MSACL 2019 EU Abstract

Successful Faecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection Associates with Decreased Complexity of the Serum N-Glycome

Maja Pucic-Bakovic (1), Tanya M. Monaghan (2), Frano Vuckovic (1), Iwona Wojcik (1), Filip Klicek (1), Gordan Lauc (1,3), Dina Kao (4)
(1) Genos Glycoscience Research Laboratory, Zagreb, Croatia (2) NIHR Nottingham BRC and Nottingham Digestive Diseases Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, UK (3) Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia (4) Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada

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Maja Pučić Baković (Presenter) Genos Glycoscience Research Laboratory

Presenter Bio: Dr. Maja Pučić Baković joined Genos Ltd in 2008 and is currently a senior researcher mainly involved in method development, management of research within the EU and national funded projects, and communication with potential collaborators.
She graduated in Molecular Biology at the University of Zagreb in 2008, and gained a PhD in Biochemistry and Molecular Biology from the same University in 2013. From 2010 to 2012 she spent part of her doctoral training at the Center for Cancer Research and Development of the Rhode Island Hospital in Providence (USA), at the Leiden University Medical Center in Leiden (NL), and at BIA Separations Ltd (SLO). She received Collaborative Experimental Scholarship from FEBS in 2010, Young Scientist Award for 2011 from the Croatian Society of Biochemistry and Molecular Biology and the Best Publication Award for 2011 from the Croatian Immunological Society.

Relevant Financial Disclosures (within past 24 months) Salary Genos Ltd Discussing Products? YES, presenter will present educational content related to products/services of one or more ineligible company(ies) listed above. Conflict mitigation IN PROCESS.

INTRODUCTION: Glycosylation is complex and highly abundant posttranslational modification of proteins that significantly affects their structure and activity. Glycans are directly involved in pathophysiology of every major disease and show great potential as clinical disease markers.

AIM: The aim of this exploratory study was to examine for the first time whether composition of the total serum and IgG N-glycome changes in response to faecal microbiota transplantation (FMT) for recurrent C. difficile infection (rCDI).

METHODS: The study included samples from two separate prospective clinical trials. Discovery cohort comprised a total of 227 sera from 76 patients at screening, 4 and 12 weeks post-transplant, while replication cohort included 110 sera from 55 patients before and at one time point after FMT. Total serum N-glycans and IgG Fc N-glycopeptides were analysed by HILIC-UHPLC and nanoLC-ESI-MS, respectively. Linear mixed modelling was used for analysis of association between glycan traits and FMT treatment.

RESULTS: Serum N-glycome was found to be significantly changed following FMT. Meta-analysis identified a number of consistent changes indicating a reduction in the complexity of the serum N-glycome. Specifically, post FMT samples had a higher relative abundance of low-branching, monosialylated and digalactosylated glycans, and on the other hand a lower abundance of high-branching, tri- and tetragalactosylated, and tri- and tetrasialylated glycans.

CONCLUSION: These findings are contrary to those consistently reported in chronic inflammatory states, where a more complex serum N-glycome pattern predominates. Changes in the complexity of N-glycans in sera may be an important molecular mechanism by which FMT exerts its beneficial therapeutic effects in rCDI and could in part explain its success in IBD.