{"id":70437,"date":"2024-09-24T17:08:38","date_gmt":"2024-09-24T15:08:38","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=70437"},"modified":"2024-10-23T10:15:39","modified_gmt":"2024-10-23T08:15:39","slug":"better-together-gut-microbiome-communities-resilience-to-drugs","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science-technology\/better-together-gut-microbiome-communities-resilience-to-drugs\/","title":{"rendered":"Better together: gut microbiome communities\u2019 resilience to drugs"},"content":{"rendered":"\n\n\n\n\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 style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">Many common <\/span><a class=\"vf-card_link\" href=\"https:\/\/www.embl.org\/news\/science\/the-impact-of-drugs-on-gut-microbes-is-greater-than-we-thought\/\"><span style=\"font-weight: 400;\">drugs can impact<\/span><\/a><span style=\"font-weight: 400;\"> the composition of gut microbiome communities.<\/span><\/li>\r\n \t<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">EMBL scientists compared directly, for the first time, the effect of 30 diverse drug treatments on bacteria when they were grown in isolation versus as part of a complex community.<\/span><\/li>\r\n \t<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">The researchers found that the impact of drugs on bacteria is often less pronounced when they are part of a community, due to cross-protection strategies.\u00a0<\/span><\/li>\r\n \t<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">Mapping and understanding emergent drug-microbiome interactions within the community context may help scientists design improved therapies with fewer side effects and higher drug efficacy in the future.<\/span><\/li>\r\n<\/ul><\/p>\n      <\/div>\n<\/article>\n\n\n\n\n<p>Many human medications can directly inhibit the growth and alter the function of the bacteria that constitute our gut microbiome. EMBL Heidelberg researchers have now discovered that this effect is reduced when bacteria form communities.<\/p>\n\n\n\n<p>In a first-of-its-kind study, researchers from EMBL Heidelberg&#8217;s <a href=\"https:\/\/www.embl.org\/groups\/typas\/\">Typas<\/a>, <a href=\"https:\/\/www.embl.org\/groups\/bork\/\">Bork<\/a>, <a href=\"https:\/\/www.embl.org\/groups\/zimmermann\/\">Zimmermann<\/a>, and <a href=\"https:\/\/www.embl.org\/groups\/savitski\/\">Savitski<\/a> groups, and many EMBL alumni, including <a href=\"https:\/\/www.mrc-tox.cam.ac.uk\/staff\/kiran-patil\">Kiran Patil <\/a>(MRC Toxicology Unit Cambridge, UK), <a href=\"https:\/\/www.itqb.unl.pt\/research\/biology\/human-microbiota-xenobiotics-interactions\">Sarela Garcia-Santamarina<\/a> (ITQB, Portugal), <a href=\"https:\/\/www.umu.se\/en\/staff\/andre-mateus\/\">Andr\u00e9 Mateus<\/a> (Ume\u00e5 University, Sweden), as well as <a href=\"https:\/\/www.medizin.uni-tuebingen.de\/de\/das-klinikum\/mitarbeiter\/profil\/2110\">Lisa Maier<\/a> and <a href=\"https:\/\/www.cmfi.uni-tuebingen.de\/en\/research\/junior-research-groups\/brochado-lab\">Ana Rita Brochado<\/a> (University T\u00fcbingen, Germany), compared a large number of drug-microbiome interactions between bacteria grown in isolation and those part of a complex microbial community. Their findings were recently published in the journal <em><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0092867424009668?via%3Dihub\">Cell<\/a><\/em>.<\/p>\n\n\n\n<p>For their study, the team investigated how 30 different drugs (including those targeting infectious or noninfectious diseases) affect 32 different bacterial species. These 32 species were chosen as representative of the human gut microbiome based on data available across five continents.&nbsp;<\/p>\n\n\n\n<p>They found that when together, certain drug-resistant bacteria display communal behaviours that protect other bacteria that are sensitive to drugs. This &#8216;cross-protection&#8217; behaviour allows such sensitive bacteria to grow normally when in a community in the presence of drugs that would have killed them if they were isolated.&nbsp;<\/p>\n\n\n\n<p>\u201cWe were not expecting so much resilience,\u201d said Sarela Garcia-Santamarina, a former postdoc in the Typas group and co-first author of the study, currently a group leader in the <a href=\"https:\/\/www.itqb.unl.pt\/\">Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica (ITQB)<\/a>, Universidade Nova de Lisboa, Portugal. \u201cIt was very surprising to see that in up to half of the cases where a bacterial species was affected by the drug when grown alone, it remained unaffected in the community.