Microbiology Mystery: Why Do Most Microbes Die in Labs?

A new study reveals that microbial diversity is shaped by a network of mutual dependencies.

Microbial ecosystems are found all around us—in seawater, soil, and even inside the human gut—and they are bursting with an incredible variety of life. Yet, scientists have long faced a frustrating challenge: trying to recreate this rich diversity in the lab. Many microbes simply die when researchers attempt to grow them outside their natural environment.

Now, a new study from the Helmholtz Institute for Functional Marine Biodiversity at the University of Oldenburg (HIFMB) in Germany is offering a fresh perspective on why this happens. The research suggests that microbial survival isn’t just about individual species and what they need. Instead, it depends on a hidden web of interconnections among microbes. Even small disruptions to these relationships can cause the entire system to fall apart.

The study, published in the journal PNAS, was led by biodiversity experts Dr. Thomas Clegg and Professor Thilo Gross. They approached microbial communities as intricate networks built on “cross-feeding,” where microbes exchange metabolic by-products with one another. Each species takes in nutrients while releasing substances that serve as essential food for others.

To explore this complex system, Clegg and Gross used a unique approach. They applied network theory, a branch of mathematics originally developed in physics to understand how complicated systems behave.

Fragile Networks and Tipping Points

The result of the analysis: in the model, the loss of individual populations can cause the entire network to collapse, with the microbial community transitioning abruptly to a state of lower diversity. “These collapses act as tipping points, resembling blackouts in power grids or supply chain breakdowns seen during the COVID-19 pandemic,” explains lead author Clegg.

Trying to grow a microbial community in the laboratory is an example of such a perturbation, according to the researchers. For example, if not all members of a natural microbial community are included in a sample, they will be missing as producers of metabolic products that are vital for other species. “By focusing on the structure of these interactions, the study offers new insight into why diversity is so hard to maintain in a lab setting,” explains Thilo Gross.

Although researchers have long suspected that the dependencies between microbes play a key role in our ability to grow them, this study is the first to show how this works across whole communities. The findings offer a new perspective on microbial resilience, highlighting how even in resource-rich environments like lab cultures, communities can fail if the networks of relationships are disrupted. Crucially, the model also reveals that once a community collapses, recovery can be difficult, even when resources are reintroduced.

“It’s not just about what individual microbes need, but who they depend on,” says lead author Dr. Tom Clegg “the whole community thrives, or collapses, together.”

Reference: “Cross-feeding creates tipping points in microbiome diversity” by Tom Clegg and Thilo Gross, 6 May 2025, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2425603122

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