Dr Christopher Stewart
- Email: firstname.lastname@example.org
- Telephone: 01912825335
- Address: Institute of Cellular Medicine
M3.061, William Leech Building,
Newcastle upon Tyne,
The number of babies surviving preterm birth is increasing, resulting in increasing numbers of neonates susceptible to preterm disease. The most common diseases affecting preterm infants are necrotising enterocolitis (NEC; leaky gut) and late onset sepsis (LOS; bacteria in blood). The main risk factors for these diseases are immaturity of the neonate and abnormal bacterial colonization. However, despite several decades of study, the mechanisms of these diseases remain poorly understood, with no single or combination of bacteria reproducibly shown to cause disease.
‘The Great North Neonatal Biobank’ (http://www.ncl.ac.uk/biobanks/collections/neonatal/) has a large collection of samples from preterm or newborn babies with complex health needs. Using this resource, we identified a unique bacterial community that only occurred in the gut of control infants. This community had a high overall diversity and was rich in bifidobacteria, which is considered a ‘healthy bacteria’.
While immensely informative for hypothesis generation, clinical samples are not well suited to determine mechanisms involved in disease pathobiology. Furthermore, animal models of prematurity prevent clear translatability into human populations. Advancing existing high-throughput discovery work, my research seeks to interrogate microbial-host cross-talk using a novel and powerful co-culture model that accurately mimics the conditions of the gastrointestinal tract. The model utilises patient tissue that would otherwise be discarded to derive intestinal ‘enteroids’. Human intestinal enteroids grow into ‘mini guts’ and the co-culture model permits the addition of anaerobic bacteria to the patient derived enteroids. This allows us to determine how bacteria (the microbiome) influence health and disease.
This ex vivo modeling promises to lead to major advances in our understanding of how microbes promote health, or cause disease, in the gut of preterm infants. The developed methodologies can also be applied to study microbial-host cross-talk in a wide range of gastrointestinal disease beyond preterm infants, including diseases affecting pediatric and adult populations.
Such knowledge from the basic science has great potential for the development of new treatments and clinical management of patients.
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My research interests are focused on the ecology of microbial communities and host responses in human health and disease. My research typically focuses on early life (neonatal through to childhood) and is split into two major areas:
1) Multi-omic investigation of clinical samples: Applying high-throughput next generation sequencing and mass spectrometry based approaches to generate large datasets from clinical samples, including stool, nasopharyngeal aspirate, saliva, oral swabs, tissue resections, and blood. Such datasets typically include information relating to the presence of microbes and their genetic capacity, as well as microbial and host protein and metabolite levels. Bioinformatics and statistical analysis can then be applied to determine differences between diseased and control groups, plus what specific microbes/genes/proteins/metabolites are associated with each group. Although disease mechanism requires further work, this area of discovery research typically yields several testable hypotheses.
2) Novel models to elucidate microbial-host crosstalk and interrogate the mechanisms of gastrointestinal disease: The potential to interrogate microbial-host cross-talk promises to lead to major advances in our understanding of how microbes promote health or cause disease. Due to recent scientific advances we now have the ability to take patient tissue that would otherwise be discarded and derive intestinal ‘enteroids’ from the tissue. These human intestinal enteroids are able to grow into ‘mini guts’ in the laboratory and can differentiate into all the major cell types of the intestine. They also secrete mucin and respond to viral or bacterial infection. Because the tissue is derived from patients with disease, and retains the genetic, epigenetic, and exposure history, human intestinal enteroids have several major advances over animal models. With collaborators at Baylor College of Medicine (Houston, USA), we have pioneered a powerful co-culture system that mimics the conditions of the gastrointestinal tract and simultaneously allows bacteria and patient derived enteroids to interact directly. We can then test how the addition of specific bacteria influences the health or disease status of the cells, such as by measuring epithelial integrity, bacterial translocation, and markers of disease (e.g., inflammatory cytokines). This work allows microbial-host cross-talk to be investigated and can lead to mechanistic understanding of disease processes, which can be directly translated into clinical care of patients.