\u201d&nbsp;<\/p>\n\n\n\n<p>The researchers then dug deeper into the molecular mechanisms that underlie this cross-protection. \u201cThe bacteria help each other by taking up or breaking down the drugs,\u201d explained Michael Kuhn, Research Staff Scientist in the Bork Group and a co-first author of the study. &#8220;These strategies are called bioaccumulation and biotransformation respectively.&#8221;&nbsp;<\/p>\n\n\n\n<p>\u201cThese findings show that gut bacteria have a larger potential to transform and accumulate medicinal drugs than previously thought,\u201d said Michael Zimmermann, Group Leader at EMBL Heidelberg and one of the study collaborators.&nbsp;<\/p>\n\n\n\n<p>However, there is also a limit to this community strength. The researchers saw that high drug concentrations cause microbiome communities to collapse and the cross-protection strategies to be replaced by &#8216;cross-sensitisation&#8217;. In cross-sensitisation, bacteria which would normally be resistant to certain drugs become sensitive to them when in a community \u2013 the opposite of what the authors saw happening at lower drug concentrations.&nbsp;<\/p>\n\n\n\n<blockquote class=\"vf-blockquote | vf-u-margin__bottom--600 vf-u-margin__top--600\">\n  <div>\n    <div>\n      \u201cThis means that the community composition stays robust at low drug concentrations, as individual community members can protect sensitive species. But, when the drug concentration increases, the situation reverses. Not only do more species become sensitive to the drug and the capacity for cross-protection drops, but also negative interactions emerge, which sensitise further community members. We are interested in understanding the nature of these cross-sensitisation mechanisms in the future.\u201d    <\/div>\n    \n          <footer class=\"vf-u-margin__top--600\">\n      \n      <div class=\"vf-blockquote_author\">\n        \u2013 Nassos Typas, EMBL group leader and senior author of the study      <\/div>\n\n      \n      <div class=\"vf-blockquote_author__details\"><\/div>\n    <\/footer>\n      <\/div>\n<\/blockquote>\n\n\n\n<p>Just like the bacteria they studied, the researchers also took a community strategy for this study, combining their scientific strengths. The Typas Group are experts in high-throughput experimental microbiome and microbiology approaches, while the Bork Group contributed with their expertise in bioinformatics, the Zimmermann Group did metabolomics studies, and the Savitski Group did the proteomics experiments. Among external collaborators, EMBL alumnus Kiran Patil&#8217;s group at <a href=\"https:\/\/www.mrc-tox.cam.ac.uk\/\">Medical Research Council Toxicology Unit<\/a>, University of Cambridge, United Kingdom, provided expertise in gut bacterial interactions and microbial ecology.&nbsp;<\/p>\n\n\n\n<p>As a forward-looking experiment, authors also used this new knowledge of cross-protection interactions to assemble synthetic communities that could keep their composition intact upon drug treatment.&nbsp;&nbsp;<\/p>\n\n\n\n<p>\u201cThis study is a stepping stone towards understanding how medications affect our gut microbiome. In the future, we might be able to use this knowledge to tailor prescriptions to reduce drug side effects,&#8221; said Peer Bork, Group Leader and Director at EMBL Heidelberg. \u201cTowards this goal, we are also studying how interspecies interactions are shaped by nutrients so that we can create even better models for understanding the interactions between bacteria, drugs, and the human host,\u201d added Patil.&nbsp;<\/p>\n\n\n\n<div style=\"height:10px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<hr class=\"vf-divider\"\/>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"spanish\"><strong>La uni\u00f3n hace la fuerza: la resistencia de las comunidades de la microbiota intestinal a los medicamentos<\/strong><\/h2>\n\n\n<div class=\"vf-section-header | vf-u-margin__bottom--400\">\n  <h2 class=\"vf-section-header__heading\">\n  Las bacterias sensibles a los medicamentos pueden volverse m\u00e1s resistentes cuando forman parte de comunidades, gracias a estrategias de protecci\u00f3n cruzada.  <\/h2>\n  <\/div>\n\n\n\n\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      Resumen     <\/h3>\n                <p class=\"vf-card__text\"><ul>\r\n \t<li>Muchos <a class=\"vf-card_link\" href=\"https:\/\/www.embl.org\/news\/science\/the-impact-of-drugs-on-gut-microbes-is-greater-than-we-thought\/\">medicamentos comunes pueden afectar<\/a> la composici\u00f3n de las comunidades de la microbiota intestinal.<\/li>\r\n \t<li>Cient\u00edficos del EMBL compararon directamente, por primera vez, el efecto de 30 tratamientos farmacol\u00f3gicos diferentes en bacterias cultivadas de forma aislada y bacterias que forman parte de una comunidad compleja de bacterias.