{"id":41938,"date":"2021-09-08T17:00:00","date_gmt":"2021-09-08T15:00:00","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=41938"},"modified":"2024-03-22T11:26:45","modified_gmt":"2024-03-22T10:26:45","slug":"medications-gut-bacteria","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/medications-gut-bacteria\/","title":{"rendered":"Common medications accumulate in gut bacteria"},"content":{"rendered":"\n

Common medications can accumulate in gut bacteria, a new study has found, altering bacterial function and potentially reducing the effectiveness of the drug. These interactions \u2013 seen for a variety of medications, such as depression, diabetes, and asthma drugs \u2013 could help researchers to better understand individual differences in drug effectiveness and side-effects, according to the study published in Nature<\/em>.<\/p>\n\n\n\n

It is known that bacteria can chemically modify some drugs, a process known as biotransformation. This study, led by researchers from the Medical Research Council (MRC) Toxicology Unit at the University of Cambridge and the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, is the first to show that certain species of gut bacteria accumulate human drugs, altering the types of bacteria and their activity.<\/p>\n\n\n\n

This could change the effectiveness of the drug both directly, as the accumulation could reduce the availability of the drug to the body, and indirectly, as altered bacterial function and composition could be linked to side-effects.<\/p>\n\n\n\n

The human gut naturally contains communities of hundreds of different species of bacteria, which are important in health and disease, called the gut microbiome. The composition of bacterial species varies significantly between people and has previously been shown to be associated with a wide range of conditions including obesity, immune response, and mental health.<\/p>\n\n\n\n

In this study, the researchers grew 25 common gut bacteria and studied how they interacted with 15 drugs that are taken orally. The drugs were chosen to represent a range of different types of common drugs, including antidepressant medications, which are known to affect individuals dissimilarly and cause side effects such as gut problems and weight gain.<\/p>\n\n\n\n

The researchers tested how each of the 15 drugs interacted with the selected bacterial strains \u2013 a total of 375 bacteria\u2013drug tests. They found 70 interactions between the bacteria and the drugs studied \u2013 of which 29 had not been previously reported.<\/p>\n\n\n\n

While earlier research has shown bacteria can chemically modify drugs, when the scientists studied these interactions further, they found that for 17 of the 29 new interactions, the drug accumulated within the bacteria without being modified.<\/p>\n\n\n\n

Kiran Patil, outgoing EMBL Group Leader who\u2019s now based at the MRC Toxicology Unit at the University of Cambridge, who co-led the study, said: \u201cIt was surprising that the majority of the new interactions we saw between bacteria and drugs were the drugs accumulating in the bacteria, because up until now biotransformation was thought to be the main way that bacteria affect the availability of drugs.\u201d<\/p>\n\n\n\n

\u201cThere will likely be very personal differences between individuals, depending on the composition of their gut microbiota. We saw differences even between different strains of the same species of bacteria,\u201d Dr Patil added.<\/p>\n\n\n\n

Examples of drugs that accumulated in bacteria include antidepressant duloxetine and anti-diabetic rosiglitazone. For some drugs, such as montelukast (an asthma drug) and roflumilast (for chronic obstructive pulmonary disease), both changes happened in different bacteria \u2013 they were accumulated by some species of bacteria and modified by others.<\/p>\n\n\n\n

The scientists also found that the bioaccumulation of drugs alters the metabolism of the accumulating bacteria. For example, the antidepressant drug duloxetine bound to several metabolic enzymes within the bacteria and altered their secreted metabolites.<\/p>\n\n\n\n

The researchers grew a small community of several bacterial species together and found the antidepressant duloxetine dramatically altered the balance of bacterial species. The drug altered the molecules produced by the drug-accumulating bacteria, which other bacteria feed on, so the consuming bacteria grew much more and unbalanced the community composition.<\/p>\n\n\n\n

The researchers tested the effects further using C. elegans<\/em>, a nematode worm commonly used to study gut bacteria. They studied duloxetine, which had been shown to accumulate in certain bacteria but not others. In worms grown with the species of bacteria that had been shown to accumulate the drug, the behaviour of the worms was altered after being exposed to duloxetine, compared with worms that were grown with bacteria that did not accumulate duloxetine.<\/p>\n\n\n\n

The study had been started as a collaborative project at EMBL Heidelberg and was concluded in the group of Kiran Patil after his move to Cambridge. It involved researchers from EMBL\u2019s Typas, Bork, Zimmermann, Hennig, Schultz, and Beck groups and Savitski team, as well as the Genomics, Proteomics, and Metabolomics Core Facilities at EMBL Heidelberg.<\/p>\n\n\n\n

