The latest results in microbiome research are speaking loud and clear: bacterial-based products are becoming increasingly effective and optimised when multiple strains are combined within a single formulation. In response to this trend, the future of CDMOs lies in adapting to these evolving needs while making the best possible use of available resources. At Biose, we have leveraged our expertise to stay abreast of the latest technologies, and we are proud to present our new service for multi-strain manufacturing processes: co-culture.
Written by:
Nadine Daou, VP of US Operations
Taous Saraoui-Mazed, Head of Programs
What does co-culturing mean?
It refers to the joint fermentation of multiple bacterial strains within the same manufacturing workflow, as opposed to the classical protocol of growing each strain in individual monocultures and blending only at the end.
So why would a company working with bacterial products consider co-culture?
As microbiome products become more sophisticated, manufacturing is being pushed far beyond the single-strain model. Many live biotherapeutic products (LBPs) and next-generation probiotics (NGPs) no longer rely on one isolated microorganism, but on combinations of strains designed to work together. Following that trend, microbiome-related basic research is evolving towards defining bacterial consortia that maximise the potential benefits, all while keeping unsought bacteria out of the mix.
As a result, developers look for manufacturing strategies that can handle this growing level of formulation complexity without multiplying operational burden. In that context, co-culture has emerged as a valuable approach, allowing multiple strains to be grown within the same process in order to streamline development and help reduce manufacturing costs.
As a result, co-culture can be, if designed properly, a strategic tool to reduce manufacturing load, support product affordability, and even take advantage of the natural metabolic interactions between strains.
Challenges of co-culture techniques
➢ Nutrient competition. When several bacterial strains compete for available nutrients, they often proliferate in unequal proportions. Natural behaviours and competing principles operate, allowing only the strongest to grow and limiting the others.
➢ Differences in nutrient needs. If the media composition is not optimally designed, one strain may proliferate faster than the others, all while the rest lag because the medium does not fully support its own requirements. That would lead to one strain dominating the culture, therefore losing the intended proportion.
➢ Growth conditions. When manufacturing bacterial products, adjusting environmental conditions to maximise growth and production is essential. However, when combining more than one taxon, choosing an environmental combination that maximises the growth of all strains becomes a far more difficult task.
This combination of variables means that a successful co-culture depends on a deep understanding of each strain’s physiology: which nutrients it prefers, which metabolites it produces, which environmental conditions it tolerates, and how it is likely to behave in the presence of other strains.
It also means that the wrong manufacturing partner can turn complexity into variability very quickly. For companies developing multi-strain LBPs or NGPs, choosing a CDMO with real strain knowledge becomes a risk-management decision.
Biose’s co-culture workflow
Biose approaches co-culture leveraging their deep microbial knowledge acquired through their 8+ years of experience as a leading CDMO in bacterial products. Rather than treating mixed fermentation as a slightly different manufacturing protocol, Biose’s pipeline starts with understanding the individual strains to assess their growth conditions, media requirements, and critical process parameters. That previous expertise, built through years of work in live biotherapeutics and advanced microbial products, provides the basis for designing rational co-culture strategies.
From there, development moves stepwise. The experts at Biose study each strain’s metabolic behaviour in detail, mapping the nutrients it consumes, the compounds it releases, and the ways those compounds can be used by other members of the consortium. This allows the team to identify bacterial combinations in which the metabolic output of one strain becomes a useful input for another, creating linked growth-supporting interactions within the culture.
Rather than functioning as isolated organisms competing for the same limited resources, the strains can be selected to operate as an interconnected system that uses the medium more efficiently. This type of metabolite-sharing interaction is known as cross-feeding, and it is one of the key mechanisms Biose leverages to design smarter, more efficient, and more cost-effective co-culture processes.
Once the compatible strains have been grouped, the growth medium is adjusted to support different metabolic needs, and process conditions are tested to identify which variables may shift the balance of the population. This is particularly important in the context of co-culture because, far from just growing bacteria, the challenge is to grow the right bacteria, in the right proportions, under conditions that remain stable and scalable.
Analytical control is another decisive factor. In a mixed fermentation, standard colony-forming unit (CFU) plating may provide a total count, but it does not offer enough visibility at the strain level. For multi-strain products, that is a major limitation. Biose addresses this by using highly specific quantitative methods (qPCR-based analytical strategies) that allow teams to monitor the behaviour of individual strains within the culture. That means being able to track whether populations remain balanced over time, whether one strain is taking over, and how process changes affect the final microbial composition. For complex microbiome products, that level of monitoring is essential.
Benefits of using co-culture
For developers working with multi-strain formulations, running one separate fermentation per strain can rapidly increase cost and operational burden. A well-designed co-culture strategy can significantly reduce that burden by consolidating compatible strains into fewer fermentation workflows while maintaining control over the process. For companies targeting broader accessibility or cost-sensitive markets, this can have a direct commercial impact.
Co-culture also offers a compelling approach to designing complex but controlled microbial products. In contrast to donor-derived approaches such as faecal microbiota products, co-culture allows developers to build products with intentional microbial complexity while preserving greater control over which strains are present. For companies operating in the microbiome space, that distinction is becoming increasingly important, as the future belongs to complex, controlled formulations.
Biose’s experience positions it as a development partner capable of turning microbial complexity into a robust, industrially viable product strategy.
The science is demanding, and the market is moving fast. Choose a partner who can keep up with the pace.