<\/li>\r\n \t<li>Los investigadores descubrieron que el impacto de los medicamentos en las bacterias es a menudo menos notable cuando forman parte de una comunidad, debido a las estrategias de protecci\u00f3n cruzada.<\/li>\r\n \t<li>Mapear y comprender las interacciones emergentes entre medicamentos y la microbiota en el contexto de la comunidad podr\u00eda ayudar a los cient\u00edficos a dise\u00f1ar terapias mejoradas con menos efectos secundarios y una mayor eficacia.<\/li>\r\n<\/ul><\/p>\n      <\/div>\n<\/article>\n\n\n\n\n<p>Muchos medicamentos pueden inhibir directamente el crecimiento y alterar la funci\u00f3n de las bacterias que forman nuestra microbiota intestinal. Investigadores del EMBL en Heidelberg han descubierto que los efectos de algunos medicamentos se reducen cuando las bacterias forman comunidades.<\/p>\n\n\n\n<p>En un estudio pionero, investigadores de los grupos de investigaci\u00f3n <a href=\"https:\/\/www.embl.org\/groups\/typas\/\">Typas<\/a>, <a href=\"https:\/\/www.embl.org\/groups\/bork\/\">Bork<\/a>, <a href=\"https:\/\/www.embl.org\/groups\/zimmermann\/\">Zimmermann<\/a> y <a href=\"https:\/\/www.embl.org\/groups\/savitski\/\">Savitski<\/a> de EMBL Heidelberg, junto con muchos ex-compa\u00f1eros de EMBL, incluyendo a <a href=\"https:\/\/www.mrc-tox.cam.ac.uk\/staff\/kiran-patil\">Kiran Patil<\/a> (Unidad de Toxicolog\u00eda del MRC en Cambridge, Reino Unido), <a href=\"https:\/\/www.itqb.unl.pt\/research\/biology\/human-microbiota-xenobiotics-interactions\">Sarela Garcia-Santamarina<\/a> (ITQB, Portugal), <a href=\"https:\/\/www.umu.se\/en\/staff\/andre-mateus\/\">Andr\u00e9 Mateus<\/a> (Universidad de Ume\u00e5, Suecia), as\u00ed como <a href=\"https:\/\/www.medizin.uni-tuebingen.de\/de\/das-klinikum\/mitarbeiter\/profil\/2110\">Lisa Maier<\/a> y <a href=\"https:\/\/www.cmfi.uni-tuebingen.de\/en\/research\/junior-research-groups\/brochado-lab\">Ana Rita Brochado<\/a> (Universidad de T\u00fcbingen, Alemania), compararon un gran n\u00famero de interacciones entre medicamentos y microbiota, tanto en bacterias cultivadas de forma aislada como en aquellas que formaban parte de una comunidad microbiana compleja. Sus hallazgos han sido publicados en la revista <em><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0092867424009668?via%3Dihub\">Cell<\/a><\/em>.<\/p>\n\n\n\n<p>Para su estudio, el equipo investig\u00f3 c\u00f3mo 30 medicamentos diferentes (incluyendo aquellos dirigidos a enfermedades infecciosas y no infecciosas) afectan a 32 especies bacterianas distintas. Estas 32 especies fueron elegidas como representativas de la microbiota intestinal humana, bas\u00e1ndose en datos disponibles de los cinco continentes.<\/p>\n\n\n\n<p>Descubrieron que, cuando estaban juntas, ciertas bacterias resistentes a los medicamentos mostraban comportamientos comunales que proteg\u00edan a otras bacterias sensibles a los f\u00e1rmacos. Este comportamiento de &#8216;protecci\u00f3n cruzada&#8217; permit\u00eda a estas bacterias sensibles crecer de manera normal en una comunidad, a pesar de la presencia de medicamentos que las habr\u00edan matado si estuvieran aisladas.<\/p>\n\n\n\n<p>\u201cNo esper\u00e1bamos tanta resistencia\u201d, apunta Sarela Garcia-Santamarina, ex postdoctoranda del grupo de Typas y coautora principal del estudio, actualmente jefa de grupo en el <a href=\"https:\/\/www.itqb.unl.pt\/\">Instituto de Tecnolog\u00eda Qu\u00edmica y Biol\u00f3gica<\/a> (ITQB), Universidade Nova de Lisboa, Portugal. \u201cFue muy sorprendente ver que, en hasta la mitad de los casos en los que una especie bacteriana era afectada por el medicamento cuando crec\u00eda sola, no se ve\u00eda afectada en la comunidad\u201d.<\/p>\n\n\n\n<p>Los investigadores profundizaron entonces en los mecanismos moleculares que subyacen a esta protecci\u00f3n cruzada. \u201cLas bacterias se ayudan entre s\u00ed al absorber o descomponer los medicamentos\u201d, explica Michael Kuhn, cient\u00edfico del Grupo Bork y coautor principal del estudio. &#8220;Estas estrategias se llaman bioacumulaci\u00f3n y biotransformaci\u00f3n, respectivamente&#8221;.<\/p>\n\n\n\n<p>\u201cEstos hallazgos muestran que las bacterias intestinales tienen un mayor potencial para transformar y acumular medicamentos de lo que se pensaba previamente\u201d, dijo Michael Zimmermann, jefe de grupo en EMBL Heidelberg y uno de los colaboradores del estudio.<\/p>\n\n\n\n<p>Sin embargo, tambi\u00e9n hay un l\u00edmite en la fortaleza de la comunidad. Los investigadores observaron que las concentraciones altas de medicamentos hacen que las comunidades de la microbiota colapsen, y que las estrategias de protecci\u00f3n cruzada sean reemplazadas por &#8216;sensibilizaci\u00f3n cruzada&#8217;. En la sensibilizaci\u00f3n cruzada, las bacterias que normalmente ser\u00edan resistentes a ciertos medicamentos se vuelven sensibles a ellos cuando est\u00e1n en una comunidad, lo contrario de lo que los autores observaron en concentraciones m\u00e1s bajas de medicamentos.