Training interdisciplinary glycoscientists to get a molecular-level grip on glycocodes at the human mucosa–microbiota interface

Project Information

SWEET CROSSTALK

Grant agreement ID: 814102

DOI

10.3030/814102

Project closed

EC signature date 30 August 2018

Start date 1 January 2019

End date 30 June 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 4 117 674,96

EU contribution

€ 4 117 674,96

Coordinated by

UNIVERSITEIT UTRECHT
Netherlands

Periodic Reporting for period 2 - SWEET CROSSTALK (Training interdisciplinary glycoscientists to get a molecular-level grip on glycocodes at the human mucosa–microbiota interface)

Reporting period: 2021-01-01 to 2023-06-30

Summary of the context and overall objectives of the project

Sweet Crosstalk, a European Training Network, focuses on the role of sugar molecules in the interaction between our gut and commensal bacteria, exploring implications for human health. This multidisciplinary network, consisting of 7 academic partners and 4 SME companies, merges excellence in fields like chemistry and microbiology, providing a holistic approach from fundamental insight to innovative applications. It has trained 15 Early Stage Researchers in interdisciplinary glycoscience and human microbiome research.
Humans coexist with mucosal microbiota, essential for health, aiding in nutrient synthesis and immune system modulation. Understanding the molecules driving microbiota–host interactions is crucial, with sugar molecules being pivotal in modulating these interactions. Sweet Crosstalk aims to unravel the role of these molecules, aspiring to develop “glycotechnologies” for improving human health through potential leads for novel diagnostics and therapeutics.
Concluded in June 2023, the project was segmented into three work packages, each focusing on different facets of glycoscience research. WP1 synthesized chemical probes for studying bacterial glycan utilization. WP2 provided insights crucial for developing novel therapeutic strategies by analyzing microbial cell envelope glycans. WP3 investigated the relationships between various glycans and their impacts on human health.
Despite challenges posed by the COVID-19 pandemic, the project facilitated the training of researchers and resulted in numerous scientific papers and presentations. In conclusion, Sweet Crosstalk has successfully advanced the understanding of glycans and their significant roles in human health and disease.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The Sweet Crosstalk ITN project, structured into three scientific work packages, aimed to explore the roles of glycans and glycoconjugates at the human mucosa–microbiota interface, focusing on their implications in human health and disease.
Workpackage 1 advanced understanding of host-microbiome interactions, particularly focusing on Ruminococcus gnavus and its implications on diseases like IBD. The researcher synthesized chemical probes to study bacterial glycan utilization and immune evasion mechanisms, conducted detailed studies on strain-level variations of Ruminococcus gnavus, and developed chemical tools to study microbiome enzymes involved in drug metabolism. The insights gained are crucial for developing novel therapeutic strategies and optimizing drug metabolism through microbiome modulation.
Workpackage 2 analyzed microbial cell envelope glycans and their interactions at the mucosa–microbiota interface. The researchers elucidated the chemical structures of lipopolysaccharides (LPS) from human microbiota bacteria, explored molecular interactions between human proteins and bacterial LPS, investigated the activity of enzymes processing sugars and glycans on the surface of pathogens, and employed computational methodologies to study glycosidase enzymes related to diseases. The methodologies and findings from these projects have broad applications, contributing to the advancement in understanding microbial interactions and developing future therapeutic interventions.
Workpackage 3 explored the relationships between mucosal, breast milk, and microbial glycans and their impacts on human health. The researchers focused on different aspects including the gut barrier, microbiota composition, immune system, gut-brain axis, inflammation, and metabolic disorders. It provided comprehensive insights into the multifaceted interactions between glycans and human health, emphasizing the importance of early life events and microbial interactions on the development of the immune system and overall health.
The project resulted in numerous scientific papers and presentations at international conferences. The trained researchers are now equipped to contribute significantly to academia, industry, or other fields in their future careers. In conclusion, the project successfully advanced the understanding of glycans and their interacting proteins, emphasizing their significant roles in human health and disease.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The Sweet Crosstalk ITN project, concluded in June 2023, has significantly advanced understanding of glycans and glycoconjugates at the human mucosa–microbiota interface, focusing on their implications in homeostasis, dysbiosis, human health, and disease.
Workpackage 1 has unraveled the dynamics and structures of human and bacterial glycans at the molecular level, focusing on interactions between host and Ruminococcus gnavus. Insights gained are crucial for understanding diseases like IBD and have provided leads for developing targeted antibacterial therapies through the study of bacterial glycan utilization and immune evasion mechanisms.
Workpackage 2 explored microbial cell envelope glycans, providing insights into the interaction between microbial glycans and the human immune system. The findings from this package have broad applications and contribute to understanding microbial interactions, potentially guiding the development of future therapeutic interventions.
Workpackage 3 provided insights into the interactions between glycans and human health, emphasizing the impact of early life events and microbial interactions on the development of the immune system, gut microbiota composition, and overall health. The findings could have implications for developing novel nutrition strategies to support health during infancy and later life.
The project has potential socio-economic impacts and wider societal implications. It is expected to catalyze the development of early diagnostics, nutraceuticals, glycotherapeutics, and “glycotechnologies,” improving human health through potential leads for novel diagnostics and therapeutics. The societal implications are crucial for developing novel therapeutic strategies and optimizing drug metabolism through microbiome modulation.
The project has also contributed to the training and development of 15 early-stage researchers, equipping them to make significant contributions to various fields in their future careers.
In conclusion, the project has made significant progress in understanding the roles of glycans and glycoconjugates, with potential impacts on society and the economy. The advancements are expected to provide novel insights and technologies that can improve human health and quality of life.

overview Sweet Crosstalk ITN