampen pro-inflammatory immune responses (Vong et al., Journal of Immunology, 2014) and were the first to find that the timing of probiotic administration is crucial in obtaining beneficial effects against intestinal pathogens (Rodrigues et al., Journal of Infectious Diseases. 2012). Dr. Sherman’s team has also demonstrated that dietary vitamin D deficiency predisposes to more severe gut injury in response to challenge with either adherent-invasive Escherichia coli (a bacterium isolated from the terminal ileum of patients with Crohn’s disease (Assa et al., Inflammatory Bowel Diseases Journal. 2015) or Citrobacter rodentium (a murine-specific enteric bacterial pathogen)-induced colonic inflammation (Assa et al., Journal of Infectious Diseases. 2014).

Research findings from Dr. Sherman’s lab are now being translated into prospective randomized controlled clinical studies conducted in children in Canada and the United States (Freedman et al., Clinical Pediatrics. 2015, Freedman et al., Trials. 2014). Dr. Sherman’s research continues to focus on elucidating how probiotics, prebiotics, and micronutrients affect the onset and progression of IBD. Dr. Sherman’s research is funded by the CIHR, after previously receiving funding from Crohn’s and Colitis Canada. He is currently a co-investigator on a research grant with Dr. Daniel Roth, funded by the Bill and Melinda Gates Foundation.

Recent Awards and Distinctions (Selected)

Fellow, North American Society of Pediatric Gastroenterology, Hepatology & Nutrition (2020)

Distinguished Service Award, Canadian Association of Gastroenterology (2018)

National and International Committee Memberships (Current)

Member, Board of Directors, Obesity Canada

Member, Advisory Board, Nestlé-Gerber

Member, Research Advisory Board, Antibe Therapeutics

Recent Publications

1. Asbury MR, Shama S, Sa JY, Bando N, Butcher J, Comelli EM, Copeland JK, Forte V, Kiss A, Sherman PM, Stintzi A, Taibi A, Tomlinson C, Unger S, Wang PW, O'Connor DL; OptiMoM Feeding Group. Human milk nutrient fortifiers alter the developing gastrointestinal microbiota of very-low-birth-weight infants. Cell Host Microbe. 2022 Aug 12:S1931-3128(22)00357-2. doi: 10.1016/j.chom.2022.07.011. Epub ahead of print. PMID: 35987195.
2. Horne RG, Freedman SB, Johnson-Henry KC, Pang XL, Lee BE, Farion KJ, Gouin S, Schuh S, Poonai N, Hurley KF, Finkelstein Y, Xie J, Williamson-Urquhart S, Chui L, Rossi L, Surette MG, Sherman PM. Intestinal Microbial Composition of Children in a Randomized Controlled Trial of Probiotics to Treat Acute Gastroenteritis. Front Cell Infect Microbiol. 2022 Jun 14;12:883163. doi: 10.3389/fcimb.2022.883163. PMID: 35774405; PMCID: PMC9238408.
3. Wu RY, Botts SR, Johnson-Henry KC, Landberg E, Abrahamsson TR, Sherman PM. Variations in the Composition of Human Milk Oligosaccharides Correlates with Effects on Both the Intestinal Epithelial Barrier and Host Inflammation: A Pilot Study. Nutrients. 2022 Feb 28;14(5):1014. doi: 10.3390/nu14051014. PMID: 35267989; PMCID: PMC8912797.
4. Wu RY, Li B, Horne RG, Ahmed A, Lee D, Robinson SC, Zhu H, Cadete M, Alganabi M, Filler R, Johnson-Henry KC, Delgado-Olguin P, Pierro A, Sherman PM. Structure-Function Relationships of Human Milk Oligosaccharides on the Intestinal Epithelial Transcriptome in Caco-2 Cells and a Murine Model of Necrotizing Enterocolitis. Mol Nutr Food Res. 2021 Dec 18:e2100893. doi: 10.1002/mnfr.202100893. Epub ahead of print. PMID: 34921749.
5. Li B, Lee C, Cadete M, O'Connell JS, Alganabi M, Lee D, Ganji N, Miyake H, Botts SR, Johnson-Henry KC, Maattanen P, Sherman PM, Pierro A. Amniotic fluid stem cell administration can prevent epithelial injury from necrotizing enterocolitis. Pediatr Res. 2021 Sep 24. doi: 10.1038/s41390-021-01657-6. Epub ahead of print. PMID: 34561550.
6. Pell LG, Horne RG, Huntley S, Rahman H, Kar S, Islam MS, Evans KC, Saha SK, Campigotto A, Morris SK, Roth DE, Sherman PM. Antimicrobial susceptibilities and comparative whole genome analysis of two isolates of the probiotic bacterium Lactiplantibacillus plantarum, strain ATCC 202195. Sci Rep. 2021 Aug 5;11(1):15893. doi: 10.1038/s41598-021-94997-6. PMID: 34354117; PMCID: PMC8342526.
7. Freedman SB, Horne R, Johnson-Henry K, Xie J, Williamson-Urquhart S, Chui L, Pang XL, Lee B, Schuh S, Finkelstein Y, Gouin S, Farion KJ, Poonai N, Hurley K, Schnadower D, Sherman PM; Pediatric Emergency Research Canada Probiotic Regimen for Outpatient Gastroenteritis Utility of Treatment (PROGUT) Trial Group. Probiotic stool secretory immunoglobulin A modulation in children with gastroenteritis: a randomized clinical trial. Am J Clin Nutr. 2021 Apr 6;113(4):905-914. doi: 10.1093/ajcn/nqaa369. PMID: 34269370; PMCID: PMC8023833.
8. Horne RG, Yu Y, Zhang R, Abdalqadir N, Rossi L, Surette M, Sherman PM, Adeli K. High Fat-High Fructose Diet-Induced Changes in the Gut Microbiota Associated with Dyslipidemia in Syrian Hamsters. Nutrients. 2020 Nov 20;12(11):3557. doi: 10.3390/nu12113557. PMID: 33233570; PMCID: PMC7699731.
9. Koike Y, Li B, Ganji N, Zhu H, Miyake H, Chen Y, Lee C, Janssen Lok M, Zozaya C, Lau E, Lee D, Chusilp S, Zhang Z, Yamoto M, Wu RY, Inoue M, Uchida K, Kusunoki M, Delgado-Olguin P, Mertens L, Daneman A, Eaton S, Sherman PM, Pierro A. Remote ischemic conditioning counteracts the intestinal damage of necrotizing enterocolitis by improving intestinal microcirculation. Nat Commun. 2020 Oct 2;11(1):4950. doi: 10.1038/s41467-020-18750-9. PMID: 33009377; PMCID: PMC7532542.
10. Li B, Lee C, O'Connell JS, Antounians L, Ganji N, Alganabi M, Cadete M, Nascimben F, Koike Y, Hock A, Botts SR, Wu RY, Miyake H, Minich A, Maalouf MF, Zani-Ruttenstock E, Chen Y, Johnson-Henry KC, De Coppi P, Eaton S, Maattanen P, Delgado Olguin P, Zani A, Sherman PM, Pierro A. Activation of Wnt signaling by amniotic fluid stem cell-derived extracellular vesicles attenuates intestinal injury in experimental necrotizing enterocolitis. Cell Death Dis. 2020 Sep 14;11(9):750. doi: 10.1038/s41419-020-02964-2. PMID: 32929076; PMCID: PMC7490270.