<\/p>\n\n\n\n<p>\u201cEsto significa que la composici\u00f3n de la comunidad se mantiene robusta a bajas concentraciones de medicamentos, ya que los miembros individuales de la comunidad pueden proteger a las especies sensibles&#8221;, a\u00f1ade Nassos Typas, jefe de grupo en EMBL y autor principal del estudio. &#8220;Pero, cuando la concentraci\u00f3n del medicamento aumenta, la situaci\u00f3n se invierte. No solo m\u00e1s especies se vuelven sensibles al f\u00e1rmaco y la capacidad de protecci\u00f3n cruzada disminuye, sino que tambi\u00e9n emergen interacciones negativas que sensibilizan a m\u00e1s miembros de la comunidad. Para futuros proyectos, estamos interesados en comprender la naturaleza de estos mecanismos de sensibilizaci\u00f3n cruzada\u201d.<\/p>\n\n\n\n<p>Al igual que las bacterias que estudiaron, los investigadores tambi\u00e9n adoptaron una estrategia comunitaria para este estudio, combinando sus fortalezas cient\u00edficas. El grupo de Typas es experto en enfoques experimentales de alto rendimiento para la microbiota y la microbiolog\u00eda, mientras que el Grupo Bork contribuy\u00f3 con su experiencia en bioinform\u00e1tica, el Grupo Zimmermann realiz\u00f3 estudios de metabol\u00f3mica y el Grupo Savitski llev\u00f3 a cabo los experimentos de prote\u00f3mica. Entre los colaboradores externos, el grupo del ex compa\u00f1ero de EMBL Kiran Patil en la <a href=\"https:\/\/www.mrc-tox.cam.ac.uk\/\">Unidad de Toxicolog\u00eda del Consejo de Investigaci\u00f3n M\u00e9dica (MRC)<\/a>, Universidad de Cambridge, Reino Unido, aport\u00f3 su experiencia en interacciones bacterianas intestinales y ecolog\u00eda microbiana.<\/p>\n\n\n\n<p>Como un experimento prospectivo, los autores tambi\u00e9n utilizaron este nuevo conocimiento sobre las interacciones de protecci\u00f3n cruzada para ensamblar comunidades sint\u00e9ticas que pudieran mantener su composici\u00f3n intacta ante el tratamiento con medicamentos.<\/p>\n\n\n\n<p>\u201cEste estudio es un paso importante para entender c\u00f3mo los medicamentos afectan a nuestra microbiota intestinal. En el futuro, podr\u00edamos utilizar este conocimiento para ajustar las prescripciones m\u00e9dicas y reducir los efectos secundarios de los f\u00e1rmacos&#8221;, comenta Peer Bork, jefe de grupo y director de EMBL Heidelberg. &#8220;Con este objetivo en mente, tambi\u00e9n estamos estudiando c\u00f3mo las interacciones entre especies son moldeadas por los nutrientes para poder crear modelos a\u00fan mejores que nos permitan comprender las interacciones entre las bacterias, los medicamentos y el hu\u00e9sped humano&#8221;, agrega Patil.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"german\"><strong>Gemeinsam besser: Resistenz von Darm-Mikrobiom-Gemeinschaften gegen Medikamente<\/strong><\/h2>\n\n\n\n<p>Bakterien, die empfindlich auf Medikamente reagieren, k\u00f6nnen als Teil von Gemeinschaften durch Kreuzabwehrstrategien widerstandsf\u00e4higer werden<\/p>\n\n\n\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      Zusammenfassung    <\/h3>\n                <p class=\"vf-card__text\"><ul>\r\n \t<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">Viele g\u00e4ngige <a class=\"vf-card_link\" href=\"https:\/\/www.embl.org\/news\/science\/the-impact-of-drugs-on-gut-microbes-is-greater-than-we-thought\/\">Medikamente k\u00f6nnen die Zusammensetzung der Mikrobiom-Gemeinschaften<\/a> im Darm beeinflussen.<\/span><\/li>\r\n \t<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">Wissenschaftlerinnen und Wissenschaftler des EMBL haben zum ersten Mal die Wirkung von 30 verschiedenen Medikamenten auf Bakterien direkt verglichen, wenn diese isoliert oder als Teil einer komplexen Gemeinschaft kultiviert wurden.<\/span><\/li>\r\n \t<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">Die Forschenden fanden heraus, dass die Wirkung von Medikamenten auf Bakterien oft weniger ausgepr\u00e4gt ist, wenn sie Teil einer Gemeinschaft sind, was auf gegenseitige Schutzstrategien zur\u00fcckzuf\u00fchren ist.<\/span><\/li>\r\n \t<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">Die Kartierung und das Verst\u00e4ndnis der sich entwickelnden Wechselwirkungen zwischen Medikamenten und dem Mikrobiom im Kontext der Gemeinschaft k\u00f6nnen Wissenschaftlerinnen und Wissenschaftler helfen, in Zukunft bessere Therapien mit weniger Nebenwirkungen und h\u00f6herer Wirksamkeit zu entwickeln.