- Houghton D, Stewart CJ, Stamp C, Nelson A, Ajami NJ, Petrosino JF, Wipat A, Trenell MI, Turnbull DM, Greaves LC. Age-related mitochondrial dysfunction influences the mouse intestinal microbiome composition. The Journals of Gerontology: Series A, Biological Sciences & Medical Sciences 2018, 73(5), 571-578.
- Hasegawa K, Stewart CJ, Celedón JC, Mansbach JM, Tierney C, Camargo CA. Circulating 25-hydroxyvitamin D, nasopharyngeal airway metabolome, and bronchiolitis severity. Allergy 2018, epub ahead of print.
- Stewart CJ, Auchtung TA, Ajami NJ, Velasquez K, Smith DP, DeLaGarzaII R, Salas R, Petrosino JF. Effects of tobacco smoke and electronic cigarette vapor exposure on the oral and gut microbiota in humans: a pilot study. PeerJ 2018, 6, e4693.
- Auchtung T, Fofanova T, Stewart CJ, Nash A, Wong M, Gesell J, Auchtung A, Ajami N, Petrosino J. Investigating Colonization of the Healthy Adult Gastrointestinal Tract by Fungi. mSphere 2018, 3(2), e00092-18.
- Valentine G, Chu DM, Stewart CJ, Aagaard KM. Relationships between Perinatal Interventions, Maternal-Infant Microbiomes, and Neonatal Outcomes. Clinics in Perinatology 2018, Epub ahead of print.
- Stewart CJ, Hasegawa K, Wong MC, Ajami NJ, Petrosino JF, Piedra PA, Espinola JA, Tierney CN, Camargo CA, Mansbach JM. Respiratory syncytial virus and rhinovirus bronchiolitis are associated with distinct metabolic pathways. Journal of Infectious Diseases 2018, Accepted manuscript.
- Hasegawa K, Stewart CJ, Celedón JC, Mansbach JM, Tierney C, Camargo CA. Serum 25-hydroxyvitamin D, metabolome, and bronchiolitis severity among infants - A multicenter cohort study. Pediatric Allergy and Immunology 2018, e-pub ahead of print.
- Houghton D, Hardy T, Stewart C, Errington L, Day CP, Trenell MI, Avery L. Systematic review assessing the effectiveness of dietary intervention on gut microbiota in adults with type 2 diabetes. Diabetologia 2018, Epub ahead of print.
- Stewart CJ, Mansbach JM, Wong MC, Ajami NJ, Petrosino JF, Camargo CA, Hasegawa K. Associations of nasopharyngeal metabolome and microbiome with severity among infants with bronchiolitis: A multiomic analysis. American Journal of Respiratory and Critical Care Medicine 2017, 196(7), 882-891.
- Zalewski S, Stewart CJ, Embleton ND, Berrington JE. Brief guide to the analysis, interpretation, and presentation of microbiota data. Archives of Disease in Childhood: Education and Practice Edition 2017, Epub ahead of print.
- Stewart CJ, Embleton ND, Clements E, Luna PN, Smith DP, Fofanova TY, Nelson A, Taylor G, Orr CH, Petrosino JF, Berrington JE, Cummings SP. Cesarean or vaginal birth does not impact the longitudinal development of the gut microbiome in a cohort of exclusively preterm infants. Frontiers in Microbiology 2017, 8, 1008.
- O'Neil DS, Stewart CJ, Chu DM, Goodspeed DM, Gonzalez-Rodriguez PJ, Shope CD, Aagaard KM. Conditional postnatal deletion of the neonatal murine hepatic circadian gene, Npas2, alters the gut microbiome following restricted feeding. American Journal of Obstetrics and Gynecology 2017, 217(2), 218.e1-218.e15.
- Stewart CJ, Cummings SP. Early Life Gut Microbiome. In: Crystal D Karakochuk, Kyly C. Whitfield, Tim J Green, Klaus Kraemer, ed. The Biology Behind the First 1,000 Days of Life. USA: CRC Press/Taylor & Francis Group, 2017.
