The impact of drugs on gut microbes is greater than we thought
From cardiometabolic drugs to antibiotics - the medication we take can
affect the human gut microbiome

Date:
December 8, 2021
Source:
European Molecular Biology Laboratory
Summary:
We are one of the most medicated generations of humans to live
on our planet. Cardiometabolic diseases like type 2 diabetes,
obesity, and coronary artery disease continue to increase in
prevalence and together constitute the highest cause of mortality
worldwide. Affected people often have to take multiple daily
medications for months or even years.

Researchers from the Bork group at EMBL Heidelberg, working together
with a European consortium involving more than twenty European
institutes, have now shown that many commonly used drugs have
powerful effects on our gut microbes. These include drugs used to
treat cardiometabolic disorders and antibiotics. The results were
published in the journal Nature.



FULL STORY ==========================================================================
We are one of the most medicated generations of humans to live on
our planet.

Cardiometabolic diseases like type 2 diabetes, obesity, and coronary
artery disease continue to increase in prevalence and together constitute
the highest cause of mortality worldwide. Affected people often have to
take multiple daily medications for months or even years.


========================================================================== Researchers from the Bork group at EMBL Heidelberg, working together with
a European consortium involving more than twenty European institutes,
have now shown that many commonly used drugs have powerful effects on
our gut microbes.

These include drugs used to treat cardiometabolic disorders and
antibiotics.

The results were published in the journal Nature.

The gut microbiome consists of billions of microorganisms essential to
the body's normal functioning.

"We analysed the effects of 28 different drugs and several drug
combinations," explained Peer Bork, Director of Scientific Activities
at EMBL Heidelberg, "Many drugs negatively impact the composition and
state of the gut bacteria, but others, including aspirin, can have
a positive influence on the gut microbiome. We found that drugs can
have a more pronounced effect on the host microbiome than disease,
diet, and smoking combined." While the negative and lasting impact of antibiotics on gut bacteria is already well-known, this study showed
that such effects likely accumulate over time.

"We found that the gut microbiome of patients taking multiple courses
of antibiotics over five years became less healthy. That included signs indicating antimicrobial resistance," said co-first author of the study
Sofia Forslund, a former postdoctoral fellow in the Bork group and now
group leader at the Max Delbru"ck Center for Molecular Medicine (MDC),
Berlin.

"We wanted to disentangle the effect that diseases have on host
microbiomes from the effect of medications, particularly in patients
taking more than one drug at the same time," said co-first author
Maria Zimmermann-Kogadeeva, group leader and former postdoc at EMBL
Heidelberg. "Being part of the MetaCardis consortium enabled us to
use multi-omics data from more than 2000 patients with cardiometabolic diseases," she added. The large cohort also allowed the researchers to establish that the dosage of drugs prescribed also has a significant
effect on the level of impact on the microbiome.

"We know that the microbiome can reflect the status of a patient's
health and provide a range of biomarkers to assess the severity of
diseases. What is often overlooked, however, is that the medication used
to treat a disease also affects the state of the microbiome," added
Rima Chakaroun, one of the lead authors of the study and a clinician
scientist at the University of Leipzig Medical Center. Dr Chakaroun is currently a postdoctoral fellow at the Wallenberg Laboratory, University
of Gothenburg.

By developing a statistical approach that accounts for the effects of
multiple confounding factors, the researchers could tease out the effects
of drugs and disease separately. "We now have a robust methodological
framework that makes it possible to get rid of many of the standard
errors," said Professor Bork.

"That allowed us to show that medication can mask the signatures of
disease and conceal potential biomarkers or therapeutic targets."
The researchers are hopeful that these results can provide knowledge
that could potentially help in drug repurposing as well as in planning individualised treatment and prevention strategies.

The study combined the insight, knowledge and approaches of experts in six countries. "It was very motivating to work with an interdisciplinary team
of clinicians, bioinformaticians, and computational systems biologists
to advance our understanding of molecular interactions in cardiometabolic disease," said Dr Zimmermann-Kogadeeva.

========================================================================== Story Source: Materials provided by
European_Molecular_Biology_Laboratory. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Sofia K. Forslund, Rima Chakaroun, Maria Zimmermann-Kogadeeva, Lajos
Marko', Judith Aron-Wisnewsky, Trine Nielsen, Lucas Moitinho-Silva,
Thomas S. B. Schmidt, Gwen Falony, Sara Vieira-Silva, Solia
Adriouch, Renato J. Alves, Karen Assmann, Jean-Philippe Bastard,
Till Birkner, Robert Caesar, Julien Chilloux, Luis Pedro Coelho,
Leopold Fezeu, Nathalie Galleron, Gerard Helft, Richard Isnard,
Boyang Ji, Michael Kuhn, Emmanuelle Le Chatelier, Antonis Myridakis,
Lisa Olsson, Nicolas Pons, Edi Prifti, Benoit Quinquis, Hugo
Roume, Joe-Elie Salem, Nataliya Sokolovska, Valentina Tremaroli,
Mireia Valles-Colomer, Christian Lewinter, Nadja B. So/ndertoft,
Helle Krogh Pedersen, Tue H. Hansen, Chloe Amouyal, Ehm Astrid
Andersson Galijatovic, Fabrizio Andreelli, Olivier Barthelemy,
Jean-Paul Batisse, Eugeni Belda, Magalie Berland, Randa Bittar,
Herve' Blottie`re, Frederic Bosquet, Rachid Boubrit, Olivier
Bourron, Mickael Camus, Dominique Cassuto, Cecile Ciangura, Jean-
Philippe Collet, Maria-Carlota Dao, Morad Djebbar, Ange'lique
Dore', Line Engelbrechtsen, Soraya Fellahi, Sebastien Fromentin,
Pilar Galan, Dominique Gauguier, Philippe Giral, Agnes Hartemann,
Bolette Hartmann, Jens Juul Holst, Malene Hornbak, Lesley Hoyles,
Jean-Sebastien Hulot, Sophie Jaqueminet, Niklas Rye Jo/rgensen,
Hanna Julienne, Johanne Justesen, Judith Kammer, Nikolaj
Krarup, Mathieu Kerneis, Jean Khemis, Ruby Kozlowski, Ve'ronique
Lejard, Florence Levenez, Lea Lucas-Martini, Robin Massey, Laura
Martinez-Gili, Nicolas Maziers, Jonathan Medina- Stamminger, Gilles
Montalescot, Sandrine Moute, Ana Luisa Neves, Michael Olanipekun,
Laetitia Pasero Le Pavin, Christine Poitou, Francoise Pousset,
Laurence Pouzoulet, Andrea Rodriguez-Martinez, Christine Rouault,
Johanne Silvain, Mathilde Svendstrup, Timothy Swartz, Thierry
Vanduyvenboden, Camille Vatier, Stefanie Walther, Jens Peter Go/tze,
Lars Ko/ber, Henrik Vestergaard, Torben Hansen, Jean-Daniel Zucker,
Serge Hercberg, Jean-Michel Oppert, Ivica Letunic, Jens Nielsen,
Fredrik Ba"ckhed, S. Dusko Ehrlich, Marc-Emmanuel Dumas, Jeroen
Raes, Oluf Pedersen, Karine Cle'ment, Michael Stumvoll, Peer
Bork. Combinatorial, additive and dose-dependent drug-microbiome
associations. Nature, 2021; DOI: 10.1038/s41586-021-04177-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211208161126.htm

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