<\/span><\/li>\r\n<\/ul><\/p>\n      <\/div>\n<\/article>\n\n\n\n\n<p>Viele Humanarzneimittel k\u00f6nnen das Wachstum und die Funktion von Bakterien, die unser Darmmikrobiom bilden, direkt hemmen. Forschende des EMBL Heidelberg haben nun herausgefunden, dass dieser Effekt abgeschw\u00e4cht wird, wenn Bakterien Gemeinschaften bilden.<\/p>\n\n\n\n<p>In einer erstmals durchgef\u00fchrten Studie verglichen Forschende aus den Gruppen <a href=\"https:\/\/www.embl.org\/groups\/typas\/\">Typas<\/a>, <a href=\"https:\/\/www.embl.org\/groups\/bork\/\">Bork<\/a>, <a href=\"https:\/\/www.embl.org\/groups\/zimmermann\/\">Zimmermann<\/a> und <a href=\"https:\/\/www.embl.org\/groups\/savitski\/\">Savitski<\/a> am EMBL Heidelberg eine Vielzahl von Arzneimittel-Mikrobiom-Wechselwirkungen zwischen isoliert kultivierten Bakterien und solchen, die Teil einer komplexen mikrobiellen Gemeinschaft sind. Zahlreiche ehemalige EMBL-Forschende, darunter <a href=\"https:\/\/www.mrc-tox.cam.ac.uk\/staff\/kiran-patil\">Kiran Patil <\/a>(MRC Toxicology Unit Cambridge, Gro\u00dfbritannien), <a href=\"https:\/\/www.itqb.unl.pt\/research\/biology\/human-microbiota-xenobiotics-interactions\">Sarela Garcia-Santamarina<\/a> (ITQB, Portugal) und <a href=\"https:\/\/www.umu.se\/en\/staff\/andre-mateus\/\">Andr\u00e9 Mateus<\/a> (Universit\u00e4t Ume\u00e5, Schweden) sowie <a href=\"https:\/\/www.medizin.uni-tuebingen.de\/de\/das-klinikum\/mitarbeiter\/profil\/2110\">Lisa Maier<\/a> und <a href=\"https:\/\/www.cmfi.uni-tuebingen.de\/en\/research\/junior-research-groups\/brochado-lab\">Ana Rita Brochado<\/a> (Universit\u00e4t T\u00fcbingen, Deutschland) erg\u00e4nzten die Studie mit ihrer Expertise. Die Ergebnisse wurden k\u00fcrzlich in der Fachzeitschrift <a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0092867424009668?via%3Dihub\">Cell<\/a> ver\u00f6ffentlicht.<\/p>\n\n\n\n<p>F\u00fcr ihre Studie untersuchte das Team, wie 30 verschiedene Medikamente (darunter Arzneimittel gegen infekti\u00f6se und nicht-infekti\u00f6se Krankheiten) auf 32 verschiedene Bakterienarten wirken. Diese 32 Arten wurden auf der Grundlage von Daten aus f\u00fcnf Kontinenten als repr\u00e4sentativ f\u00fcr das menschliche Darmmikrobiom ausgew\u00e4hlt.<\/p>\n\n\n\n<p>Die Forschenden fanden heraus, dass bestimmte arzneimittelresistente Bakterien gemeinsam ein Verhalten aufweisen, das andere arzneimittelresistente Bakterien sch\u00fctzt. Dieses \u201ekreuzprotektive\u201c Verhalten erm\u00f6glicht es den empfindlichen Bakterien, normal weiter zu wachsen wenn sie sich in einer Gemeinschaft befinden, w\u00e4hrend sie isoliert absterben w\u00fcrden.&nbsp;<\/p>\n\n\n\n<p>\u201eWir hatten nicht erwartet, dass die Bakterien so resistent sein w\u00fcrden\u201c, sagt Sarela Garcia-Santamarina, ehemalige Postdoktorandin in der Typas-Gruppe, Mitautorin der Studie und jetzt Gruppenleiterin am <a href=\"https:\/\/www.itqb.unl.pt\/\">Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica<\/a> (ITQB) der Universidade Nova de Lisboa in Portugal. \u201eEs war sehr \u00fcberraschend zu beobachten, dass in bis zur H\u00e4lfte der F\u00e4lle, in denen eine Bakterienart durch das Medikament beeintr\u00e4chtigt wurde, wenn sie allein kultiviert wurde, sie in der Gemeinschaft unbeeinflusst blieb\u201c.<\/p>\n\n\n\n<p>Die Forschenden untersuchten daraufhin die molekularen Mechanismen, die diesem gegenseitigen Schutz zugrunde liegen. \u201eDie Bakterien helfen sich gegenseitig, indem sie die Medikamente aufnehmen oder abbauen\u201c, erkl\u00e4rt Michael Kuhn, wissenschaftlicher Mitarbeiter in Borks Gruppe und Mitautor der Studie. &#8220;Diese Strategien nennt man Bioakkumulation oder Biotransformation.\u201d<\/p>\n\n\n\n<p>\u201eDie Ergebnisse zeigen, dass Darmbakterien ein gr\u00f6\u00dferes Potenzial zur Umwandlung und Anreicherung von Medikamenten haben als bisher angenommen\u201c, sagt Michael Zimmermann, Gruppenleiter am EMBL Heidelberg und einer der Autoren der Studie.<\/p>\n\n\n\n<p>Allerdings gibt es auch eine Grenze f\u00fcr die St\u00e4rke dieser Gemeinschaft. Die Forschenden fanden heraus, dass hohe Arzneimittelkonzentrationen dazu f\u00fchren, dass die Mikrobiom-Gemeinschaften zusammenbrechen und die Kreuzschutzstrategien durch eine \u201eKreuzsensibilisierung\u201c ersetzt werden. Bei der Kreuzsensibilisierung werden Bakterien, die normalerweise gegen bestimmte Medikamente resistent sind, in einer Gemeinschaft empfindlich gegen\u00fcber diesen Medikamenten &#8211; genau das Gegenteil von dem, was die Autoren bei niedrigeren Medikamentenkonzentrationen beobachtet haben.