{"id":7687,"date":"2023-10-02T12:55:38","date_gmt":"2023-10-02T12:55:38","guid":{"rendered":"https:\/\/www.embl.org\/about\/info\/mmpu\/?page_id=7687"},"modified":"2026-03-23T09:27:32","modified_gmt":"2026-03-23T09:27:32","slug":"microbiota-drug-metabolism-and-cancer-therapy","status":"publish","type":"page","link":"https:\/\/www.embl.org\/about\/info\/mmpu\/research-groups\/microbiota-drug-metabolism-and-cancer-therapy\/","title":{"rendered":"Microbiota Drug Metabolism and Cancer Therapy"},"content":{"rendered":"\n<div class=\"vf-grid | vf-grid__col-3\"><div class=\"vf-grid__col--span-2\"><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<h2 class=\"wp-block-heading\">Group leaders: Michael Zimmermann, Matthias Ebert and Tianzuo Zhan <\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Our research interest<\/h3>\n\n\n\n<p>Anti-cancer drugs often show pronounced interpersonal variation in drug response, as well as dose- and treatment-limiting adverse effects. Accumulating evidence suggests that the intestinal microbiome and its capacity to metabolize drugs play an important role for these interpersonal differences. Therefore, the gut microbiota could serve as a biomarker and target to optimize cancer therapy and alleviate adverse effects.<\/p>\n\n\n\n<p>Our research collaboration combines expertise in clinical and translational oncology (Ebert, Zhan) with cutting-edge technologies for experimental microbiome studies (Zimmermann) to unravel the contribution of the gut microbiome to clinical responses to anti-cancer therapy.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Background<\/h3>\n\n\n\n<p>The human gut microbiota plays a vital role in human health and disease, by catabolizing food components and contributing to host metabolism. Recently, the gut microbiota was shown to actively metabolize therapeutic drugs, thereby affecting their availability and efficiency. Interpersonal variations in drug response and adverse-effects are a major challenge to personalized oncology. Currently, only few biomarkers are available that can predict therapy outcome for the majority of anti-neoplastic drug. The contribution of the gut microbiota to metabolism of anti-cancer drugs and their subsequent effects on therapy response in humans are poorly understood.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Goals<\/h3>\n\n\n\n<p>Our interdisciplinary collaboration will establish a novel pipeline to systematically quantify the impact of gut microbial metabolism of anti-cancer compounds on drug response and adverse effects. This will pave the ground to establish microbiome-encoded predictors of therapy response and toxicity, and uncover functional links between gut drug metabolism and tumor biology that may be therapeutically exploited.<\/p>\n\n\n\n<p>Our current and future goals are:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>to systematically characterize the capacity of gut microbes to metabolize anti-cancer drugs of clinical relevance<\/li>\n\n\n\n<li>link microbiota drug metabolism to the efficiency and adverse effects of anti-cancer drug therapies in patients<\/li>\n\n\n\n<li>mechanistically connect microbiota drug interactions to specific tumor phenotypes at the molecular level using a combination of microbiota and organoid culturing approaches.<\/li>\n<\/ul>\n\n\n\n<details  class=\"vf-details\" id=\"\"  >\n<summary class=\"vf-details--summary\">\nSelected publications<\/summary>\n<div class=\"acf-innerblocks-container\">\n\n<h4 class=\"wp-block-heading\"><strong>Ebert group:<\/strong><\/h4>\n\n\n\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40782795\/\">Combined MEK and PARP inhibition enhances radiation response in rectal cancer<\/a>.