Microorganisms are not just limited to causing infections in mammals; in fact, healthy humans and animals host billions of microbes at any given moment. These microbes communicate through chemical signals, influencing overall health. Recently, researchers investigated the microbiome—the complete collection of microorganisms—in both humans and animals in zoos. Their goal was to discover new approaches for diagnosing and treating diseases.
Microorganisms are not merely infectious agents in mammals. Healthy humans and animals harbor billions of microbes at all times, which communicate through chemical signals that can affect their health. In two detailed studies, researchers from the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), along with Saarland University and Saarland University Hospital, conducted a thorough exploration of the microbiome—comprising all microorganisms—found in humans and zoo animals. Their primary aim was to find new techniques for treating and diagnosing various diseases.
The findings are published in two studies in the journal Nature Communications. HIPS is a part of the Helmholtz Centre for Infection Research (HZI), collaborating with Saarland University.
The concept of utilizing microorganisms as sources for novel medicinal compounds is not novel. Many medications have previously been derived from natural products produced by fungi and bacteria. These microorganisms compete for nutrients in their natural surroundings, such as soil, and utilize chemical signals to gain advantages over rivals. Consequently, it’s not surprising that a significant portion of commercially available antibiotics stem from compounds found in microorganisms. A collaborative team at HIPS, Saarland University, and Saarland University Hospital aims to discover natural products for the treatment of non-infectious ailments as well. Instead of searching through soil, they are looking directly into bacteria found in humans and animals that may play a role in the onset of diseases. This strategy is also a vital part of the nextAID³ cluster of excellence initiative, which received positive evaluations in an initial review by the German Research Foundation (DFG), and for which a comprehensive proposal was submitted by Saarland University in August 2024.
For this extensive search, the researchers relied on two cohorts. In the “IMAGINE” study, nearly 2,000 samples were gathered from healthy individuals and patients suffering from various conditions. Since different diseases can affect various facets of the microbiome, the team examined microbiome samples from saliva, dental plaque, feces, and from areas like the eye, throat, and skin. In a second, smaller study, they analyzed the microbiome of zoo animals in Saarbrücken, contrasting it with that of wild animals. This study aimed to demonstrate that animal microbiomes could also serve as a valuable source for new natural products. The specimens gathered from both studies underwent metagenome sequencing, a process that enables the genetic identification of all organisms in a sample along with their abundance. Identifying variations in bacterial strains related to specific diseases could suggest potential links to disease development or progression.
The research team, which included bioinformatician Andreas Keller, microbiologist Sören Becker, pulmonologist Robert Bals, and pharmacist Rolf Müller, discovered numerous bacterial strains exhibiting such associations in their analysis. Through bioinformatics assessments, they also pinpointed genetic blueprints (known as biosynthesis gene clusters) of natural products related to the examined diseases. “This data is an invaluable scientific resource. We still lack clarity on the natural products that most of the newly identified gene clusters encode,” stated Andreas Keller, head of the department at HIPS and Professor of Clinical Bioinformatics at Saarland University. “The data we collected is now being organized in our newly developed database, ABC-HuMi, which compiles additional information on the human microbiota, paving the way for discovering many new natural products that could inform drug development.”
The pharmacists, biologists, and chemists at HIPS are now tasked with transforming this data into tangible natural products. Currently, six research groups are working to experimentally validate the 50 most promising gene clusters. “Understanding the genetic blueprint for a natural product is only the initial step. We are diligently working to introduce these blueprints into bacteria that will then synthesize the respective natural products,” explained Rolf Müller, department head and scientific director at HIPS, who co-initiated the studies. “The gathered data reflects an incredible diversity that has yet to be investigated thoroughly. Our next move will be to leverage this potential. We are excited to apply the technologies we’ve honed over the past 15 years for antibiotic development to other areas as well.”
While HIPS primarily focuses on antimicrobial agents, therapies for non-infectious conditions will be developed through the PharmaScienceHub. This collaborative platform, established between HIPS and Saarland University in 2023, unites academic and pharmaceutical industry stakeholders to fast-track the translation of fundamental research into clinical applications.