<\/p>\n\n\n\n<p>\u201eDas bedeutet, dass die Zusammensetzung der Gemeinschaft bei niedrigen Medikamentenkonzentrationen stabil bleibt, da einzelne Mitglieder der Gemeinschaft empfindliche Arten sch\u00fctzen k\u00f6nnen\u201c, erkl\u00e4rt Nassos Typas, Gruppenleiter am EMBL und Hauptautor der Studie. \u201eSteigt jedoch die Konzentration der Medikamente, kehrt sich die Situation um. Dann werden nicht nur mehrere Arten empfindlich und die F\u00e4higkeit, sich gegenseitig zu sch\u00fctzen, nimmt ab. Sondern es kommt auch zu negativen Wechselwirkungen, die weitere Mitglieder der Gemeinschaft sensibilisieren. Als n\u00e4chstes wollen wir untersuchen, wie die Kreuz-Sensibilisierungsmechanismen funktionieren.\u201d<\/p>\n\n\n\n<p>Wie bei den untersuchten Bakterien w\u00e4hlten die Forschenden auch bei dieser Studie einen gemeinschaftlichen Ansatz und b\u00fcndelten ihre wissenschaftlichen St\u00e4rken. Die Typas-Gruppe ist Expertin f\u00fcr experimentelle Hochdurchsatz-Mikrobiom- und Mikrobiologie-Ans\u00e4tze, die Bork-Gruppe steuerte ihre Bioinformatik-Expertise bei, die Zimmermann-Gruppe f\u00fchrte Metabolomics-Studien durch und die Savitski-Gruppe die Proteomics-Experimente. Zu den externen Mitarbeitenden geh\u00f6rte auch die Gruppe des EMBL-Alumnus Kiran Patil von der <a href=\"https:\/\/www.mrc-tox.cam.ac.uk\/\">Medical Research Council Toxicology Unit<\/a> der Universit\u00e4t Cambridge in Gro\u00dfbritannien, die ihr Fachwissen \u00fcber bakterielle Interaktionen im Darm und mikrobielle \u00d6kologie einbrachte.<\/p>\n\n\n\n<p>In einem zukunftsweisenden Experiment nutzten die Autoren die neuen Erkenntnisse \u00fcber die Wechselwirkungen zwischen den Schutzmechanismen auch, um synthetische Gemeinschaften zusammenzustellen, die ihre Zusammensetzung w\u00e4hrend einer Behandlung mit Medikamenten beibehalten k\u00f6nnen.&nbsp;<\/p>\n\n\n\n<p>\u201eDiese Studie ist ein Meilenstein auf dem Weg zum Verst\u00e4ndnis, wie Medikamente unser Darmmikrobiom beeinflussen. In Zukunft k\u00f6nnten wir dieses Wissen nutzen, um Medikamente so zu verschreiben, dass sie weniger Nebenwirkungen haben\u201c, sagt Peer Bork, Gruppenleiter und Direktor am EMBL Heidelberg. \u201eUm dieses Ziel zu erreichen, untersuchen wir auch, wie die Interaktionen zwischen den Arten durch N\u00e4hrstoffe beeinflusst werden, so dass wir noch bessere Modelle f\u00fcr das Verst\u00e4ndnis der Wechselwirkungen zwischen Bakterien, Medikamenten und dem menschlichen Wirt schaffen k\u00f6nnen\u201c, f\u00fcgt Patil hinzu.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"portugu\u00eas\"><strong>A uni\u00e3o faz a for\u00e7a: resist\u00eancia de comunidades na microbiota intestinal a medicamentos<\/strong><\/h2>\n\n\n\n<p>Bact\u00e9rias que s\u00e3o sens\u00edveis a medicamentos podem tornar-se resistentes quando fazem parte de comunidades, atrav\u00e9s de estrat\u00e9gias de coprote\u00e7\u00e3o<\/p>\n\n\n\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      Sum\u00e1rio    <\/h3>\n                <p class=\"vf-card__text\"><ul>\r\n \t<li>Muitos <a class=\"vf-card_link\" href=\"https:\/\/www.embl.org\/news\/science\/the-impact-of-drugs-on-gut-microbes-is-greater-than-we-thought\/\">medicamentos comuns podem afetar a composi\u00e7\u00e3o das comunidades microbiotas<\/a> no intestino.<\/li>\r\n \t<li>Cientistas da EMBL compararam diretamente, pela primeira vez, o efeito de 30 medicamentos em bact\u00e9rias quando mantidas de forma isolada ou quando parte de uma comunidade complexa de bact\u00e9rias.<\/li>\r\n \t<li>Os investigadores descobriram que o impacto dos medicamentos \u00e9 geralmente menor quando as bact\u00e9rias fazem parte de uma comunidade, devido a estrat\u00e9gias de coprote\u00e7\u00e3o.<\/li>\r\n \t<li>Mapear e compreender estas intera\u00e7\u00f5es que emergem entre os medicamentos e a microbiota num contexto de comunidade poder\u00e1 ajudar cientistas a desenhar terapias melhores com menos efeitos adversos e maior efic\u00e1cia.<\/li>\r\n<\/ul><\/p>\n      <\/div>\n<\/article>\n\n\n\n\n<p>Muitos medicamentos podem inibir diretamente o crescimento ou alterar a fun\u00e7\u00e3o das bact\u00e9rias que constituem a nossa microbiota intestinal. Investigadores da EMBL em Heidelberg descobriram que este efeito de alguns medicamentos \u00e9 menor quando as bact\u00e9rias formam comunidades.