<br>Xiao Q, Riedesser JE, Mulholland T, Li Z, Buchloh J, Albrecht P, Yang X, Li M, Venkatachalam N, Skabkina O, Klupsch A, Eichhorn E, Wang L, Belle S, Schulte N, Schmitz D, Froelich MF, Trikhirhisthit K, Valentini E, Boonekamp KE, Petersen Y, Miersch T, Burgermeister E, Herskind C, Veldwijk MR, Brochhausen C, Ihnatko R, Krijgsveld J, Kurth I, Zhu Y, Ma Y, Cao K, Boutros M, Ebert MP, Zhan T, Betge J.<br>Cell Rep Med. 2025 Aug 19;6(8):102284. doi: 10.1016\/j.xcrm.2025.102284. Epub 2025 Aug 8.PMID: 40782795<\/p>\n\n\n\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39809756\/\">Digestive cancers: mechanisms, therapeutics and management.<\/a><br>Zhan T, Betge J, Schulte N, Dreikhausen L, Hirth M, Li M, Weidner P, Leipertz A, Teufel A, Ebert MP.<br>Signal Transduct Target Ther. 2025 Jan 15;10(1):24. doi: 10.1038\/s41392-024-02097-4.PMID: 39809756<\/p>\n\n\n\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/38719840\/\">Unveiling the culprit: the fusobacterium lineage that populates colorectal cancer.<\/a> <br>Betge J, Ebert MP.<br>Signal Transduct Target Ther. 2024 May 8;9(1):122. doi: 10.1038\/s41392-024-01844-x.PMID: 38719840<\/p>\n\n\n\n<p><a href=\"https:\/\/www.nature.com\/articles\/s44222-023-00072-2\">Engineering the gut microbiome<\/a><br>Bai X, Huang Z, Duraj-Thatte AM, Ebert MP, Zhang F, Burgermeister E, Liu X, Scott BM, Li G, Zuo T.<br>Nat Rev Bioeng 2023. doi.org\/10.1038\/s44222-023-00072-2<\/p>\n\n\n\n<p><a href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2666756822001167\">Second-line therapy with nivolumab plus ipilimumab for older patients with oesophageal squamous cell cancer (RAMONA): a multicentre, open-label phase 2 trial<\/a><br>Ebert MP, Meindl-Beinker N, Gutting T, Maenz M, Betge J, Schulte N, Zhan T, Weidner P, Burgermeister E, Hofheinz R, Vogel A, Angermeier S, Bolling C, de Wit M, Jakobs R, Karthaus M,&nbsp; Stocker G, Thuss-Patience P, Leidig T, Gaiser T, Kather JN, Haertel N. <br>Lancet Healthy Longev 2022;3:e417\u201327. doi: 10.1016\/S2666-7568(22)00116-7<\/p>\n\n\n\n<p><a href=\"https:\/\/www.nature.com\/articles\/s41467-022-30722-9\">The drug-induced phenotypic landscape of colorectal cancer organoids<\/a><br>Betge J, Rindtorff N, Sauer J, Rauscher B, Dingert C, Gaitantzi H, Herweck F, Srour-Mhanna K, Miersch T, Valentini E, Boonekamp KE, Hauber V, Gutting T, Frank L, Belle S, Gaiser T, Buchholz I, Jesenofsky R, H\u00e4rtel N, Zhan T, Fischer B, Breitkopf-Heinlein K, Burgermeister E, Ebert MP*, Boutros M*. <br>Nat Commun 2022;13:3135. doi: 10.1038\/s41467-022-30722-9<br>(*shared senior author)<\/p>\n\n\n\n<p><a href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0016508520305394\">CXCL10 and CCL21 Promote Migration of Pancreatic Cancer Cells Toward Sensory Neurons and Neural Remodeling in Tumors in Mice, Associated With Pain in Patients<\/a><br>Hirth M, Gandla J, H\u00f6per C, Gaida MM, Agarwal N, Simonetti M, Demir A, Xie Y, Weiss C, Michalski CW, Hackert T, Ebert MP, Kuner R. <br>Gastroenterology 2020;159:665-681. doi: 10.1053\/j.gastro.2020.04.037<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Zhan group<\/strong>:<\/h4>\n\n\n\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40782795\/\">Combined MEK and PARP inhibition enhances radiation response in rectal cancer.