{"id":73263,"date":"2025-02-10T11:07:33","date_gmt":"2025-02-10T10:07:33","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=73263"},"modified":"2025-02-18T13:37:43","modified_gmt":"2025-02-18T12:37:43","slug":"bacteria-brains-and-sugar-scientists-uncover-new-connections","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science-technology\/bacteria-brains-and-sugar-scientists-uncover-new-connections\/","title":{"rendered":"Bacteria, brains, and sugar: scientists uncover new connections"},"content":{"rendered":"\n<article class=\"vf-card vf-card--brand vf-card--bordered vf-u-margin__bottom--800\" default>\n  <div class=\"vf-card__content | vf-stack vf-stack--400\">\n      <h3 class=\"vf-card__heading\">\n      Summary    <\/h3>\n                <p class=\"vf-card__text\"><ul>\r\n \t<li>Glycosylation is the process by which cells add sugar groups (also called carbohydrates) to proteins to modify their functions.<\/li>\r\n \t<li>EMBL researchers developed a new method to systematically and quantitatively study glycosylation and used it to show that gut bacteria can influence glycosylation patterns in the brains of mice.<\/li>\r\n \t<li>Using this method, the researchers could identify over 150,000 glycosylated forms of proteins (\u2018proteoforms&#8217;) in the brain, a more than 25-fold increase over previous studies.<\/li>\r\n \t<li>The study sheds new light on connections between the microbiome and the nervous system and provides a new method to study glycosylation&#8217;s role in fundamental biological processes.<\/li>\r\n<\/ul><\/p>\n      <\/div>\n<\/article>\n\n\n\n\n<p>Our guts are home to trillions of bacteria, and research over the last few decades has established how essential they are to our physiology \u2013 <a href=\"https:\/\/www.embl.org\/news\/tag\/microbiome\/#\">in health and disease<\/a>. A new study from EMBL Heidelberg researchers shows that gut bacteria can bring about profound molecular changes in one of our most critical organs \u2013 the brain.<\/p>\n\n\n\n<p>The new study, published in the journal <em>Nature Structural and Molecular Biology,<\/em> is the first to show that bacteria living in the gut can influence how proteins in the brain are modified by carbohydrates \u2013 a process called glycosylation. The study was made possible by a new method the scientists developed \u2013 DQGlyco \u2013 which allows them to study glycosylation at a much higher scale and resolution than previous studies.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><strong>A new way to measure glycosylation<\/strong><\/h2>\n\n\n\n<p>Proteins are the workhorses of our cells and their main building blocks. Sugars, or carbohydrates, on the other hand, are among the body&#8217;s main sources of energy. However, the cell also uses sugars to chemically modify proteins, altering their functions. This is called glycosylation.<\/p>\n\n\n\n<p>\u201cGlycosylation can affect how cells attach to each other (adhesion), how they move (motility), and even how they talk to one another (communication),\u201d explained Cl\u00e9ment Potel, first author of the study and Savitski Team Research Scientist. \u201cIt is involved in the pathogenesis of several diseases, including cancer and neuronal disorders.\u201d<\/p>\n\n\n\n<p>However, glycosylation has traditionally been notoriously difficult to study. Only a small portion of proteins in the cell are glycosylated and concentrating enough of them in a sample for studying (a process called \u2018enriching\u2019) tends to be laborious, expensive, and time-consuming.&nbsp;<\/p>\n\n\n\n<p>\u201cSo far, it&#8217;s not been possible to do such studies on a systematic scale, in a quantitative fashion, and with high reproducibility,\u201d said Mikhail Savitski, Team Leader, Senior Scientist, and Head of the Proteomics Core Facility at EMBL Heidelberg. \u201cThese are the challenges we managed to overcome with the new method.\u201d&nbsp;<\/p>\n\n\n\n<p>DQGlyco uses easily available and low-cost laboratory materials, such as functionalised silica beads, 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 could identify over 150,000 glycosylated forms of proteins (\u2018proteoforms&#8217;), an increase of over 25-fold compared to previous studies.<\/p>\n\n\n\n<p>The quantitative nature of the new method means that researchers can compare and measure differences between samples from different tissues, cell lines, species, etc. This also lets them study the pattern of &#8216;microheterogeneity\u2019 \u2013 the phenomenon where the same part of a protein can be modified by many (sometimes hundreds of) different sugar groups.