<\/p>\n\n\n\n<p>Neste estudo pioneiro, cientistas pertencentes aos grupos de <a href=\"https:\/\/www.embl.org\/groups\/typas\/\">Typas<\/a>, <a href=\"https:\/\/www.embl.org\/groups\/bork\/\">Bork<\/a>, <a href=\"https:\/\/www.embl.org\/groups\/zimmermann\/\">Zimmermann<\/a> e <a href=\"https:\/\/www.embl.org\/groups\/savitski\/\">Savitski<\/a> da EMBL Heidelberg juntamente com v\u00e1rios ex-membros da EMBL incluindo <a href=\"https:\/\/www.mrc-tox.cam.ac.uk\/staff\/kiran-patil\">Kiran Patil <\/a>(Unidade de Toxicologia do MRC em Cambridge, Reino Unido), <a href=\"https:\/\/www.itqb.unl.pt\/research\/biology\/human-microbiota-xenobiotics-interactions\">Sarela Garcia-Santamarina<\/a> (ITQB, Portugal), <a href=\"https:\/\/www.umu.se\/en\/staff\/andre-mateus\/\">Andr\u00e9 Mateus<\/a> (Universidade de Ume\u00e4, Su\u00e9cia) assim como <a href=\"https:\/\/www.medizin.uni-tuebingen.de\/de\/das-klinikum\/mitarbeiter\/profil\/2110\">Lisa Maier<\/a> e <a href=\"https:\/\/www.cmfi.uni-tuebingen.de\/en\/research\/junior-research-groups\/brochado-lab\">Ana Rita Brochado<\/a> (Universidade de T\u00fcbingen, Alemanha), compararam um grande n\u00famero de intera\u00e7\u00f5es entre medicamentos e microbiota especificamente entre bact\u00e9rias mantidas em isolamento ou bact\u00e9rias mantidas numa comunidade complexa. Os resultados foram recentemente publicados na revista <a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0092867424009668?via%3Dihub\">Cell<\/a>.&nbsp;<\/p>\n\n\n\n<p>Para este estudo, a equipa investigou como \u00e9 que 30 medicamentos diferentes (incluindo aqueles que s\u00e3o direcionados para doen\u00e7as infeciosas ou n\u00e3o infeciosas) afetam 32 esp\u00e9cies de bact\u00e9rias diferentes. Estas 32 esp\u00e9cies foram escolhidas como representativas da microbiota intestinal baseado em dados dispon\u00edveis de 5 continentes.<\/p>\n\n\n\n<p>Os cientistas descobriram que, quando juntas, certas bact\u00e9rias que s\u00e3o resistentes a medicamentos t\u00eam comportamentos de comunidade o que protege bact\u00e9rias que s\u00e3o sens\u00edveis aos medicamentos. Este comportamento de \u201ccoprote\u00e7\u00e3o\u201d permite que bact\u00e9rias sens\u00edveis cres\u00e7am normalmente quando numa comunidade, mesmo que na presen\u00e7a de medicamentos que as matariam se estivessem isoladas.<\/p>\n\n\n\n<p>\u201cN\u00e3o est\u00e1vamos \u00e0 espera de tanta resist\u00eancia\u201d, diz Sarela Garcia-Santamarina, ex p\u00f3s-doutorada no grupo de investiga\u00e7\u00e3o de Typas e coprimeira autora do estudo, atualmente chefe de grupo no <a href=\"https:\/\/www.itqb.unl.pt\/\">Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica (ITQB)<\/a>, Universidade Nova de Lisboa, Portugal. \u201cFoi muito surpreendente ver que at\u00e9 metade dos casos onde bact\u00e9rias eram afetadas por medicamentos quando isoladas, n\u00e3o eram afetadas quando estavam numa comunidade\u201d.<\/p>\n\n\n\n<p>Os investigadores foram ao detalhe e estudaram o mecanismo molecular por detr\u00e1s desta coprote\u00e7\u00e3o. \u201cAs bact\u00e9rias ajudam-se entre si absorvendo ou decompondo os medicamentos\u201d, explica Michael Kuhn, investigador no grupo de Bork e coprimeiro autor deste estudo. \u201cEstas estrat\u00e9gias s\u00e3o designadas de bioacumula\u00e7\u00e3o e biotransforma\u00e7\u00e3o, respetivamente\u201d.<\/p>\n\n\n\n<p>\u201cEsta descoberta mostra que as bact\u00e9rias intestinais t\u00eam maior potencial de transformar e acumular medicamentos do que antes se pensava\u201d diz Michael Zimmermann, chefe de grupo na EMBL Heidelberg e um dos colaboradores do estudo.<\/p>\n\n\n\n<p>No entanto, h\u00e1 um limite para esta for\u00e7a da comunidade. Os investigadores viram que doses elevadas de medicamentos causam colapso das comunidades microbiotas e que as estrat\u00e9gias de coprote\u00e7\u00e3o s\u00e3o substitu\u00eddas por \u201ccosensibiliza\u00e7\u00e3o\u201d. Na cosensibiliza\u00e7\u00e3o, bact\u00e9rias que normalmente seriam resistentes a certos medicamentos tornam-se sens\u00edveis quando em comunidade \u2013 o oposto ao que os autores observaram com concentra\u00e7\u00f5es baixas de medicamentos.<\/p>\n\n\n\n<p>\u201cIsto significa que a composi\u00e7\u00e3o da comunidade permanece est\u00e1vel em concentra\u00e7\u00f5es baixas de medicamentos, uma vez que membros da comunidade protegem aqueles que s\u00e3o sens\u00edveis\u201d diz Nassos Typas, chefe de grupo na EMBL Heidelberg e autor s\u00e9nior deste estudo. \u201cNo entanto, quando a concentra\u00e7\u00e3o dos medicamentos aumenta, a situa\u00e7\u00e3o inverte. N\u00e3o s\u00f3 mais esp\u00e9cies se tornam sens\u00edveis aos medicamentos e a sua capacidade de coprote\u00e7\u00e3o diminui como intera\u00e7\u00f5es negativas surgem, o que aumenta a sensibiliza\u00e7\u00e3o da comunidade. No futuro, estamos interessados em compreender a natureza destes mecanismos de cosensibiliza\u00e7\u00e3o\u201d.<\/p>\n\n\n\n<p>Tal como as bact\u00e9rias que estudaram, tamb\u00e9m os investigadores adaptaram uma estrat\u00e9gia de comunidade para este estudo, combinando for\u00e7as cient\u00edficas. O grupo de Typas \u00e9 especializado em an\u00e1lises de larga escala associadas \u00e0 microbiota e microbiologia, enquanto que o grupo de Bork contribuiu com a sua experi\u00eancia em bioinform\u00e1tica, o grupo de Zimmermann fez estudos de metabol\u00f3mica e o grupo de Savitski fez experi\u00eancias de prote\u00f3mica. De entre os colaboradores externos, o grupo do ex-membro Kiran Patil na <a href=\"https:\/\/www.mrc-tox.cam.ac.uk\/\">Unidade de Toxicologia do Concelho de Investiga\u00e7\u00e3o M\u00e9dica (MRC)<\/a>, na Universidade de Cambridge, Reino Unido, contribuiu com a sua experi\u00eancia em intera\u00e7\u00f5es entre bact\u00e9rias intestinais e ecologia microbiana.