- Brabin L, Roberts S, Gies S, Nelson A, Diallo S, Stewart CJ, Kazienga A, Birtles J, Ouedraogo S, Claeys Y, Tinto H, d'Alessandro H, Faragher B, Brabin B. Effects of long-term weekly iron and folic acid supplementation on lower genital tract infection - a double blind, randomised controlled trial in Burkina Faso. BMC Medicine 2017, 15(1), 206.
- Stewart CJ, Nelson A, Campbell MD, Walker M, Stevenson EJ, Shaw JA, Cummings SP, West DJ. Gut microbiota of Type 1 diabetes patients with good glycaemic control and high physical fitness is similar to people without diabetes: an observational study. Diabetic Medicine 2017, 34(1), 127-134.
- Houghton D, Stewart CJ, Stamp C, Nelson A, Ajami NJ, Petrosino JF, Wipat A, Trenell MI, Turnbull DM, Greaves LC. Impact of Age-Related Mitochondrial Dysfunction and Exercise on Intestinal Microbiota Composition. The Journals of Gerontology: Series A 2017, glx197.
- Stewart CJ, Embleton ND, Marrs ECL, Smith DP, Fofanova T, Nelson A, Skeath T, Perry JD, Petrosino JF, Berrington JE, Cummings SP. Longitudinal development of the gut microbiome and metabolome in preterm neonates with late onset sepsis and healthy controls. Microbiome 2017, 5(1), 75.
- Embleton ND, Berrington JE, Dorling J, Ewer AK, Juszczak E, Kirby JA, Lamb CA, Lanyon CV, McGuire W, Probert CS, Rushton SP, Shirley MD, Stewart CJ, Cummings SP. Mechanisms Affecting the Gut of Preterm Infants in Enteral Feeding Trials. Frontiers in Microbiology 2017, 4, 14.
- Hasegawa K, Stewart CJ, Mansbach JM, Linnemann RW, Ajami NJ, Petrosino JF, Camargo CA. Sphingolipid metabolism potential in fecal microbiome and bronchiolitis in infants: A case-control study. BMC Research Notes 2017, 10(1), 325.
- Nash AK, Auchtung TA, Wong MC, Smith DP, Gesell JR, Ross MC, Stewart CJ, Metcalf GA, Muzny DM, Gibbs RA, Ajami NJ, Petrosino JF. The gut mycobiome of the Human Microbiome Project healthy cohort. Microbiome 2017, 5(1), 153.
- Skeath T, Stewart CJ, Waugh S, Embleton ND, Cummings SP, Berrington JE. Cytomegalovirus and other common enteric viruses are not commonly associated with Necrotizing Enterocolitis. Acta Paediatrica 2016, 105(1), 50-52.
- Lane JP, Stewart CJ, Cummings SP, Gennery AR. Functional changes in gut microbiota during hematopoietic stem cell transplantation for severe combined immunodeficiency. Journal of Allergy and Clinical Immunology 2016, 138(2), 622-625.
- Houghton D, Stewart C, Day C, Trenell M. Gut microbiota and lifestyle interventions in NAFLD. International Journal of Molecular Sciences 2016, 17(4), 447.
- Stewart CJ, Nelson A, Treumann A, Skeath T, Cummings SP, Embleton ND, Berrington JE. Metabolomic and proteomic analysis of serum from preterm infants with necrotising entercolitis and late-onset sepsis. Pediatric Research 2016, 79(3), 425-431.
- Al-Momani H, Perry A, Stewart CJ, Jones R, Krishnan A, Robertson AG, Bourke S, Doe S, Cummings SP, Anderson A, Forrest T, Griffin SM, Brodlie M, Pearson J, Ward C. Microbiological profiles of sputum and gastric juice aspirates in Cystic Fibrosis patients. Scientific Reports 2016, 6, 26985.
- Abdulkadir B, Nelson A, Skeath T, Marrs ECL, Perry JD, Cummings SP, Embleton ND, Berrington JE, Stewart CJ. Routine use of probiotics in preterm infants: longitudinal impact on the microbiome and metabolome. Neonatology 2016, 109(4), 239-247.
