BY MARIA BURKE
A new study shows that gut bacteria can bring about molecular changes in the brain. It is the first to show that they can influence how carbohydrates modify proteins in the brain during a process called glycosylation. The study was made possible by a new method which allows researchers to study glycosylation at a much higher scale and resolution than previously.
Glycosylation can affect how cells attach to each other, how they move, and even how they communicate. It is involved in the pathogenesis of several diseases, including cancer and neuronal disorders. However, glycosylation has been difficult to study. Only a small portion of proteins in the cell are glycosylated, and concentrating enough of them in a sample to study (enriching) is laborious, expensive, and time-consuming.
However, the new method called DQGlyco uses easily available and low-cost materials to selectively enrich glycosylated proteins from biological samples, which can then be precisely identified and measured. Applying the method to brain tissue samples from mice, the researchers at EMBL Heidelberg identified over 150,000 glycosylated forms of proteins, 25 times more than previous studies.
The new method ‘allows studies on a systematic scale, in a quantitative fashion, and with high reproducibility,’ says Mikhail Savitski, team leader. It means that researchers can measure and compare differences between samples from different tissues, cell lines or species.
As glycosylation is implicated in many processes in the brain, the researchers decided to test if this was a mechanism by which gut bacteria influenced molecular pathways in the brain. The team found that when compared with mice grown in a sterile environment, mice colonised with different gut bacteria had different glycosylation patterns in the brain (Nature Structural & Molecular Biology, 2025, DOI: 10.1038/s41594-025-01485-w).
The changed patterns were particularly apparent in proteins known to be important in neural functions, such as cognitive processing and growth of axons, the part of neurons that transmit electrical impulses.
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