Nassos Typas, Group Leader and Senior Scientist at EMBL Heidelberg, who co-led the study, said: \u201cOnly now people are recognising that drugs and our microbiome impact each other with a critical consequence to our health.\u201d Peer Bork, Director of EMBL Heidelberg (Scientific Activities) and a co-lead of the study added: \u201cThis calls for us to start treating the microbiome as one of our organs.\u201d<\/p>\n\n\n\n

Dr Megan Dowie, <\/strong>Head of Molecular and Cellular Medicine at the MRC, said: \u201cThis study highlights the importance of the microbiome in drug delivery, effectiveness and safety. There\u2019s still a great deal that is not well understood about the microbiome and it\u2019s clear that further work needs to be done to understand the important molecular aspects involved here, which could lead to a positive impact on an individual\u2019s response to a range of commonly used drugs.\u201d<\/p>\n\n\n\n

Dr Patil concluded: \u201cNext steps for us will be to take forward this basic molecular research and investigate how an individual\u2019s gut bacteria tie with the differing individual responses to drugs such as antidepressants \u2013 differences in whether you respond, the drug dose needed, and side effects like weight gain. If we can characterise how people respond depending on the composition of their microbiome, then drug treatments could be individualised.\u201d<\/p>\n\n\n\n

The researchers caution that the study findings are only on bacteria grown in the lab and more research is needed to understand how bioaccumulation of medications by gut bacteria manifests inside the human body. The study was funded by the European Commission Horizon 2020, MRC and EMBL.<\/p>\n\n\n\n

This article is a joint press release<\/a> with the MRC Toxicology Unit at the University of Cambridge, UK.<\/p>\n","protected":false},"excerpt":{"rendered":"

A new collaborative study led by EMBL group leaders Kiran Patil, Nassos Typas, and Peer Bork has found that common medications accumulate in human gut bacteria. This process reduces drug effectiveness and affects the metabolism of common gut microbes, thereby altering the gut microbiome.<\/p>\n","protected":false},"author":16,"featured_media":41954,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[580,350,365,474,227,981,880,1704,42,579,43,729,786,219,5776,233,466,45,434,383,76,582,882],"embl_taxonomy":[19179,9796,5146,3744,19283,3746,5152,3750,19371,19391,19417],"class_list":["post-41938","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-bacteria","tag-beck","tag-bork","tag-collaboration","tag-core-facility","tag-drug","tag-drug-metabolism","tag-embl-programme","tag-genomics","tag-gut","tag-heidelberg","tag-hennig","tag-human-microbiome","tag-metabolomics","tag-microbial-ecosystems","tag-microbiome","tag-patil","tag-proteomics","tag-savitski","tag-schultz","tag-service","tag-typas","tag-zimmermann","embl_taxonomy-bork-group","embl_taxonomy-embl-heidelberg","embl_taxonomy-genome-biology","embl_taxonomy-genomics-core-facility","embl_taxonomy-hennig-group-visiting","embl_taxonomy-metabolomics-core-facility","embl_taxonomy-molecular-systems-biology","embl_taxonomy-proteomics-core-facility","embl_taxonomy-savitski-team","embl_taxonomy-typas-group","embl_taxonomy-zimmermann-group"],"acf":{"featured":true,"show_featured_image":false,"article_intro":"

Drug accumulation may reduce drug effectiveness and alter the gut microbiome<\/p>\n","related_links":[{"link_description":"Research in the Patil Group","link_url":"https:\/\/www.embl.org\/groups\/patil\/"},{"link_description":"Research in the Typas Group","link_url":"https:\/\/www.embl.org\/groups\/typas\/"},{"link_description":"Research in the Bork Group","link_url":"https:\/\/www.embl.org\/groups\/bork\/"},{"link_description":"Structural and Computational Biology Unit","link_url":"https:\/\/www.embl.org\/research\/units\/structural-and-computational-biology\/"},{"link_description":"Genome Biology Unit","link_url":"https:\/\/www.embl.org\/research\/units\/genome-biology\/"},{"link_description":"EMBL\u2019s Scientific Services","link_url":"https:\/\/www.embl.org\/services-facilities\/"},{"link_description":"Genomics Core Facility","link_url":"https:\/\/www.embl.org\/groups\/genomics\/"},{"link_description":"Metabolomics Core 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