<\/a> <br>Xiao Q, Riedesser JE, Mulholland T, Li Z, Buchloh J, Albrecht P, Yang X, Li M, Venkatachalam N, Skabkina O, Klupsch A, Eichhorn E, Wang L, Belle S, Schulte N, Schmitz D, Froelich MF, Trikhirhisthit K, Valentini E, Boonekamp KE, Petersen Y, Miersch T, Burgermeister E, Herskind C, Veldwijk MR, Brochhausen C, Ihnatko R, Krijgsveld J, Kurth I, Zhu Y, Ma Y, Cao K, Boutros M, Ebert MP, Zhan T, Betge J.<br>Cell Rep Med. 2025 Aug 19;6(8):102284. doi: 10.1016\/j.xcrm.2025.102284. Epub 2025 Aug 8.PMID: 40782795<\/p>\n\n\n\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39809756\/\">Digestive cancers: mechanisms, therapeutics and management.<\/a><br>Zhan T, Betge J, Schulte N, Dreikhausen L, Hirth M, Li M, Weidner P, Leipertz A, Teufel A, Ebert MP.<br>Signal Transduct Target Ther. 2025 Jan 15;10(1):24. doi: 10.1038\/s41392-024-02097-4.PMID: 39809756<a href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.34155\"><\/a><\/p>\n\n\n\n<p><a href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.34155\">Targeting euchromatic histone lysine methyltransferases sensitizes colorectal cancer to histone deacetylase inhibitors<\/a><br>Bamberg LV, Heigwer F, Wandmacher AM, Singh A, Betge J, Rindtorff N, Werner J, Josten J, Skabkina OV, Hinsenkamp I, Erdmann G, R\u00f6cken C, Ebert MP, Burgermeister E, Zhan T+, Boutros M+. <br>Int J Cancer<em> <\/em>2022;151:1586\u20131601. doi:10.1002\/ijc.34155<\/p>\n\n\n\n<p><a href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.33393\">Multi\u2010omics integration identifies a selective vulnerability of colorectal cancer subtypes to YM155<\/a><br>Zhan T+, Faehling V+, Rauscher B+, Betge J, Ebert MP, Boutros M. <br>Int J Cancer 2021;148:1948\u20131963. doi:10.1002\/ijc.33393<\/p>\n\n\n\n<p><a href=\"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/1878-0261.12539\">Detection of mutational patterns in cell free DNA (cfDNA) of colorectal cancer by custom amplicon sequencing<\/a><br>Herrmann S+, Zhan T+, Betge J+, Rauscher B+, Belle S, Gutting T, Schulte N, Jesenofsky R, Haertel N, Gaiser T, Hofheinz RD, Ebert MP, Boutros M<em>.<\/em> <br>Mol Oncol 2019;13:1669\u20131683. doi:10.1002\/1878-0261.12539<\/p>\n\n\n\n<p><a href=\"https:\/\/www.nature.com\/articles\/s41467-019-09898-0\">MEK inhibitors activate Wnt signalling and induce stem cell plasticity in colorectal cancer<\/a><br>Zhan T+, Ambrosi G+, Wandmacher AM+, Rauscher B, Betge J, Rindtorff N, H\u00e4ussler R, Hinsenkamp I, Bamberg L, Hessling B, M\u00fcller-Decker K, Erdmann G, Burgermeister E, Ebert MP, Boutros M.<br>Nat Commun 2019;10:2197. doi:10.1038\/s41467-019-09898-0<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Zimmermann group<\/strong>:<\/h4>\n\n\n\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40890536\/\">ATF6 activation alters colonic lipid metabolism causing tumour-associated microbial adaptation.<\/a> <br>Coleman OI, Sorbie A, Riva A, von Stern M, Kuhls S, Selegato DM, Siegert L, Keidel I, K\u00f6hler N, Wirbel J, Kacprowski T, Dunkel A, Pauling JK, Plagge J, Mediel-Cuadra D, Wagner SJ, Chadly I, Bierwith S, Peng T, Metzler T, Li X, Heikenw\u00e4lder M, Schafmayer C, Hinz S, R\u00f6der C, R\u00f6cken C, Zimmermann M, Rosenstiel P, Steiger K, Jesinghaus M, Liebisch G, Ecker J, Schmidt C, Zeller G, Janssen KP, Haller D.<br>Nat Metab. 2025 Sep;7(9):1830-1850. doi: 10.1038\/s42255-025-01350-6. Epub 2025 Sep 1.PMID: 40890536<\/p>\n\n\n\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39321801\/\">Emergence of community behaviors in the gut microbiota upon drug treatment.<\/a><br>Garcia-Santamarina S, Kuhn M, Devendran S, Maier L, Driessen M, Mateus A, Mastrorilli E, Brochado AR, Savitski MM, Patil KR, Zimmermann M, Bork P, Typas A.