A Reproducible Approach to Exploring Microbiomes todayheadline

Microbes, whether in our environment or on our bodies, exist in communities where individual members influence each other. To better understand the dynamics of these multi-species communities, researchers can grow microbes in co-culture rather than isolation. Often, co-culture setups are bespoke, and their development and validation are time and resource intensive. Also, standardization is challenging with bespoke co-culture systems, which affects collaborations and reproducibility. 

In this Innovation Spotlight, Julia Swavola, Head of Product at Cerillo, discusses the common challenges that microbial co-culture experiments present and how Cerillo’s Duet system helps scientists overcome them. 

What do researchers hope to learn from microbial co-culture experiments?

Microbes naturally exist in diverse communities. The factors impacting microbial growth within a microbiome are complex and dynamic. Researchers conduct co-culture experiments to observe and study the behavior of a microbial population within a community similar to how it would exist in nature. 

What are some major challenges related to research involving microbial populations? 

The greatest challenges in microbiome research are complexity and variability. The biology of a single cell carries enormous complexity. Studying microbes that exist in dynamic communities, influenced by the environment and other members of the community—including their host—increases that complexity exponentially. Environmental impact on phenotype and behavior can introduce variability, making meaningful conclusions difficult and collaborations between different groups, with different equipment and protocols, even more difficult.

Sequencing can tell you what is there, but not what it is doing. Microbes are like any organism, knowing what is there is only a fraction of the story. Supporting and improving the health of any ecosystem, from the rainforest to the microbiome, requires an understanding of the interactions between the members of that ecosystem. Sequencing cannot provide that understanding.

Why is standardization so important for this type of research?

Microbiome interventions hold the key to improving health, from environmental health for agriculture and coral reef preservation to gut, reproductive, and mental health. But microbiome research is difficult and complex. Many labs have freezers containing thousands of microbial populations still yet to be studied, individually and in consortia. The only way to tackle such a large and complex space is through collaboration. But with a system as dynamic and affected by small environmental changes as the microbiome, collaboration and reproducing work performed in different labs can be extremely difficult. Standardization is key, ensuring that everyone starts from the same place and enables collaborators to analyze data through the same lens.

How does the Duet co-culture system work and what are its benefits? 

Designed by researchers for researchers, Duet addresses the pain points of traditional systems, delivering new capabilities that make co-culture studies easier, faster, and more reproducible. Duet fundamentally changes how researchers approach co-culture experiments in several ways. 

For example, unlike Transwell® systems, Duet enables real-time quantitative analysis of both cell populations. Its compatibility with plate readers and other assays allows researchers to gather dynamic data throughout an experiment. Duet is optimized for automation, making it compatible with liquid handlers and high-throughput workflows. Media changes, sampling, and assay setup become faster and more reliable. 

The current method for collecting quantitative data on population dynamics is with assays involving plating. Compared to plating, the data that is collected through Duet liquid cultures is an order of magnitude more precise, studying liquid culture instead of colony counting makes data available one to two days sooner, data is recorded dynamically and automatically rather than by plate counting, and it is less expensive because the system does not rely on agar plates. 

Duet’s horizontally oriented reservoirs eliminate the sloshing and contamination risks associated with vertical setups where Transwells are manually handled and inserted into open plate wells. The Duet design makes pipetting faster and easier and does not require manual handling, which minimizes the risk of contamination and ensures consistency even during large-scale studies. Finally, the vertically oriented permeable membrane is sturdy enough to handle routine manipulations without tearing, reducing experiment loss due to accidental damage. 

How does this system solve some of the problems related to microbial population research?

Duet is not just a refinement of existing tools—it is opening new possibilities for microbial and cellular interaction studies. Researchers are already using Duet to investigate microbial dynamics with greater precision, including studies of antimicrobial resistance and interactions between co-cultured species. Its design allows for deeper insights into how microbes positively cooperate or negatively compete, critical for understanding microbial community functions. 

What are some of the most exciting avenues of research being conducted with this system?

Scientists have used the Duet co-culture system to study enormously diverse and exciting applications from antibiotics for antimicrobial resistant microbes and minimum inhibitory drug concentration to lytic microbial interactions and pulmonary, gut, and women’s health. We even have researchers using Duet co-culture to study struvite kidney stone formation and growth dynamics of the gut microbiome in preterm babies and their response to breast milk components.

The system has also proven valuable in mammalian cell research. For example, its ease of use and scalability are ideal for studying cellular communication or high-throughput screening of potential therapeutic compounds. The ability to collect real-time data from both sides of the membrane enhances experiment reliability and accelerates discovery. 

What do you think is the next frontier for research involving microbial interactions?

Microbes must be studied phenotypically and in consortia. Companies developing therapeutics or microbiome-based products that understand and embrace the challenge of studying microbes in their native state have made incredibly exciting developments. As scientists unlock the tools to embrace the complexity of microbial research and empower collaborations, their ability to understand and improve the health of people, communities, and the planet is endless.