- Abdulkadir B, Nelson A, Skeath T, Marrs ECL, Perry JD, Cummings SP, Embleton ND, Berrington JE, Stewart CJ. Stool bacterial load in preterm infants with necrotising enterocolitis. Early Human Development 2016, 95, 1-2.
- Stewart CJ, Embleton ND, Marrs ECL, Smith DP, Nelson A, Abdulkadir B, Skeath T, Petrosino JF, Perry JD, Berrington JE, Cummings SP. Temporal bacterial and metabolic development of the preterm gut reveals specific signatures in health and disease. Microbiome 2016, 4, 67.
- Aagaard KJ, Stewart CJ, Chu D. Una destinatio, viae diversae: Does exposure to the vaginal microbiota confer health benefits to the infant, and does lack of exposure confer disease risk?. EMBO Reports 2016, 17(12), 1679-1684.
- Orr CH, Stewart CJ, Leifert C, Cooper JM, Cummings SP. Effect of crop management and sample year on abundance of soil bacterial communities in organic and conventional cropping systems. Journal of Applied Microbiology 2015, 119(1), 208-214.
- Stewart CJ, Cummings SP. Gut bacteria and necrotizing enterocolitis: cause or effect?. Trends in Microbiology 2015, 23(6), 332-333.
- Lane JP, Stewart CJ, Cummings SP, Gennery AR. Gut microbiome variations during hematopoietic stem cell transplant in severe combined immunodeficiency. Journal of Allergy and Clinical Immunology 2015, 135(6), 1654-1656.
- Stewart CJ, Skeath T, Nelson A, Fernstad SJ, Marrs ECL, Perry JD, Cummings SP, Berrington JE, Embleton ND. Preterm gut microbiota and metabolome following discharge from intensive care. Scientific Reports 2015, 5, 17141.
- Purcell P, Jary H, Perry A, Perry JD, Stewart CJ, Nelson A, Lanyon C, Smith DL, Cummings SP, De Soyza A. Polymicrobial airway bacterial communities in adult bronchiectasis patients. BMC Microbiology 2014, 14, 130.
- Berrington JE, Hearn RI, Hall C, Stewart CJ, Cummings SP, Embleton ND. Proportionate Reduction in Uncertainty of Late Onset Infection in Pre-term Infants by Neutrophil CD64 Measurement. Fetal & Pediatric Pathology 2014, 33(1), 16-22.
- Berrington JE, Stewart CJ, Cummings SP, Embleton ND. The neonatal bowel microbiome in health and infection. Current Opinion in Infectious Diseases 2014, 27(3), 236-243.
- Stewart CJ, Nelson A, Scribbins D, Marrs ECL, Lanyon C, Perry JD, Embleton ND, Cummings SP, Berrington JE. Bacterial and fungal viability in the preterm gut: NEC and sepsis. Archives of Disease in Childhood - Fetal and Neonatal Edition 2013, 98(4), F298-F303.
- Stewart CJ, Marrs ECL, Nelson A, Lanyon C, Perry JD, Embleton ND, Cummings SP, Berrington JE. Development of the Preterm Gut Microbiome in Twins at Risk of Necrotising Enterocolitis and Sepsis. PLoS ONE 2013, 8(8), e73465.
- Stewart CJ. Early Gut Microbiome and Polymicrobial infection. In: Nelson K, ed. Encyclopedia of Metagenomics. Berlin Heidelberg: SpringerReference, 2013.
- Berrington JE, Stewart CJ, Embleton ND, Cummings SP. Gut microbiota in preterm infants: assessment and relevance to health and disease. Archives of Disease in Childhood - Fetal and Neonatal Edition 2013, 98(4), F286-F290.
- Embleton ND, Berrington JE, McGuire W, Stewart CJ, Cummings SP. Lactoferrin: Antimicrobial activity and therapeutic potential. Seminars in Fetal and Neonatal Medicine 2013, 18(3), 143-149.
- Stewart CJ, Marrs ECL, Magorrian S, Nelson A, Lanyon C, Perry JD, Embleton ND, Cummings SP, Berrington JE. The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection. Acta Paediatrica 2012, 101(11), 1121-1127.