<br>Cell. 2024 Sep 19:S0092-8674(24)00966-8. doi: 10.1016\/j.cell.2024.08.037. PMID: 39321801<\/p>\n\n\n\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39085612\/\">Gut microbiota carcinogen metabolism causes distal tissue tumours.<\/a><br>Roje B, Zhang B, Mastrorilli E, Kova\u010di\u0107 A, Su\u0161ak L, Ljubenkov I, \u0106osi\u0107 E, Vilovi\u0107 K, Me\u0161trovi\u0107 A, Vukovac EL, Bu\u010devi\u0107-Popovi\u0107 V, Puljiz \u017d, Karaman I, Terzi\u0107 J, Zimmermann M.<br>Nature. 2024 Jul 31. doi: 10.1038\/s41586-024-07754-w. PMID: 39085612<\/p>\n\n\n\n<p><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31158845\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31158845\/\" target=\"_blank\">Mapping human microbiome drug metabolism by gut bacteria and their genes<\/a><br>Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R, Goodman AL. <br>Nature 2019; 27;570(7762):462\u20137.<\/p>\n\n\n\n<p><a href=\"https:\/\/www.science.org\/doi\/10.1126\/science.aat9931\">Separating host and microbiome contributions to drug pharmacokinetics and toxicity<\/a><br>Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R, Goodman AL. <br>Science 2019; 8;363(6427). (doi:10.1126\/science.aat9931)<\/p>\n\n<\/div>\n<\/details>\n\n\n\n<details  class=\"vf-details\" id=\"group-members\"  >\n<summary class=\"vf-details--summary\">\nGroup members<\/summary>\n<div class=\"acf-innerblocks-container\">\n\n<p><strong>Lara B\u00fcchter <\/strong><br>MD student<br>Zhan Group, Department of Medicine II, Mannheim University Hospital<br>Phone: +49 621 383 1438<br><a href=\"mailto:xiaoxi.feng@stud.uni-heidelberg.de\"><\/a><a href=\"mailto:lara.buechter@stud.uni-heidelberg.de\">lara.buechter@stud.uni-heidelberg.de<\/a><\/p>\n\n\n\n<p><strong>Ayse Civana<\/strong><br>Study nurse<br>Ebert group, Department of Medicine II, Mannheim University Hospital<br>Phone: 0621 383 6674<br><a href=\"ayse.civana@medma.uni-heidelberg.de\">ayse.civana@medma.uni-heidelberg.de <\/a><\/p>\n\n\n\n<p><strong>Lena Dreikhausen, MD<\/strong><br>Clinician scientist<br>Zhan Group, Department of Medicine II, Mannheim University Hospital<br>Phone: 0621 383 1438<br><a href=\"mailto:lena.dreikhausen@umm.de\">lena.dreikhausen@umm.de<\/a><\/p>\n\n\n\n<p><strong>Xiaoxi Feng <\/strong><br>MD student<br>Zhan Group, Department of Medicine II, Mannheim University Hospital<br>Phone: +49 621 383 1438<br><a href=\"mailto:rabea.kindermann@stud.uni-heidelberg.de\"><\/a><a href=\"mailto:xiaoxi.feng@stud.uni-heidelberg.de\">xiaoxi.feng@stud.uni-heidelberg.de<\/a><\/p>\n\n\n\n<p><strong>Kaili Fu, PhD<\/strong><br>Postdoc<br>Zimmermann Group, EMBL, and Zhan Group, UMM<br>Phone: +49 (0)6221 387 8742<br><a href=\"mailto:matthias.gross@embl.de\"><\/a><a href=\"mailto:kaili.fu@embl.de\">kaili.fu@embl.de<\/a><\/p>\n\n\n\n<p><strong>Matthias Gross<\/strong><br>Research Technician<br>Zimmermann Group, EMBL<br>Phone: +49 (0)6221 387 8742<br><a href=\"mailto:matthias.gross@embl.de\">matthias.gross@embl.de<\/a><\/p>\n\n\n\n<p><strong>Rabea Kindermann<\/strong><br>MD student<br>Zhan Group, Department of Medicine II, Mannheim University Hospital<br>Phone: 0621 383 1438<br><a href=\"mailto:rabea.kindermann@stud.uni-heidelberg.de\">rabea.kindermann@stud.uni-heidelberg.de<\/a><\/p>\n\n\n\n<p><strong>Marie Pora <\/strong><br>PhD student<br>Zhan Group, Department of Medicine II, Mannheim University Hospital<br>Phone: 0621 383 1438<br><a href=\"mailto:marie.pora@stud.uni-heidelberg.de\">marie.pora@stud.uni-heidelberg.de<\/a>  <\/p>\n\n\n\n<p><strong>Jasmin Reinke, PhD<\/strong><br>Clinical