Philip Sherman
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.