New study, lead by David Gomez Varela and Manuela Schmidt, published in Nature Communications

 

A team led by scientists of the Center of Excellence for Metaproteomics and the Systems Biology of Pain Laboratory from the University of Vienna has developed uMetaP, a next-generation workflow that boosts the sensitivity of gut metaproteomics by up to 5,000-fold. This breakthrough uncovers previously undetectable host–microbiome interactions and points to new therapeutic targets for inflammatory bowel diseases. In addition to shedding light on disease mechanisms, the approach points to both existing treatments and novel drug candidates, opening new avenues for therapeutic interventions. The study was recently published in Nature Communications.

Shining light on the "dark metaproteome"

A substantial portion of gut microbial activity—often referred to as the “dark metaproteome”—has remained invisible to science. Traditional metaproteomic approaches struggle to capture proteins from low-abundance organisms, many of which play critical yet underappreciated roles in shaping microbial ecosystems and influencing host health.

uMetaP addresses this sensitivity gap by combining state-of-the-art mass spectrometry (timsTOF Ultra with DIA-PASEF) and novoMP, a purpose-built de novo sequencing pipeline designed to rigorously control false discoveries in complex spectral landscapes.

By going beyond conventional database searches and harnessing the full depth of available data from mass spectrometry analyses, uMetaP expands both taxonomic detection and functional annotation, capturing protein-level signals from bacteria, archaea, fungi, viruses, and host tissues that were previously undetectable. Feng Xian, first author of the paper, explains: "Our new sequencing pipeline provides enhanced visibility of these organisms. It opens the door to studying underappreciated microbial players and their contributions to health and disease at an unprecedented resolution."

 

Record sensitivity: down to parts-per-million microbial signals

To evaluate the detection limits in a realistic setting, the team conducted controlled "spike-in" experiments by adding two stable isotope-labeled bacterial colonies (Ligilactobacillus murinus and exogenous Salinibacter ruber) to mouse fecal samples. uMetaP successfully detected as few as 10,000 bacterial cells per 10 mg of feces, a detection threshold in the parts-per-million range relative to an estimated 10 billion native gut microbes. This level of performance marks a major step forward for metaproteomics, enabling the detection of rare microbial signatures that may disproportionately influence host–microbiome dynamics and diseases.

 

From mice with gut injuries to relevance for human diseases

Applying uMetaP to a transgenic mouse model with a colonic injury driven by mitochondrial dysfunction, researchers tracked changes in the microbiome and the hosts responses over time. They captured an early and pronounced increase in Bacteroides caecimuris and mapped microbial metabolic pathways linked to the injury. Comparative analysis of the mouse data with Crohn’s disease patient transcriptomes revealed hundreds of overlapping molecules, strengthening the relevance of the findings to human diseases and reinforcing uMetaP’s potential in bridging experimental and clinical research.

 

Scientific Contact:

David Gomez Varela PhD

Center of Excellence for Metaproteomics University of Vienna - Bruker Daltonics

Division of Pharmacology & Toxicology
Department of Pharmaceutical Sciences
1090, Josef-Holaubek-Platz 2 (UZA II)
+43-1-4277-55361
david.gomez.varela@univie.ac.at

 

  

An ionization spray from a mass spectrometer, symbolized by the light beam, illuminates the dark metaproteome to reveal host-microbe interactions in a mouse model of intestinal disease.

The University of Vienna opens the Center of Excellence for Metaproteomics in collaboration with Bruker

Fig. 1: From left to right: David Gómez-Varela, Torsten Mueller und Ronald Maier. C: Alexander Bachmayer

New cooperation combines cutting-edge research with state-of-the-art technology.

The new Center of Excellence for Metaproteomics at the University of Vienna will focus on microbiome research using high-resolution protein-based methods. The strategic partnership between the University of Vienna and Bruker combines cutting-edge research with state-of-the-art technology. The new Center of Excellence for Metaproteomics will be headed by biochemist David Gómez-Varela from the University of Vienna.

The microbiome plays a crucial role in diverse ecosystems including human health and disease. David Gómez-Varela and Manuela Schmidt from the Department of Pharmaceutical Sciences at the University of Vienna have developed innovative methods in the field of metaproteomics. Metaproteomics includes experimental approaches for the investigation of proteins (the entire set of proteins is called the proteome) of microbial communities in living organisms and environmental sources. This facilitates the analysis of changes in the proteome of both microorganisms and their host. For example, metaproteomics can be used to study the microbiome of the human gut and, in parallel, the human gut cells themselves. The unique advantage of this post-genomic method is that it enables scientists not only to understand which microorganisms are present in a sample, but also how they work and interact with each other. Consequently, deeper insights into the microbiome and its functions can be gained promising significant advances in the fields of healthy ageing, personalized medicine, and disease prevention.

As a manufacturer of scientific instruments for molecular and material-based research, Bruker is an important strategic partner. The company has established cooperations with top research institutions in so-called Centers of Excellence.
In the new Center of Excellence for Metaproteomics, scientists from the University of Vienna and experts from Bruker will work side by side to develop highly sensitive methods for studying the microbiome.

"We welcome this new collaboration, in which the University of Vienna and the manufacturer Bruker combine cutting-edge research with state-of-the-art technology. The ultimate goal is to generate new knowledge about the microbiome to improve human health," says Ronald Maier, Vice Rector for Digitalization and Knowledge Transfer at the University of Vienna.

"This partnership with Bruker is a great opportunity. Bruker's leading position in developing cutting-edge technologies to decode proteins, i.e. the functional language of all living organisms, will significantly advance our research. Together, we aim to use metaproteomics to diagnose and predict diseases, improve the efficacy of therapies, and develop new biotechnological tools for biomedical applications," says David Gómez-Varela, Director of the newly established Center of Excellence for Metaproteomics.

"We are delighted to establish a long-term collaboration with the University of Vienna, and, in particular, with David Gómez-Varela and Manuela Schmidt, to realize our shared vision of using metaproteomics to understand biology, improve health, and treat disease," says Rohan Thakur, President of the Life Science Mass Spectrometry Division at Bruker. "Together, this partnership will foster a dynamic and collaborative environment for biomedical research in Vienna."