trial coordinator<br>Ebert Group, Department of Medicine II, Mannheim University Hospital<br>Phone: 0621 383 4010<br><a href=\"mailto:jasmin.reinke@umm.de\">jasmin.reinke@umm.de<\/a><\/p>\n\n\n\n<p><strong>Janine Runke <\/strong><br>MD student<br>Zhan Group, Department of Medicine II, Mannheim University Hospital<br>Phone: 0621 383 1438<br><a href=\"mailto:rabea.kindermann@stud.uni-heidelberg.de\"><\/a><a href=\"mailto:janine.runke@stud.uni-heidelberg.de\">janine.runke@stud.uni-heidelberg.de<\/a> <\/p>\n\n\n\n<p><strong>Olga Skabkina, PhD<\/strong><br>Staff scientist<br>Zhan Group, Department of Medicine II, Mannheim University Hospital<br>Phone: 0621 383 1438<br><a href=\"mailto:olga.skabkina@medma.uni-heidelberg.de\">olga.skabkina@medma.uni-heidelberg.de<\/a><\/p>\n\n\n\n<p><strong>Fabian Springer<\/strong><br>PhD student (EMBL International PhD Programme \u2013 EIPP)<br>Zimmermann Group, EMBL<br>Phone: +49 6221 387 8140<br><a href=\"mailto:fabian.springer@embl.de\">fabian.springer@embl.de<\/a><\/p>\n\n<\/div>\n<\/details>\n\n\n\n<details  class=\"vf-details\" id=\"former-group-members\"  >\n<summary class=\"vf-details--summary\">\nFormer group members<\/summary>\n<div class=\"acf-innerblocks-container\">\n\n<p><strong>Ralf Jesenofsky, PhD<\/strong><br>Clinical trial coordinator<\/p>\n\n\n\n<p><strong>Qiyun Xiao<\/strong><br>MD\/PhD student, Zhan group<\/p>\n\n<\/div>\n<\/details>\n\n\n\n<div style=\"height:50px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n<\/div>\n<\/div>\n\n\n<div><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<article class=\"vf-card vf-card--brand vf-card--bordered vf-u-margin__bottom--800\" default>\n  \n  <div class=\"vf-card__content | vf-stack vf-stack--400\">\n          <h3 class=\"vf-card__heading\">\n        \n        On this page\n              <\/h3>\n    \n    \n          <p class=\"vf-card__text\"><ul>\r\n \t<li>Our research interest<\/li>\r\n \t<li>Background<\/li>\r\n \t<li>Goals<\/li>\r\n \t<li>Selected publications<\/li>\r\n \t<li>Group members<\/li>\r\n<\/ul><\/p>\n      <\/div>\n<\/article>\n\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":2,"featured_media":0,"parent":56,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"template-title-left-aligned.php","meta":{"_acf_changed":false,"footnotes":""},"embl_taxonomy":[],"class_list":["post-7687","page","type-page","status-publish","hentry"],"acf":[],"embl_taxonomy_terms":[],"_links":{"self":[{"href":"https:\/\/www.embl.org\/about\/info\/mmpu\/wp-json\/wp\/v2\/pages\/7687","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.embl.org\/about\/info\/mmpu\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.embl.org\/about\/info\/mmpu\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.embl.org\/about\/info\/mmpu\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.embl.org\/about\/info\/mmpu\/wp-json\/wp\/v2\/comments?post=7687"}],"version-history":[{"count":28,"href":"https:\/\/www.embl.org\/about\/info\/mmpu\/wp-json\/wp\/v2\/pages\/7687\/revisions"}],"predecessor-version":[{"id":17135,"href":"https:\/\/www.embl.org\/about\/info\/mmpu\/wp-json\/wp\/v2\/pages\/7687\/revisions\/17135"}],"up":[{"embeddable":true,"href":"https:\/\/www.embl.org\/about\/info\/mmpu\/wp-json\/wp\/v2\/pages\/56"}],"wp:attachment":[{"href":"https:\/\/www.embl.org\/about\/info\/mmpu\/wp-json\/wp\/v2\/media?parent=7687"}],"wp:term":[{"taxonomy":"embl_taxonomy","embeddable":true,"href":"https:\/\/www.embl.org\/about\/info\/mmpu\/wp-json\/wp\/v2\/embl_taxonomy?post=7687"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}