Annual Report 2021

A year of exceptional life science research, training, service, industry collaboration, and integration of European life science research.

More than a ‘gut feeling’

From establishing new collaborations to developing innovative new approaches, EMBL researchers made great strides in their exploration of the human gut microbiome in 2021.

Illustration of a community of bacteria. Pills represent an antibiotic that can be used to treat an infection, and a second drug that could protect many gut bacteria from antibiotics.
EMBL researchers and colleagues have analysed the effects of 144 antibiotics on our most common gut microbes. Their study substantially improves our understanding of antibiotics’ effects. Credit: Isabel Romero Calvo/EMBL

The last decade clearly demonstrated how scientists  are only now beginning to appreciate the intricacies of our close relationship with the trillions of microorganisms and viruses that live on and within our body. From immunity to nutrition to behaviour, the microbiome affects us to such an extent that some compare it to a new, unexplored human organ.

In 2021, EMBL researchers united skills across disciplines, often generating new tools and methods to circumvent technical challenges that had previously stalled this field of microbiome research.

Perhaps exemplifying this approach, a study from EMBL Heidelberg’s Bork Group used metagenomics – the study of all of the genes from many different organisms in a population – to investigate the persistence and evolution of different bacteria in the human gut. By analysing the metagenomes of stool samples from over 2,000 individuals, the researchers could identify patterns in how bacterial communities changed over time and clustered in certain geographical regions.

The effect of antibiotics

Antibiotic impacts on gut flora were driven home by other EMBL studies in 2021, including one that systematically analysed the effects of 144 antibiotics on 27 of the most common gut microbes. Researchers found that two common families of antibiotics – tetracyclines and macrolides – not only stopped bacterial growth, but also killed off whole groups of bacteria, potentially leading to a more persistent, sometimes permanent, loss of these species from the gut microbiome.

However, the researchers didn’t just characterise the harmful effects of antibiotics but also investigated potential solutions. They identified several non-antibiotic drugs that could rescue gut microbes when co-administered with antibiotics, while still effectively killing the targeted pathogens. Such combination therapies may represent a leap forward towards mitigating the consequences of prolonged antibiotic exposure.

The effects of prescription drugs 

Antibiotics are not the only drugs that affect the gut microbiome, however. Using multi-omics data from more than 2,000 patients with cardiometabolic diseases, EMBL researchers and their collaborators studied the effect of commonly prescribed drugs on the gut microbiome. Surprisingly, they found drugs can affect the host microbiome more strongly than disease, diet, and smoking combined. This finding corroborated previous reports, as the gut microbiome of patients taking multiple courses of antibiotics over five years became less healthy and showed signs of antimicrobial resistance. 

Interestingly, effective drug dosage can be also influenced by microbes as drug-microbe interactions are reciprocal. Case reports have shown in the past that microbes can metabolise drugs, but now a study from the Patil, Typas, and Bork groups demonstrated for the first time the bioaccumulation of various drugs by gut microbes, affecting the bioavailability of the drugs. Bioaccumulation refers to microbes’ intracellular storage of drugs, without any type of chemical modification. Studying the effect of 15 different drugs, including antidepressants, antidiabetics, and asthma drugs on 25 selected bacterial species, the researchers discovered 70 different drug-microbe interactions, 41 of which were completely new, suggesting that many more are still to be discovered.

Illustration of two halves of a pill, which releases chemical molecules that are taken up by gut bacteria in the vicinity.
Commonly used drugs accumulate in human gut bacteria, which can affect the drugs’ effectiveness and change the bacteria’s metabolism. Credit: Aleksandra Krolik/EMBL

These results represent only a snapshot of the many advances in microbiome research EMBL achieved in 2021. Demonstrating EMBL’s collaborative spirit, the studies involved more than 20 different research institutes spread across European member states. Their collective insights may influence dietary and medical interventions, individualised treatment and prevention strategies, development of tailored probiotics, and much more. And more is yet to come. EMBL is beginning its new Programme, ‘Molecules to Ecosystems’ in 2022 with a new transversal research theme ‘Microbial Ecosystems’, which will take these investigations and others even further.

Mapping microbiomes: the power of microbial communities

Communities of microbes, known as microbiomes, are being increasingly studied by researchers around the world. EMBL researchers are contributing to this effort by characterising and analysing diverse microbial ecosystems, as well as offering automated analysis pipelines and archiving microbiome data.

Microbiome research has been and continues to be an important part of EMBL’s research portfolio.

“Looking at the parts to understand the whole is increasingly essential in microbiome research. As this has been a constant within EMBL’s approach, it’s exciting to be a part of that energy here and to see what new knowledge unfolds.”

Germana Baldi, Bioinformatician, Microbiome Informatics, EMBL-EBI

“Through combining a broad range of research areas, EMBL was pivotal to advancing the molecular understanding of drug-microbiome interactions. Few research institutions offer this level of research diversity and support”

— Kiran Patil, Director of Research at the MRC Toxicology Unit, University of Cambridge; Group Leader at EMBL, 2010–2019


Klünemann M, Andrejev S, Blasche S, Mateus A et al. (2021). Bioaccumulation of therapeutic drugs by human gut bacteria. Nature, 8 September 2021. DOI: 10.1038/s41586-021-03891

Forslund SK, Chakaroun R, Zimmermann-Kogadeeva M, Markó L, Aron-Wisnewsky J, Nielsen T et al. (2021). Combinatorial, additive and dose-dependent drug microbiome associations. Nature, 16 December 2021. DOI: 10.1038/s41586-021-04177-9

Maier L, Goemans CV et al. (2021). Unravelling the collateral damage of antibiotics on gut bacteria. Nature, 13 October 2021. DOI: 10.1038/s41586-021-03986-2

Hildebrand F et al. (2021). Dispersal strategies shape persistence and evolution of human gut bacteria. Cell Host & Microbe, 9 June 2021. DOI: 10.1016/j.chom.2021.05.008

A circular graph with many lines representing microbial species and a heat map in the background to depict sequencing information

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