&nbsp;<\/p>\n\n\n\n<p>One of the most common examples of microheterogeneity is human blood groups, where the presence of different sugar groups on proteins in red blood cells determines blood type (A, B, O, and AB). This plays a major role in deciding the success of blood transfusions from one individual to the other.&nbsp;<\/p>\n\n\n\n<p>The new method allowed the team to identify such microheterogeneity across hundreds of protein sites. \u201cI think the widespread prevalence of microheterogeneity is something people had always assumed but had never been clearly demonstrated, since you need to have enough coverage of glycosylated proteins to be able to make the statement,\u201d said Mira Burtscher, another first author of the study and a Savitski Team PhD student.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><strong>From the gut to the brain<\/strong><\/h2>\n\n\n\n<p>Given the method\u2019s precision and power, the researchers decided to use it to address an outstanding biological question. In collaboration with Michael Zimmerman&#8217;s group at EMBL, they next tested whether the gut microbiome had any effect on the glycosylation signatures they had observed in the brain. Both Zimmermann and Savitski are part of the <a href=\"https:\/\/www.embl.org\/about\/programme\/research-plans\/microbial-ecosystems\/\">Microbial Ecosystems Transversal Theme<\/a> at EMBL, which was introduced by the 2022-26 EMBL programme &#8216;Molecules to Ecosystems&#8217;.&nbsp;<\/p>\n\n\n\n<p>\u201cIt is known that gut microbiomes can affect neural functions, but the molecular details are largely unknown,\u201d said Potel. \u201cGlycosylation is implicated in many processes, such as neurotransmission and axon guidance, so we wanted to test if this was a mechanism by which gut bacteria influenced molecular pathways in the brain.\u201d<\/p>\n\n\n\n<p>Interestingly, the team found that when compared to &#8216;germ-free mice\u2019, i.e. mice grown in special environments such that they completely lack a gut microbiome, mice with different complements of gut bacteria had different glycosylation patterns in the brain. The changed patterns were particularly apparent in proteins known to be important in neural functions, such as cognitive processing and axon growth.&nbsp;<\/p>\n\n\n\n<p>The study\u2019s datasets are openly available via a new dedicated app for other researchers.\u00a0 In addition, the team is also curious whether the data can be used to inform predictions about glycosylation sites, especially in different species. For this, they have been using machine learning approaches such as AlphaFold \u2013 the AI-based tool for predicting protein structures recognised with the <a href=\"https:\/\/www.embl.org\/news\/science-technology\/alphafold-wins-nobel-prize-chemistry-2024\/\">2024 Nobel Prize in Chemistry<\/a>.\u00a0\u00a0<\/p>\n\n\n\n<p>\u201cBy training the models on mouse data, we can start predicting what could be the variability of glycosylation sites in humans, for example,\u201d said Martin Garrido, a postdoc in the Savitski and Saez-Rodriguez groups at EMBL and another first author of the study. \u201cIt could be very useful for people studying other organisms to help them identify glycosylation sites in their proteins of interest.\u201d<\/p>\n\n\n\n<p>The researchers are also working towards applying the new method to answer more fundamental biological questions and to understand the functional role glycosylation plays in cells.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Scientists have discovered that gut bacteria can alter molecular signatures in the brain, using a brand new method to study how carbohydrates modify proteins.<\/p>\n","protected":false},"author":124,"featured_media":73267,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[17591],"tags":[595,3634,5776,233,19459,45,434,882],"embl_taxonomy":[19371,19417],"class_list":["post-73263","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science-technology","tag-brain","tag-glycosylation","tag-microbial-ecosystems","tag-microbiome","tag-post-translational-modification","tag-proteomics","tag-savitski","tag-zimmermann","embl_taxonomy-savitski-team","embl_taxonomy-zimmermann-group"],"acf":{"vf_locked":false,"vfwp-news_embl_taxonomy":[19371,19417],"featured":true,"show_featured_image":false,"field_target_display":"embl","field_article_language":{"value":"english","label":"English"},"article_intro":"<p>Using a new method to study how carbohydrates modify proteins, scientists have discovered that gut bacteria can alter molecular signatures in the brain<\/p>\n","related_links":[{"link_description":"Savitski Team","link_url":"https:\/\/www.embl.org\/groups\/savitski\/"},{"link_description":"Zimmermann