<\/p>\n\n\n\n<p>Numa experi\u00eancia com perspetiva futura, os autores usaram o conhecimento gerado sobre as estrat\u00e9gias de coprote\u00e7\u00e3o para combinar comunidades sint\u00e9ticas que possam manter a sua composi\u00e7\u00e3o intacta ap\u00f3s tratamento com medicamentos.<\/p>\n\n\n\n<p>\u201cEste estudo \u00e9 um passo importante para a compreender como \u00e9 que os medicamentos afetam a nossa microbiota intestinal. No futuro, poderemos utilizar este conhecimento para ajustar as prescri\u00e7\u00f5es m\u00e9dicas de forma a reduzir os efeitos secund\u00e1rios dos f\u00e1rmacos\u201d diz Peer Bork, chefe de grupo e diretor da EMBL Heidelberg. &#8220;Com este objetivo em mente, estamos tamb\u00e9m a estudar como \u00e9 que intera\u00e7\u00f5es entre esp\u00e9cies s\u00e3o alteradas por nutrientes de forma a criar modelos ainda melhores que nos permitam compreender a intera\u00e7\u00e3o entre bact\u00e9rias, medicamentos e o Homem\u201d, acrescentou Patil.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>EMBL Heidelberg researchers compared the effect of drugs on isolated bacteria versus those growing in communities. This is the first study showing that bacteria are more resilient when in community due to cross-protection strategies. This could help researchers design more efficient therapies.<\/p>\n","protected":false},"author":167,"featured_media":70573,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[17591],"tags":[365,880,785,43,581,233,17693,434,582,882],"embl_taxonomy":[5152,19391],"class_list":["post-70437","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science-technology","tag-bork","tag-drug-metabolism","tag-gut-bacteria","tag-heidelberg","tag-microbiology","tag-microbiome","tag-molecular-systems-biology","tag-savitski","tag-typas","tag-zimmermann","embl_taxonomy-molecular-systems-biology","embl_taxonomy-typas-group"],"acf":{"featured":true,"show_featured_image":false,"field_target_display":"embl","field_article_language":{"value":"english","label":"English"},"article_intro":"<p>Bacteria that are sensitive to drugs can become resilient when part of communities, with the help of cross-protection strategies<\/p>\n","related_links":[{"link_description":"Typas Group","link_url":"https:\/\/www.embl.org\/groups\/typas\/"},{"link_description":"Bork Group","link_url":"https:\/\/www.embl.org\/groups\/bork\/"},{"link_description":"Savitski Group","link_url":"https:\/\/www.embl.org\/groups\/savitski\/"},{"link_description":"Zimmermann Group","link_url":"https:\/\/www.embl.org\/groups\/zimmermann\/"},{"link_description":"Fighting antimicrobial resistance with new drug combinations ","link_url":"https:\/\/www.embl.org\/news\/science\/fighting-antimicrobial-resistance-with-new-drug-combinations\/"},{"link_description":"Common medications accumulate in gut bacteria ","link_url":"https:\/\/www.embl.org\/news\/science\/medications-gut-bacteria\/"},{"link_description":"Commonly used drugs affect our gut bacteria ","link_url":"https:\/\/www.embl.org\/news\/science\/commonly-used-drugs-affect-gut-bacteria\/"},{"link_description":"The impact of drugs on gut microbes is greater than we thought ","link_url":"https:\/\/www.embl.org\/news\/science\/the-impact-of-drugs-on-gut-microbes-is-greater-than-we-thought\/"}],"source_article":[{"publication_title":"Emergence of community behaviors in the gut microbiota upon drug treatment","publication_link":{"title":"","url":"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0092867424009668?via%3Dihub","target":""},"publication_authors":"Garcia-Santamarina S., Kuhn M., et al","publication_source":"Cell","publication_date":"24 September 2024","publication_doi":"10.1016\/j.cell.2024.08.037"}],"in_this_article":false,"press_contact":"None","article_translations":[{"translation_language":"Deutsch","translation_anchor":"#german"},{"translation_language":"Portugu\u00eas","translation_anchor":"#portugu\u00eas"},{"translation_language":"Espa\u00f1ol","translation_anchor":"#spanish"}],"languages":"","vf_locked":false},"embl_taxonomy_terms":[{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"7ca3ce91-dc32-47ea-8d4b-7a53c3a3a9fd\";i:2;s:36:\"bd910dd7-0cda-4618-8bfa-d37fbda8438e\";}","parents":[],"name":["Molecular Systems Biology"],"slug":"molecular-systems-biology","description":"What &gt; 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