Group","link_url":"https:\/\/www.embl.org\/groups\/zimmermann\/"},{"link_description":"Molecular Systems Biology Unit","link_url":"https:\/\/www.embl.org\/research\/units\/molecular-systems-biology\/"},{"link_description":"Microbial Ecosystems Transversal Theme","link_url":"https:\/\/www.embl.org\/about\/programme\/research-plans\/microbial-ecosystems\/"}],"source_article":[{"publication_title":"Uncovering protein glycosylation dynamics and heterogeneity using deep quantitative glycoprofiling (DQGlyco)","publication_link":{"title":"","url":"https:\/\/www.nature.com\/articles\/s41594-025-01485-w","target":""},"publication_authors":"Potel C.M., Burtscher, M.L., Garrido-Rodriguez M. et al.","publication_source":"Nature Structural and Molecular Biology","publication_date":"10 February 2025","publication_doi":"10.1038\/s41594-025-01485-w"}],"in_this_article":false,"press_contact":"EMBL Generic","article_translations":false,"languages":""},"embl_taxonomy_terms":[{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"bd910dd7-0cda-4618-8bfa-d37fbda8438e\";i:2;s:36:\"b75f6f46-874c-40e5-a44f-a2bc5b173198\";}","parents":[],"name":["Savitski Team"],"slug":"savitski-team","description":"What &gt; Molecular Systems Biology &gt; Savitski Team"},{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"bd910dd7-0cda-4618-8bfa-d37fbda8438e\";i:2;s:36:\"5d13f823-c104-429b-836d-819ba78c22a9\";}","parents":[],"name":["Zimmermann Group"],"slug":"zimmermann-group","description":"What &gt; Molecular Systems Biology &gt; Zimmermann Group"}],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Bacteria, brains, and sugar: scientists uncover new connections | EMBL<\/title>\n<meta name=\"description\" content=\"Scientists have discovered that gut bacteria can alter molecular signatures in the brain, using a brand new method to study glycosylation.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.embl.org\/news\/science-technology\/bacteria-brains-and-sugar-scientists-uncover-new-connections\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Bacteria, brains, and sugar: scientists uncover new connections | EMBL\" \/>\n<meta property=\"og:description\" content=\"Scientists have discovered that gut bacteria can alter molecular signatures in the brain, using a brand new method to study glycosylation.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.embl.org\/news\/science-technology\/bacteria-brains-and-sugar-scientists-uncover-new-connections\/\" \/>\n<meta property=\"og:site_name\" content=\"EMBL\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/embl.org\/\" \/>\n<meta property=\"article:published_time\" content=\"2025-02-10T10:07:33+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2025-02-18T12:37:43+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2025\/02\/20250127_GutMicrobiome_gycosylationBrain_SavitskiGroup_FINAL.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"1000\" \/>\n\t<meta property=\"og:image:height\" content=\"600\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Shreya Ghosh\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@embl\" \/>\n<meta name=\"twitter:site\" content=\"@embl\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Shreya Ghosh\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"5 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"NewsArticle\",\"@id\":\"https:\/\/www.embl.org\/news\/science-technology\/bacteria-brains-and-sugar-scientists-uncover-new-connections\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/science-technology\/bacteria-brains-and-sugar-scientists-uncover-new-connections\/\"},\"author\":{\"name\":\"Shreya Ghosh\",\"@id\":\"https:\/\/www.embl.org\/news\/#\/schema\/person\/de071e57de42c03b5f23d1e391048fb2\"},\"headline\":\"Bacteria, brains, and sugar: scientists uncover new connections\",\"datePublished\":\"2025-02-10T10:07:33+00:00\",\"dateModified\":\"2025-02-18T12:37:43+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science-technology\/bacteria-brains-and-sugar-scientists-uncover-new-connections\/\"},\"wordCount\":902,\"publisher\":{\"@id\":\"https:\/\/www.embl.org\/news\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science-technology\/bacteria-brains-and-sugar-scientists-uncover-new-connections\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2025\/02\/20250127_GutMicrobiome_gycosylationBrain_SavitskiGroup_FINAL.jpg\",\"keywords\":[\"brain\",\"glycosylation\",\"microbial ecosystems\",\"microbiome\",\"post-translational modification\",\"proteomics\",\"savitski\",\"zimmermann\"],\"articleSection\":[\"Science &amp; 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